A clinical study conducted in India and published in the peer reviewed journal Food & Nutrition Research reported that adults with irritable bowel syndrome (IBS) showed improvement from co-existing depression when they took a probiotic strain Bacillus coagulans MTCC 5856 (2 billion spores per day); subjects of the study given a placebo did not report the same improvement.
This study, Bacillus coagulans MTCC 5856 for the management of major depression with irritable bowel syndrome: a randomised, double blind, placebo controlled, multi-centre, pilot clinical study, published in Food & Nutrition Research, provides evidence of clinical efficacy of B. coagulans MTCC 5856 in patients experiencing major depression symptoms with IBS and supports the hypothesis that the modification of microbial ecology in human gut by supplementing probiotics may be an alternative strategy to ameliorate or prevent depression. The study demonstrates that consumption of probiotic B. coagulans MTCC 5856 may improve gut symptoms and psychological issues i.e. major depression, sleeplessness, and dementia in IBS. This provides new opportunity not only to help patients suffering from gastrointestinal related disorders but also the patients suffering from extra-intestinal disorders such as major depression, quality of sleep and dementia.
IBS is characterized by the alterations in bowel function or discomfort, abdominal pain or bloating and diarrhea or constipation, with the prevalence estimated between 9% and 23% in the population across the world. IBS patients are also frequently affected by chronic anxiety, mood disorders and major depression.
This 90 day randomized, double blind, placebo controlled trial involved 40 adults with IBS co-existing with major depressive disorder. Twenty participants took a daily dose of the probiotic B. coagulans MTCC 5856 (2 billion spores per day) and other 20 subjects were on placebo. At 90 days, subjects receiving B. coagulans MTCC 5856 (2 × 109 spores/day) reported a significant change/decrease in their depression clinical symptoms along with decrease in IBS as compared to subjects receiving placebo. It was also noticed that the subjects in the B. coagulans MTCC 5856 group reported improvement in sleeplessness and to a lesser extent for dementia.
The study reported no clinically significant changes in vital signs, no abnormal lab values (biochemistry and hematology), and also no Serious Adverse Events or Significant Adverse Events associated with the consumption of probiotic B. coagulans MTCC 5856, suggesting its excellent clinical safety in patients suffering from major depression with IBS.
These clinical findings indicate that B. coagulans MTCC 5856 may be an important new treatment option for major depressive disorder in IBS patients and opens a new avenue for the probiotic use in gut and psychological conditions.
Sabinsa undertook this study after Shaheen Majeed, President-worldwide, noticed depression to be commonly reported among subjects suffering from IBS at the time of screening for the first clinical trial conducted on LactoSpore® for the treatment of IBS predominant diarrhea and those patients were excluded in the study (Majeed et al. 2016.
Original Research: “Bacillus coagulans MTCC 5856 for the management of major depression with irritable bowel syndrome: a randomised, double blind, placebo controlled, multi-centre, pilot clinical study”

Background: The modification of microbial ecology in human gut by supplementing probiotics may be an alternative strategy to ameliorate or prevent depression.
Objective: The current study was conducted to assess the safety and efficacy of the probiotic strain Bacillus coagulans MTCC 5856 for major depressive disorder (MDD) in IBS patients.
Method: Patients (n = 40) diagnosed for MDD with IBS were randomized (1:1) to receive placebo or B. coagulans MTCC 5856 at a daily dose of 2 × 109 cfu (2 billion spores) and were maintained to the end of double-blind treatment (90 days). Changes from baseline in clinical symptoms of MDD and IBS were evaluated through questionnaires.
Results: Significant change (p = 0.01) in favour of the B. coagulans MTCC 5856 was observed for the primary efficacy measure Hamilton Rating Scale for Depression (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Center for Epidemiological Studies Depression Scale (CES-D) and Irritable bowel syndrome quality of life questionnaire (IBS-QOL). Secondary efficacy measures i.e. Clinical Global Impression-Improvement rating Scale (CGI-I), Clinical Global Impression Severity rating Scale (CGI-S), Gastrointestinal Discomfort Questionnaire (GI-DQ) and Modified Epworth Sleepiness Scale (mESS) also showed significant results (p = 0.01) in B. coagulans MTCC 5856 group compared to placebo group except dementia total reaction scoring. Serum myeloperoxidase, an inflammatory biomarker was also significantly reduced (p max 0.01) when compared with the baseline and end of the study. All the safety parameters remained well within the normal clinical range and had no clinically significant difference between the screening and at the end of the study.
Conclusion: B. coagulans MTCC 5856 showed robust efficacy for the treatment of patients experiencing IBS symptoms with major depressive disorder. The improvement in depression and IBS symptoms was statistically significant and clinically meaningful. These findings support B. coagulans MTCC 5856 as an important new treatment option for major depressive disorder in IBS patients. Trial Registration: Clinical Trials Registry India Identifier: CTRI/2015/05/005754 Keywords: probiotic; B. coagulans MTCC 5856; LactoSpore®; major depression; irritable bowel syndrome
Bacillus coagulans MTCC 5856 for the management of major depression with irritable bowel syndrome: a randomised, doubleblind, placebo controlled, multi-centre, pilot clinical study - Muhammed Majeed1,Kalyanam Nagabhushanam, Sivakumar Arumugam, Shaheen Majeed and Furqan Ali

Background: Bacillus coagulans MTCC 5856 has been marketed as a dietary ingredient, but its efficacy in diarrhea predominant irritable bowel syndrome (IBS) condition has not been clinically elucidated till date. Thus, a double blind placebo controlled multi-centered trial was planned to evaluate the safety and efficacy of B. coagulans MTCC 5856 in diarrhea predominant IBS patients.
Methods: Thirty six newly diagnosed diarrhea predominant IBS patients were enrolled in three clinical centres. Along with standard care of treatment, 18 patients in group one received placebo while in group two 18 patients received B. coagulans MTCC 5856 tablet containing 2 × 109 cfu/day as active for 90 days. Clinical symptoms of IBS were considered as primary end point measures and were evaluated through questionnaires. The visual analog scale (VAS) was used for abdominal pain. Physician’s global assessment and IBS quality of life were considered as secondary efficacy measures and were monitored through questionnaires.
Results: Laboratory parameters, anthropometric and vital signs were within the normal clinical range during the 90 days of supplementation in placebo and B. coagulans MTCC 5856 group. There was a significant decrease in the clinical symptoms like bloating, vomiting, diarrhea, abdominal pain and stool frequency in a patient group receiving B. coagulans MTCC 5856 when compared to placebo group (p < 0.01). Similarly, disease severity also decreased and the quality of life increased in the patient group receiving B. coagulans MTCC 5856 when compared to placebo group.
Conclusions: The study concluded that the B. coagulans MTCC 5856 at a dose of 2 × 109 cfu/day along with standard care of treatment was found to be safe and effective in diarrhea predominant IBS patients for 90 days of supplementation. Hence, B. coagulans MTCC 5856 could be a potential agent in the management of diarrhea predominant IBS patients.
Keywords: Lactobacillus, Bacillus coagulans, LactoSpore®, Diarrhea, Irritable Bowel Syndrome
Bacillus coagulans MTCC 5856 supplementation in the management of diarrhea predominant Irritable Bowel Syndrome: a double blind randomized placebo controlled pilot clinical study - Muhammed Majeed1, Kalyanam Nagabhushanam, Sankaran Natarajan, Arumugam Sivakumar, Furqan Ali, Anurag Pande, Shaheen Majeed and Suresh Kumar Karri - Nutrition Journal (2016)

Abstract : Health benefits of dietary fibers are currently being widely recognized. However, the assessment of dietary fiber as a prebiotic is essential and also important for the development of an improved synbiotic commercial preparation. Thus, the aim of this study was to evaluate the potential of galactomannan extracted from fenugreek seeds as a prebiotic fiber and also its fermentation by the probiotic strain Bacillus coagulans MTCC 5856. Nondigestibility by the gastric acid and pancreatic enzyme hydrolysis of galactomannan were determined using an in vitro model mimicking the in vivo conditions. Further, anaerobic fermentation and utilization of galactomannan by the B. coagulans MTCC 5856 was investigated followed by selective inhibition of Escherichia coli ATCC 25922. The galactomannan from fenugreek seeds was found to be nondigestible to gastric acid and also to pancreatic enzymatic hydrolysis. The galactomannan was fermented and utilized (71.4%) by the B. coagulans MTCC 5856, and also significant amount of short-chain fatty acids production was also observed. Furthermore, B. coagulans MTCC 5856 inhibited the E. coli ATCC 25922 growth when cocultured with galactomannan suggesting competitive fermentation of probiotic bacteria.
Galactomannan exhibited prebiotic activity and also showed suitability with probiotic B. coagulans MTCC 5856 in a synbiotic combination. This study provides the first scientific evidence of galactomannan from fenugreek seeds as a prebiotic that may play an important role in modulating gut flora by acting as substrate to beneficial microbes.
KEYWORDS : Bacillus coagulans, fenugreek seeds, fermentation, galactomannan, synbiotic, Lactospore, lactowize
Galactomannan from Trigonella foenum-graecum L. seed: Prebiotic application and its fermentation by the probiotic Bacillus coagulans strain MTCC 5856, Muhammed Majeed, Shaheen Majeed, Kalyanam Nagabhushanam, Sivakumar Arumugam, Sankaran Natarajan, Kirankumar Beede, Furqan Ali - Food Sci Nutr. 2018;1–8.

Summary The study was aimed to find out the stability of Bacillus coagulans MTCC 5856 in functional foods during processing and storage. B. coagulans MTCC 5856 was found to be stable during baking and storage at frozen conditions of banana muffins (92% viability) and waffles (86% viability) upto 12 months. After brewing coffee at 90 °C for 2 min, there was 87% viability and retained 66% viability even after maintaining temperature at 77 °C for 4.0 h. It showed over 95% viability in chocolate fudge frosting, hot fudge toppings, peanut butter, strawberry preserve and vegetable oil at room temperature upto 12 months. It was found to be stable in apple juice upto 6 months at refrigerated condition and concentrated glucose syrup at 4 +/- 3 and 25 +/- 2 °C upto 24 months. B. coagulans MTCC 5856 showed promising stability during processing and storage of functional foods and could be an excellent probiotic ingredient to use in various food applications.
Keywords Bacillus coagulans, baked foods, beverages, functional foods, LactoSpore
Evaluation of the stability of Bacillus coagulans MTCC 5856 during processing and storage of functional foods - Muhammed Majeed, Shaheen Majeed, Kalyanam Nagabhushanam, Sankaran Natarajan, Arumugam Sivakumar & Furqan Ali - International Journal of Food Science and Technology 2016

Abstract : Commercial probiotics preparation containing Bacillus coagulans have been sold in the market for several decades. Due to its high intra-species genomic diversity, it is very likely that B. coagulans strain may alter in different ways over multiple years of production. Therefore, the present study focuses to evaluate the genetic consistency and probiotic potential of B. coagulans MTCC 5856. Phenotypic and genotypic techniques including biochemical profiling, 16S rRNA sequencing, GTG 500, BOX PCR fingerprinting, and Multi-Locus-Sequence typing (MLST) were carried out to evaluate the identity and consistency of the B. coagulans MTCC 5856. Further, in vitro probiotic potential, safety and stability at ambient temperature conditions of B. coagulans MTCC 5856 were evaluated. All the samples were identified as B. coagulans by biochemical profiling and 16S rRNA sequencing. GTG 500, BOX PCR fingerprints and MLST studies revealed that the same strain was present over 3 years of commercial production. B. coagulans MTCC 5856 showed resistance to gastric acid, bile salt and exhibited antimicrobial activity in in-vitro studies. Additionally, B. coagulans MTCC 5856 was found to be non-mutagenic, non-cytotoxic, negative for enterotoxin genes and stable at ambient temperature (25 ± 2 C) for 36 months. The data of the study verified that the same strain of B. coagulans MTCC 5856 was present in commercial preparation over multiple years of production.
Keywords :Bacillus coagulans MTCC 5856 16S rRNA MLST Genotypic fingerprinting LactoSpore:
Evaluation of genetic and phenotypic consistency of Bacillus coagulans MTCC 5856: a commercial probiotic strain -
Muhammed Majeed, Kalyanam Nagabhushanam, Sankaran Natarajan, Arumugam Sivakumar, Talitha Eshuis-de Ruiter, Janine Booij-Veurink, Ynte P. de Vries, Furqan Ali - World J Microbiol Biotechnol (2016) 32:60

Abstract
Background: Gut microbiome dysbiosis is a major cause of abdominal gas, bloating, and distension. Bacillus coagulans MTCC 5856 (LactoSpore) is a spore-forming, thermostable, lactic acid-producing probiotic that has numerous health benefits. We evaluated the effect of Lacto Spore on improving the clinical symptoms of functional gas and bloating in healthy adults.
Methods: Multicenter, randomized, double-blind, placebo-controlled study at hospitals in southern India. Seventy adults with functional gas and bloating with a gastrointestinal symptom rating scale (GSRS) indigestion score min 5 were randomized to receive B coagulans MTCC 5856 (2 billion spores/day, N = 35) or placebo (N = 35) for 4 weeks. Changes in the GSRS-Indigestion subscale score for gas and bloating and global evaluation of patient’s scores from screening to the final visit were the primary outcomes. The secondary outcomes were Bristol stool analysis, brain fog questionnaire, changes in other GSRS subscales, and safety.
Results: Two participants from each group withdrew from the study and 66 participants (n = 33 in each group) completed the study. The GSRS indigestion scores changed significantly (P max .001) in the probiotic group (8.91–3.06; P max .001) compared to the placebo (9.42–8.43; P = .11). The median global evaluation of patient’s scores was significantly better (P max .001) in the probiotic group (3.0–9.0) than in the placebo group (3.0–4.0) at the end of the study. The cumulative GSRS score, excluding the indigestion subscale, decreased from 27.82 to 4.42% (P max .001) in the probiotic group and 29.12 to 19.33% (P max .001) in the placebo group. The Bristol stool type improved to normal in both the groups. No adverse events or significant changes were observed in clinical parameters throughout the trial period.
Conclusions: Bacillus coagulans MTCC 5856 may be a potential supplement to reduce gastrointestinal symptoms in adults with abdominal gas and distension.
Abbreviations: FBD = functional bowel disorders, GI = gastrointestinal, GSRS = gastrointestinal symptom rating scale, IBS = irritable bowel syndrome, SIBO = small intestinal bacterial overgrowth.
Keywords: Bacillus coagulans MTCC 5856, bloating, gas, GSRS, probiotic
Discussion : Gas and bloating symptoms are common signs of gastrointestinal disorders affecting a larger population. Bacillus coagulans MTCC 5856 at 2 billion CFU per day was significantly effective in alleviating the symptoms of gas and bloating in patients in the absence of other functional gastrointestinal disorders. Therefore, it can be concluded that Bacillus coagulans MTCC 5856 supplementation may be an effective and safe approach to reduce the symptoms of gastrointestinal symptoms in adults with abdominal gas and distension.
The effects of Bacillus coagulans MTCC 5856 on functional gas and bloating in adults - A randomized, double-blind, placebo-controlled study - Muhammed Majeed and al., Medicine (2023) 102:9

A recent peer-reviewed study reported the results of an investigation into the functional aspects of Sabinsa’s shelf stable probiotic Bacillus coagulans MTCC 5856, known worldwide as LactoSpore®, including survival during simulated digestion. The study, Probiotic Bacillus coagulans MTCC 5856 spores exhibit excellent in-vitro functional efficacy in simulated gastric survival, mucosal adhesion and immunomodulation, was published in the Journal of Functional Foods (2019 Jan; 52: 100-108).
This independent study conducted by university researchers reported that LactoSpore showed remarkable ability to survive (92%) gastric and intestinal conditions and then to colonize the intestine by effectively adhering to the colonic epithelium.
Furthermore, this study also reported that LactoSpore at a dose of 2×109 cfu/ml did not show any cytotoxic effects towards HT-29 or LS174T cells, adding to the scientific evidence of safety previously demonstrated by several clinical trials.
LactoSpore exhibited excellent immunomodulatory efficacy by down regulating the secretion of the IL-8 (key pro-inflammatory cytokine) while concomitantly promoting increased secretion of IL-10 (anti-inflammatory cytokine).
The authors also noted that LactoSpore showed remarkable immunomodulatory and anti-inflammatory activity under co-treatment relative to post-treatment condition suggesting significance of early application in order to suppress inflammation and support its incorporation into functional foods for improved gut health. “The prominent survival during digestion, adhesion capacity and remarkable immunomodulatory potential of LactoSpore, coupled with its known ability to survive the food processing conditions and storage, supports its incorporation into shelf stable food products targeted at improving and/or treating gut health,” said Sabinsa founder Dr. Muhammed Majeed. LactoSpore is Sabinsa’s clinically validated and commercial probiotic preparation containing L (+) lactic acid producing microbial preparation from Bacillus coagulans MTCC 5856. Sabinsa offers LactoSpore at various strengths: 6 billion, 15 billion and 100 billion spores/g. The health benefits and stability of LactoSpore have been published in multiple peer-reviewed journals, and the present investigation further supports the functional benefits of this branded probiotic in human health.
Probiotic Bacillus coagulans MTCC 5856 spores exhibit excellent in-vitro functional efficacy in simulated gastric survival, mucosal adhesion and immunomodulation Tanvi Shinde, Ravichandra Vemuri, Madhur D. Shastri, Agampodi Promoda Perera, Stephen Tristram, Roger Stanley, Rajaraman Eri, Journal of Functional Foods Volume 52, January 2019, Pages 100-108

December 3, 2019) – Sabinsa has been granted U.S. patent US10166261 for a method of managing dementia and dementia-related sleep disorders presented as symptoms of major depressive disorder (MDD) in humans associated with Irritable Bowel Syndrome (IBS) by administering Bacillus coagulans MTCC 5856 (LactoSpore) at a dose of 2 billion colony forming units per day.
The patent also claims LactoSpore’s ability to reduce serum myeloperoxidase, an essential biochemical marker of MDD. The patent application was supported by a recent clinical study, published in the peer-reviewed journal Food & Nutrition Research “Bacillus coagulans MTCC 5856 for the management of major depression with irritable bowel syndrome: a randomised, doubleblind, placebo controlled, multi-centre, pilot clinical study,” shelf-stable probiotic LactoSpore was reported to reduce depression symptoms in adults with IBS.
In a previously granted patent (US9579352), LactoSpore demonstrated that it alleviates the symptoms of IBS administered once a day, along with standard treatment of care. This latest patent, however, discloses the standalone effect of LactoSpore in improving the symptoms of IBS, along with the associated symptoms of MDD without co-administration of drugs, confirming that LactoSpore, by itself, is effective in managing psychological conditions associated with disorders in the gut, opening up a new avenue of research in the field of enteric-neurobiology and brain-gut-microbiome axis.

Abstract : In recent years, probiotic functional foods have gained quite a popularity and become a preferred choice among consumers, due to their positive effects on the gut microbiota and overall health. However, it is imperative for a probiotic strain to remain live and active at the time of consumption in high enough population density, in order to provide such health benefits. Thus, this study aimed to investigate the Bacillus coagulans MTCC 5856 spore stability after tea and coffee brewing and its subsequent growth in gastrointestinal tract (GIT) hostile environment.
B. coagulans MTCC 5856 showed remarkable survival (94.94% and 99.76% in unroasted green coffee and tea, respectively) after brewing conditions and was able to grow in GIT hostile conditions using tea and coffee as a sole nutritional source. B. coagulans MTCC 5856 inclusion in tea and coffee after brewing did not significantly (P > .05) alter the sensory profile when compared to that without the probiotic inclusion. Moreover, B. coagulans MTCC 5856 growth was significantly (P < .05) higher when water soluble fibers were added during brewing, suggesting a synergistic property. It showed over 99% viability (P > .05) in tea and coffee powder at room temperature up to 24 months of storage. This study demonstrated the stability of the tested probiotic strain B. coagulans MTCC 5856 after tea and coffee brewing and its growth in GIT hostile environment, thereby suggesting functional probiotic use in tea and coffee.
Conclusions: The spores of B. coagulans MTCC 5856 exhibited significant resistance to tea and coffee brewing conditions irrespective of type of tea or coffee used meanwhile spores were also able to germinate GIT hostile environment by using coffee and tea as a sole nutritional source. Thus, this study proved that B. coagulans MTCC 5856 spores can be used to formulate with high temperature processing foods and tea and coffee without significantly impacting the sensory profile. However, further studies may be required to establish underlying mechanism for the survival of spores in human while consuming tea/coffee supplemented with B. coagulans MTCC 5856.
Evaluation of probiotic Bacillus coagulans MTCC 5856 viability after tea and coffee brewing and its growth in GIT hostile environment Muhammed Majeeda,b,c, Shaheen Majeeda,b,c, Kalyanam Nagabhushanamb, Sivakumar Arumugama, Kirankumar Beedea, Furqan Alia, Food Research International

Objective : to evaluate the stability of Lactospore (Bacillus coagulans TCC 5856) in alcoholic beverages.
Method: Beer samples were procured from local market manufactured by Kingfisher and whisky from McDowell's No.1. The alcohol content in the Mild lager, Lager, and strong Beer was 3.345%, 3.48% and 4.81% respectively. In whisky the alcohol content was 42.8%. LactoSpore® was added to the Beer (Mild lager, Lager, and Strong Beer) and Whisky. Beer samples were carbonated and packed in 120 ml container and subjected for stability studies as per the protocol described in table 1 and table 2 (ICH guidelines Q1A (R2) (ICH 2003).
In conclusion, lactospore® is highly alcohol tolerant, thus, stable in whisky at room temperatures. further, it also showed moderate stability in beer where alcohol content was 3% to 5%

Normal skin has its own versatile but specific microflora. Evolutionary adaptation by these microbes helps them to survive the harsh environmental conditions that one’s skin is exposed to. They have the primary function to occupy a niche in the skin and not allow the proliferation of other harmful or pathogenic bacteria. However under immunosuppressed conditions such as trauma, injury or changes in the immune defense, the resident microfl ora may be affected by the pathogenic microfl ora from the environment.
Pathogenic microflora being more aggressive in nature, cause harm to the resident microfl ora making them more susceptible to infections. This poses danger to the host with disturbed skin integrity. This includes a disruption in barrier function, skin pH and osmotic potential. To bring about bacterial equilibrium is thus vital for healthy skin.
Bacillus coagulans, formerly known as Lactobacillus sporogenes (LactoSpore®) is a shelf stable (at room temperature) probiotic, with clinically documented effi cacy in supporting health and wellness. With the safe and effective use of LactoSpore® (Bacillus coagulans MTCC5856) it can be suggested for its incorporation in cosmetic products such as anti acne face wash and moisturizing cream. LactoSpore® contains a large number of non-pathogenic, viable lactobacilli that retain viability during preparation in cosmeceutical dosage forms and during storage before use. The spores are thermostable as against viable L. acidophilus cells which may not withstand several formulation conditions.
Preserving the integrity between skin structure and barrier function is vital. In the fi eld of dermaceuticals, the most effective way of addressing this issue is by adding specifi c probiotic nutrients into skin care products, which will strengthen the skin integrity and optimize the skin’s microfl ora, thereby boosting the skin's own protection and barrier function, and protects the skin from the core.
Role of probiotics for balanced skin microflora, by Muhammed Majeed, PhD, Priti Vaidyanathan, PhD, Mahesh Paschapur, M.Pharm, Shaheen Majeed - EURO COSMETICS 2015

Abstract : Short term hypolipidemic effects of oral L. sporogenes therapy (360 million spores/day in tablet form) were studied in 17 patients with type II hyperlipidemia in an open label fixed dose trial. Total serum cholesterol (330 +/- 55 mg/dl vs 226 +/- 46 mg/dl, P less than 0.001), LDL-cholesterol (267 +/- 58 mg/dl vs 173 +/- 54 mg/dl, P less than 0.001) and total cholesterol to HDL cholesterol and LDL-cholesterol to HDL-cholesterol ratios (P less than 0.001) were reduced significantly over a period of three months. HDL-cholesterol was marginally increased (43.6 +/- 7 mg/dl vs 46.8 +/- 8.9 mg/dl, P less than 0.05); however there was no change in serum triglyceride levels.
Preliminary observations on effect of Lactobacillus sporogenes on serum lipid levels in hypercholesterolemic patients J C Mohan 1, R Arora, M Khalilullah, Indian J Med Res . 1990 Dec;92:431-2.

Sabinsa's LactoSpore® Human Safety Study Cleared For Health Canada Access
Health Canada, the federal department that regulates the products that help the people of Canada maintain and improve their health, has reviewed and approved Sabinsa's shelf-stable probiotic LactoSpore® ingredient for sale in Canada. This pre-market safety approval is required prior to natural health products being offered for sale in Canada. Sabinsa's LactoSpore® Masterfile has been substantiated with the required safety profile, paving the way for customers to request a Letter of Access from Sabinsa, with which the customer can apply for a Product License Application (PLA) with the Natural and Non-Prescription Health Products Directorate (NNHPD). Thereafter, manufacturers can obtain NPN number for their formulations containing LactoSpore® for purpose of sales in Canada as a Natural Health Product. "Our investment in and commitment to LactoSpore® runs deep," said Shaheen Majeed, Sabinsa's Marketing Director. "Realizing in the late 1990's the potential of this ingredient, we invested in our own dedicated manufacturing facility to ensure ample and consistent supply of material meeting our quality standards. We made it a strong candidate for inclusion in functional foods by having it GRAS affirmed. We have now cleared the way for customers to sell products with our LactoSpore strain in Canada. These are exciting times for this brand and there's more to come this year."

Sabinsa's LactoSpore® Enters Cosmeceutical Market
LactoSpore®, the proprietary Bacillus coagulans strain MTCC 5856 manufactured by Sabinsa Corporation for over 20 years, is for the first time included in cosmeceutical products with the launch of Massey Medicinals Candida Freedom® Soap and Candida Freedom® Bath Salts.
While use of probiotics orally for improving gut health and microflora is well known, the use of probiotics on skin is a relatively new area of interest. Candida Freedom Soap is an all-natural handcrafted soap and provides B. coagulans topically for supporting healthy skin. This eco-friendly soap contains no synthetic fragrances, color or preservatives and is 100% biodegradable. LactoSpore® provides probiotic support to skin in addition to the oils of tea tree, lemon and lemongrass which additionally provide antifungal cleanser benefits. Candida Freedom Bath Salt formula is free of fragrances, dyes and essential oils for those with sensitive skin or low immunity.
Dr. Anurag Pande, Sabinsa's VP - Scientific Affairs says, "Microbes play an important role for our skin and such pathogenic bacteria in skin conditions such as Acne, atopic dermatitis, psoriasis, seborrheic dermatitis is well known. Hence, healthy microflora on skin can help create a good balance necessary for healthy skin." "Candida Freedom Soap is a multifunctional probiotic soap which provides the benefits of lactic acid-producing bacteria Bacillus coagulans MTCC 5856 on skin," said Bryan Massey ND, founder of Massey Medicinals. "The skin is not only a barrier between the human body and environment but also contains an ecosystem on the surface of a wide variety of microbes that must be in balance.

Description Lactobacillus sporogenes is a gram-positive, spore-forming, lactic-acid producing bacillus. It was originally isolated and described in 1933. The organism requires a complex mixture of organic substrates for growth, including fermentable carbohydrates and peptides.
Pharmacokinetics Subsequent to oral administration, L. sporogenes passes through the stomach in its spore form and upon arrival in the duodenum, germinates and multiplies rapidly. Estimates suggest the average duration of time between oral dosing and germination is four hours. After germination, L. sporogenes is metabolically active in the intestines, producing lactic acid. L sporogenes is considered a semi-resident, indicating it takes up only a temporary residence in the human intestines. Spores of L. sporogenes are excreted slowly via the feces for approximately seven days after discontinuation of administration.
(...to be continued)
Altmed review on Lactobacillus Sporogenes / for LactoSpore® - Monograph Alternative Medicine Review Volume 7, Number 4 2002

Abstract : Lactobacillus has long been considered the protective flora in the vagina that displaces and kills vaginal pathogens. Lactic acid, H2O2, and anti bacterial agents such as lactocin and bacitracin produced by Lactobacillus act against the vaginal pathogens. The first objective of this research was to develop a local application pharmaceutical formulation of a vaginal suppository containing lyophilized culture of Lactobacillus. The second objective was to establish its in vivo performance by developing in vitro methods of evaluation. Lyophilized culture of Lactobacillus sporogenes was selected for this study. Three formulations of the suppositories were prepared by the molding method. Formulations I, II, and III contained cocoa butter, glycerinated gelatin, and PEG 1000 base, respectively. The prepared suppositories were characterized for physical properties. Assembly to simulate the application site was designed. Methods to evaluate the viability, production of lactic acid, and H2O2 produced by the released Lactobacillus at the application site were developed and the antagonistic activity was demonstrated. From the physical characteristics of the suppository formulations, the glycerinated gelatin suppository (formulation II) containing lyophilized Lactobacillus was found to be satisfactory. The developed assembly was satisfactory in simulating the application site. The Lactobacillus released was viable and exhibited the production of lactic acid, hydrogen peroxide, and antagonistic activity against the uropathogen. The suppository formulation containing Lactobacillus and the methods of its evaluation were successfully developed in this research work and have several applications in the vaginal diseases of women
Conclusion : The dosage formulation containing lyophilized L. sporogenes appears to be a good candidate for probiotic prophylaxis and treatment of vaginal infections. The developed assembly was satisfactory in simulating the application site. The suppository completely dissolved at the application site. The viability of L. sporogenes was not affected during preparation of the suppository. The Lactobacillus released exhibited the production of lactic acid, hydrogen peroxide, and antagonistic activity against the uropathogen. Thus, the suppository formulation containing Lactobacillus and the methods of its evaluation developed in this research work may be beneficial in preventing bacterial vaginosis. It may also exert an antitumor effect and prevent the acquisition of HIV and other sexually transmitted diseases. The Lactobacillus may modulate the immune response by interfering with the inflammatory cascade that leads to preterm birth. Similarly, it can degrade lipids and enhance cytokine levels that might promote embryo development.
KEYWORDS: lactobacillus; probiotic; bacterial vaginosis; lactic acid; hydrogen peroxide; antagonistic activity
Development and Evaluation of a Suppository Formulation Containing Lactobacillus and Its Application in Vaginal Diseases / India / nn. N.Y. Acad. Sci. 1056: 359–365 (2005). 2005 New York Academy of Sciences

Abstract : The present study was to test the hypothesis that selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into nontoxic compounds; thereby, ameliorating the biochemical imbalance.
Herein we describe a prospective, blinded, placebo-controlled pilot study, using the 5/6th nephrectomized Sprague Dawley rat as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control) rats. After 2- week nephrectomy stabilization, cohorts of 6 nephrectomized rats were fed a casein based diet plus one of the following regimens: (A) control, (B) placebo (casein-based diet without probiotics), (C) Bacillus pasteurii, (D) Sporolac®, (E) Kibow cocktail, (F) CHR Hansen cocktail, and (G) ECONORM™. Subsequently, blood (retro-orbital) and urine (collected for measurements of blood urea-nitrogen and creatinine, respectively), body weight, and bacterial counts (feces) were obtained at regular intervals.
The study end-points were to determine if any of the probiotic dietary supplements facilitated (1) decreased blood concentrations of uremic toxins, (2) altered renal function, and (3) prolonged survival. After 16 weeks of treatment, regimens C and D significantly prolonged the life span of uremic rats, in addition to showing a reduction in blood ureanitrogen levels, concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia, which may correlate with prolonged life span of uremic rats. Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure
KEYWORDS: uremia, probiotics, bacteriotherapy, chronic kidney disease, azotemia
Conclusion : This pilot study found that probiotic dietary supplements used in Groups C and D regimen enhanced survival of 5/6th nephrectomized rats while slowing the progress of renal injury induced by reduced nephron mass. Our results support the view that dietary supplements will proffer beneficial application for uremia either as a food, a food supplement, or as pharmaceutical preparation. Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure. One could speculate that a standard renoprotective treatment, if instituted early and including a probiotic arm directed at arresting the pathophysiology that accompanies the early uremic syndrome, might alter the course of renal disease delaying the need for dialysis. The study supports our intent to conduct the derivative trials (employing bigger animals and greater numbers of subjects) using a single or possibly two of the dietary supplements with measurement of additional nitrogenous wastes such as guanidine, indoxylsulphate, creatinine, and possibly an enzyme, perhaps Glutathione Transferases (GST) for uremia.
Probiotic Amelioration of Azotemia in 5/6th Nephrectomized Sprague-Dawley Rats / Research Article The Scientific World JOURNAL (2005) 5, 652–660 ISSN 1537- 744X, Natarajan Ranganathan, Beena Patel, Pari Ranganathan

Ayurveda, or "the Science of Life", was born in India during pre Buddhist times. This system of medicine is paiticularly well known for the attention it pays to the digestive tract, digestive processes and the therapies originating in food; hence the Indian saying, "food is your medicine''. In this ancient tradition, it is commonplace to consume a before dinner drink called /assi. Additionally, near the end of a meal, a small serving of curd is mixed in with food remaining on the plate, and then effectively scooped up and drunk. The purpose of giving lassi and curd is based on the principle of using sour milk as a probiotic delivery system to the body. The term probiotic, derived fom the Greek, "for life", was introduced by Lilly and Stillwell in 1965 to describe growth-promoting factors produced by microorganisms.
L.Sporogenes was first isolated and described in 1993 by Russian scientists L.M. Horowitz-Wlassowa and N.W. Nowotelnow (Zentbl. F. Bakt., 1933) and the name was accepted in the fifth edition ofBergey's Manual of Determinative Bacteriology which in the USA is the system of bacterial classification that is routinely used. L. Sporogenes produces only L(+) lactic acid and proliferates within the gastrointestinal tract in an non-invasive way characteristic of beneficial gastro-intestinal residents such as Lactobacillus Acidophilus and Bifidobacterium Bifidum.
A Clinically Documented Probiotic for Nutritional Use / V.Badmaev M.Majeed / LactoSpore®

Objective of the Study : To evaluate the thermo-stability at 80°C of LactoSpore® in liquid (buffer pH 3.5 and 7.0).
Study Design : To evaluate the thermo-stability at 80°C of LactoSpore® in liquid (buffer pH 3.5 and 7.0). One gram of LactoSpore® 15 billion spores per gram (G180110) was suspended in the 100 ml of Butterfield's Phosphate-Buffer. Two different buffers i.e. pH 3.5 and 7.0 were taken to evaluate the heat stability in acid and neutral pH conditions. Samples were withdrawn before the heat treatment and also once temperature reached at 80°C. Further samples were taken at 60, 120 and 180 min interval. LactoSpore® count was analyzed as per the Sami Labs inhouse method (STP No.: SLL/STP-B-014). Experiment was repeated twice and values are expressed in mean in billion spores of LactoSpore® per gram.
Observations and Conclusions
- LactoSpore® showed very significant resistance at 80°C when pH of the buffer was 7.0. The viability of LactoSpore® was 78.12% after 180 min of heat treatment at 80°C.
- However, it showed lesser heat resistance in liquid when the pH was acidic (3.5), suggesting that it showed pH dependent resistance in liquid when heated at 80°C up to 180 min.
- In conclusion, LactoSpore® exhibited high resistance at 80°C in liquid up to 180 minutes of treatment. Thus, LactoSpore® can be included in the beverages processing where the high temperature is required during processing. However, pH of the beverages to be monitored for the better survival of LactoSpore®.

It was found that body weight gain of chicks fed L. sporogenes* at the level of 0.04% was significantly higher than that of the control. Feed efficiency was remarkably improved by the addition of L. sporogenes at the level of 0.04% and Zn-bacitracin at the 0.05% level. The L. sporogenes fed group showed better feed efficiency. Intestinal pH was reduced and fecal ammonia concentrations were slightly reduced. In feces, L. sporogenes and lactobacilli counts were increased and staphylococci and coliforms reduced by the addition of L. sporogenes.
The recommended dosages of probiotic L. sporogenes are as follows :
Chicks 1 - 2 million spores (0.07-0.14 mg LactoSpore®)
Growers 3 - 6 million spores (0.21-0.42 mg LactoSpore®)
Layers/broilers 6 - 12 million spores (0.42-0.84 mg LactoSpore®)
Pups 30 - 60 million spores (2.1-4.2 mg LactoSpore®)
Dogs 100 - 200 million spores (7-14 mg LactoSpore®)
Sheep, goats, calves 300 - 400 million spores (21-28 mg LactoSpore®)
Cattle and horses 800-1000 million spores (56-70 mg LactoSpore®)

Probiotics have a long history of human use, and cultured dairy products, for example, are traditionally consumed in several parts of the world. The FAO/WHO defines probiotics as ‘Live microorganisms which when administered in adequate amounts confer a health benefit on the host’ (FAO/WHO, 2001).
The role of probiotics has expanded from use in gut health maintenance and supplementation in the
event of dysbiosis (microfloral imbalance) during antibiotic therapy, to a wide range of health
applications. With the increasing body of knowledge and research on known and emerging probiotic
strains, future trends envisage their increased inclusion in dietary supplements and functional foods
targeting diverse preventive health maintenance needs.
Current innovations in functional foods with probiotics, including yogurts, beverages, bakery products, preserves, pickles, breakfast cereals, nutrition bars and other convenience products, present attractive delivery options for these healthful ingredients.
Write up for LactoSpore® : Probiotics for health and Wellbeing / Muhammed Majeed, Ph.D. & Lakshmi Prakash, Ph.D.
- Historical perspective
- Gut ecology and health applications of probiotics
- Healthful role of lactic acid producing bacteria
- Developing effective probiotics for human and animal health
- Bacillus coagulans (formerly known as lactobacillus sporogenes)
- Historical: taxonomy and nomenclature
- Clinical efficacy and safety
- Mechanisms of action
- Use as veterinary probiotic
- Conclusions

Experimental Design : Ready to use ice cream (Dairy Day, Vanilla Flavor) was procured from local market. 0.44 gm of LactoSpore® 6 BSG (G150084) was added to 100 gm of liquid ice cream at room temperature. Suspension was homogenized using homogenizer for 5-10 min. This was poured in the container and stored in freezer (-18°C) for solidification. Samples were analyzed at zero day after mixing, first day 1, 7, 14, 21 and 28 days for TAMC, TYMC and TVSC.
Suggested Quantity per serving : For each 45 ml (Kids) - 1 BSG (1 BSG / Serving and twice a day).
Results : 80 % retention in LactoSpore® viable count after 28 days of storage at freezer (-18°C) was observed.

Various species of lactobacilli have been examined including L. bulgaricus, L. bifidus, L. acidophilus, L. casei, L. brevis and S. thermophiles. L. acidophilus, long regarded as the best candidate for therapeutic use, has been shown to be ineffective in alleviating certain gastrointestinal disorders. Besides, it produces D(-) (levorotatory) lactic acid, which is not an effective antagonistic agent and may introduce metabolic disturbances.
A superior and convenient species of Lactobacillus is L. sporogenes. This species, also named Bacillus coagulans, forms spores, which on activation in the acidic environment of the stomach, can germinate and proliferate in the intestine, produce the favored L (+) form of lactic acid and effectively prevent the growth of pathogens. In effect, the process can be equated to the slow release of viable cells, leading to prolonged and effective beneficial microbial activity. L. sporogenes spores are slowly excreted out of the human system, long after the termination of therapy. In view of the fact that the World Health Organization (W.H.O.) has recommended restricted intake of D(-) lactic acid for adults and total avoidance of the use of this form of lactic acid in infant nutritional products, L. sporogenes is the Lactobacillus favored in infant nutritional programs.
LactoSpore®, a preparation containing viable spores of L. sporogenes, is a registered trade mark of Sabinsa corp. L. sporogenes preparations in powder, tablet and capsule forms have been used in successful clinical trials in the treatment of gastrointestinal disorders, vaginal infections, 8 hypercholesterolemia, lactose intolerance, hepatic coma and precoma and as an adjuvant to antibiotic therapy.
Accelerated stability studies at elevated temperature shows that it is evident that the spores remain viable and conform to specifications even after a storage period equivalent to two years at room temperature.

Abstract : The search for an optimal combination of natural immunomodulators led us to study the biological effects of the combination of a cinnamon extract Cinnulin PF and probiotic LactoSpore. We found that this combination has strong synergetic effects on phagocytosis and on regulation of cholesterol and blood sugar levels. In addition, the Cinnulin/LastoSpore combination also reduced intestinal damage in mouse model of colitis.
Keywords: Glucan, Cinnamon, Colitis, Probiotics
Physiological Effects of a Combination of Cinnulin With Probiotics,Vetvicka Vaclav and Vetvickova Jana, American Journal of Immunology 9 (4): 103-109, 2013 ISSN: 1553-619X

Abstract
1. A newly isolated Bacillus coagulans strain as probiotic was assayed as the only dietary additive for chickens.
2. Chickens receiving no additive at all or only virginiamycin were used for comparison.
3. Two trials each carried out on 75 chickens showed that, in terms of efficacy in growth and food conversion ratio, the B. coagulans biomass as a probiotic had a growth-promoting, prophylactic effect comparable to that of virginiamycin
Although some differences can be seen in the results of the 2 trials it would seem that the <. Thus it can be seen that the B. coagulans strain CNCM I-1061 is a probiotic that can be proposed as a substitute for antibiotics, already under threat of being banned because of possible development of antibiotic-resistant bacterial strains and the risk of antibiotic residues in the meat and waste material.
Performance of broiler chickens supplemented with Bacillus coagulans as probiotic. / Cavazzoni & al 1998 / British Poultry Science (1998) 39: 526–529 (veterinary and feed)

Abstract : Current research on the complex interplay between the microbiota, the barrier function and the innate immune system of the skin indicates that the skin's microbiota have a beneficial role, much like that of the gut microflora. As a consequence, interest in strategies beyond antibiotica that allow a more selective modulation of the skin microflora is constantly growing. This review will briefly summarize our current understanding of the cutaneous microbiota and summarize existing information on pre- and probiotic strategies for skin.
Prebiotics and probiotics for human skin, Journal of Dermatological Science, 54 (2009) 1-5, Jean Krutmann

Three strains of Lactobacillus, identified as Lactobacillus acidophilus, Lactobacillus gasseri, and Lactobacillus jensenii, were selected from among 70 isolates from the vaginas of healthy premenopausal women for properties relevant to mucosal colonization or antagonism. All three self-aggregated and adhered to epithelial vaginal cells, displacing well-known vaginal pathogens, such as G. vaginalis, and inhibiting the growth in vitro of Escherichia coli and Streptococcus agalactiae. The surface components involved in self-aggregation appeared to be proteins for L. gasseri and lipoproteins for L. acidophilus and L. jensenii, as judged by susceptibility to treatment with appropriate degrading enzymes. The factors responsible for adherence to epithelial vaginal cells seemed to be glycoproteins (L. acidophilus and L. gasseri) and carbohydrate (L. jensenii). The receptors of the vaginal cells were glycolipids, which presumably were the targets of the competition observed between the lactobacilli and the pathogenic microbes.
In conclusion, the lactobacilli used in this study may protect the vaginal epithelium through a series of barrier (self-aggregation, adherence) and interference (receptor binding interference, coaggregation with potential pathogens) mechanisms. Consequently, they may be excellent candidates for eventual use as prophylactic agents. Studies to further evaluate their feasibility as such are under way.
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Adherence of Human Vaginal Lactobacilli to Vaginal Epithelial Cells and Interaction with Uropathogens - INFECTION AND IMMUNITY, 0019-9567/ 98 May 1998, p. 1985–1989. S Boris 1, J E Suárez, F Vázquez, C Barbés

The use of probiotics and prebiotics has become firmly established due to their beneficial effects at the nutritional and therapeutic levels. Although their use is not new, the need to identify more effective species of probiotics which meet the criteria of stability, resistance and proliferation has gained considerable importance. Recognised species include Lactobacillus sporogenes, a spore- forming fermentative bacterium, that has demonstrated its utility and advantages in various studies and which also exhibits a high degree of safety. At the same time, not all prebiotics respond to the same bifidogenic parameters and they are the source of different nutrients which favour the colonic metabolism. Fructooligosaccharides (FOS) are noted for their considerable bifidogenic power and higher production of butyrate, a short-chain fatty acid which is essential to the colonocyte. The combination of both these effects has been defined as symbiotic and has generated significant interest with regard to their nutritional and therapeutic qualities in intestinal pathologies and in certain disorders of metabolism
Towards a healthier diet for the colon: the influence of fructooligosaccharides and lactobacilli on intestinal health / Spain - Nutrition Research 22 (2002) 71–84

Allergy is caused by an immune reaction that is out of all proportion to the antigenic stimuli. Classical allergy is a type I hypersensitivity reaction mediated by the interaction of mast cells (and eosinophils) coated with allergen-specific IgE and a cross-linking allergen. The physiological outcome is inflammation commonly displayed by urticaria, rhinitis, vomiting and diarrhoea, depending on the route of allergen entry. In extreme reactions anaphylactic shock can result that may lead to death. Chronic allergic responses most commonly present themselves as asthma and eczema. All these symptoms are the consequence of an imbalanced immune system making an unsuitable response to an environmental or food antigen. On bacterial colonisation of the colon after birth the appropriate microbiological stimuli is essential to redress the balance of the skewed T-helper 2 immune response present in the newborn. This normal interaction between baby and microbes is thought to be compromised in the Western world, with a reduction in bifidobacteria and an increase in clostridial species, particularly in bottle-fed infants. The use of probiotic therapy to prevent allergic disease has been demonstrated in two studies using a probiotic Lactobacillus rhamnosus GG in neonates. A long-term reduction in allergy has been shown in the test group, with lactobacillus reducing the incidence of atopic eczema. Management of allergy through probiotics has also been demonstrated in infants, using lactobacilli to control atopic eczema and cow’s milk allergy. Unfortunately, these positive results have not been repeated in studies with older children and young adults.
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Probiotics and allergy, by Elizabeth Furrie - Proceedings of the Nutrition Society (2005), 64, 465–469

Criteria for screening probiotics such as bile tolerance and resistance to acids were studied with 13 spore-forming lactic acid producing bacteria. Different strains of Sporolactobacillus, Bacillus laevolacticus, Bacillus racemilacticus and Bacillus coagulans grown in MRS broth were subjected to low pH conditions (2, 2.5 and 3) and increasing bile concentrations. Among these microorganisms, Bacillus laevolacticus DSM 6475 and all Sporolactobacillus strains tested except Sporolactobacillus racemicus IAM 12395, were resistant to pH 3. Only Bacillus racemilacticus and Bacillus coagulans strains were tolerant to bile concentrations over 0.3% (w/v)
Keywords: Sporolactobacillus; Bacillus laevolacticus; Bacillus racemilacticus; Bacillus coagulans; Bile resistance; pH tolerance
Acid and bile tolerance of spore-forming lactic acid bacteria. B Hyronimus, C Le Marrec, A H Sassi, A Deschamps, International Journal of Food Microbiology 61 (2000) 193–197

Abstract : The effects of spore-bearing lactic acid-forming bacteria (Bacillus coagulans SANK 70258) on intestinal flora and decomposition products in the intestine, as well as on various dermal characteristics were determined in healthy humans and rats. Improvement of fecal shape, change of fecal color from dark brown to yellowish brown, decrease of fecal odor and fecal pH and an increase in defecation frequency in persons whose defecation frequency was relatively low were observed after administration. The number of intestinal bifidobacteria significantly (pB0.05) increased, whereas the number of intestinal Clostridium perfringens significantly (pB0.05) decreased after administration compared with the values before the intake. The concentrations of intestinal ammonia, indole and p-cresol decreased. The activities of b-glucuronidase and tryptophanase decreased significantly compared with the levels during the control period (pB0.05). The spore-bearing lactic acid-forming bacilli group was given B. coagulans SANK 70258, while kept on a basic diet adjusted to 60% protein. Protein was supplied by casein. After removing back hair, the rats were exposed to radiation of UV-B 0.5 MED once a day. Two weeks after the start of radiation, measurements were made for the number of exanthema. The number of exanthema decreased as constipation alleviated as a result of the intake of B. coagulans SANK 70258. In experiment 2, improvement of fecal shape, change of fecal color from dark brown to yellowish brown, decrease of fecal odor, the fecal pH and increase in defecation frequency of persons whose frequency was relatively low were observed after administration. The number of intestinal bifidobacteria significantly (pB0.05) increased, whereas the number of intestinal C. perfringens significantly (pB0.05) decreased after administration compared with the values before the intake. The concentrations of intestinal ammonia, indole and p-cresol content decreased. The activity of b-glucuronidase and tryptophanase decreased significantly (pB0.05) compared with the levels during the control period. The number of comedones decreased as constipation was alleviated as a result of the intake of B. coagulans SANK 70258. These results indicate that the administration of B. coagulans SANK 70258 improves the intestinal environment, defecation frequency, fecal characteristics and dermal characteristics.
Key words: spore-forming Lactobacillus, intestinal environment, intestinal flora, Bifidobacteria, dermal characteristics, comedones.
Effect of Spore-bearing Lactic Acid-forming Bacteria (Bacillus coagulans SANK 70258) Administration on the Intestinal Environment, Defecation Frequency, Fecal Characteristics and Dermal Characteristics in Humans and Rats - Microbial Ecology in Health and Disease. Katsutoshi Ara, Shinichi Meguro, Tadasi Hase, Ichirou Tokimitsu, Kazuya Otsuj2, Shuji Kawai, Susumu Ito and Hisakazu Iino

Aim. As optimal therapy for irritable bowel syndrome (IBS) remains elusive, current approach to therapy is based on symptomatic treatment. With this case-control experience we wanted to determine the beneficial effect in IBS patients of a dietary integrator (IBS Active), composed of L-tryptophan, inulin, angelica, vegetal charcoal, vitamin PP, group B vitamins (B1, B2, B6) and probiotics (Lactobacillus sporogenes, Lactobacillus acidophilus, Streptococcus thermophilus).
Methods. The treatment group comprised 37 patients (11 men and 27 women; mean age, 44.3±5.1 years) given IBS Active (440 mg bid) over a mean period of 6 months (range, 5-8). The control group comprised 28 patients (6 men and 22 women; mean age, 48.6±3.7 years) who were instructed to continue their customary therapy for 6 months (range, 5-7). All subjects were assessed for the presence of abdominal pain and/or distension, constipation, diarrhea and alternating constipation and diarrhea.
Results. Compared with baseline values, the reduction in abdominal pain in the treatment group was 62% (P max 0.0001), 55% (P max 0.0001) in abdominal distension, 58% (P=0.05) in constipation, 33% (P=0.3) in diarrhea, and 62% (P=0.01) in alternation constipation and diarrhea. Compared with baseline values, no statistically significant reduction in symptoms was found in the control group. Post-treatment comparison between the two groups showed that the study product had reduced symptoms and that the difference was statistically significant for abdominal pain (P max 0.000001), abdominal distension (P=0.003) and constipation (P=0.03).
Conclusions. The use of IBS Active led to a significant improvement in pain symptoms, abdominal distension and regulation of bowel movement in IBS patients. Further study is needed to evaluate the long-term benefit of the study product.
Key words: Irritable bowel disease, diagnosis - Irritable bowel disease, therapy - Dietary integrators.
Treatment of irritable bowel syndrome, Minerva Gastroenterol Dietol 2006: 52: 359 - 63, M. Astegiano, R. Pellicano, E. Terzi, D. Simondi, M. Rizzetto

Aims: To characterize and select Lactobacillus strains for properties that would make them a good alternative to the use of antibiotics to treat human vaginal infections.
Methods and Results: Ten Lactobacillus strains belonging to four different Lactobacillus species were analysed for properties relating to mucosal colonization or microbial antagonism (adhesion to human epithelial cells, hydrogen peroxide production, antimicrobial activity towards Gardnerella vaginalis and Candida albicans and coaggregation with pathogens). The involvement of electrostatic interactions and the influence of bacterial metabolic state in the binding of lactobacilli to the cell surface were also studied. Adherence to epithelial cells varied greatly among the Lactobacillus species and among different strains belonging to the same Lactobacillus species. The reduction in surface negative electric charge promoted the binding of several Lactobacillus strains to the cell membrane whereas lyophilization reduced the adhesion capacity of many isolates. The antimicrobial activity of lactobacilli culture supernatant fluids was not directly related to the production of H2O2.
Conclusions: Three strains (Lactobacillus brevis CD2, Lact. salivarius FV2 and Lact. gasseri MB335) showed optimal properties and were, therefore, selected for the preparation of vaginal tablets. The selected strains adhered to epithelial cells displacing vaginal pathogens; they produced high levels of H2O2, coaggregated with pathogens and inhibited the growth of G. vaginalis.
Significance and Impact of the Study: The dosage formulation developed in this study appears to be a good candidate for the probiotic prophylaxis and treatment of human vaginal infections
Characterization and selection of vaginal Lactobacillus strains for the preparation of vaginal tablets / LactoSpore® - Journal of Applied Microbiology 2002, 93, 884– 893 -P. Mastromarino, P. Brigidi, S. Macchia, L. Maggi, F. Pirovano, V. Trinchieri, U. Conte and D. Matteuzzi

Objective : To investigate the effects of Bacillus coagulans on immune functions, amine content of feces and ammonia content of intestinal tract in mice.Methods The clearance rate of charcoal particles,the weight of immune organs and hemolysin production were measured to study the effects of Bacillus coagulans and levamisole on nonspecific immunity,specific humoral immunity and immune organs in normal or immuno suppressive mice induced by hydrocortisone. Moreover, their influences on amine content of feces and ammonia content of intestinal tract in normal mice were determined. Results Levamisole could significantly increase the clearance rate of charcol particles but did not influence immune organ index in normal mice.Differently, Bacillus coagulans had little effect on the both indicators. However,they all could obviously elevate the clearance rate of charcoal particles and thymus organ index in immuno suppressive mice and notably raise hemolysin production in serum of SRBC- immunized mice.After administration of Bacillus coagulans for 21 days,amine content of feces and ammonia content of intestinal tract in mice were significantly lower than that control.Conclusion Bacillus coagulans could enhance immune functions in immun osuppressive mice,and reduce the amine and ammonia content in intestinal tract in normal mice.
The effects of Bacillus coagulans on immune functions,amine content of feces and ammonia content of intestinal tract in mice / Chinese Journal

Next generation of probiotic products
Although there are many probiotic products currently on the mar­ket, at present few contain spore-fonning bacteria. It is envisaged that the next generation of probiotic products will contain spore­forming bacteria, which have the benefit of being heat stable and can therefore be added to any food/drink without being degraded. These bacteria need to be compatible with the human gastrointesti­nal tract and known to be safe for human consumption.
The availability of probiotic spore-forming bacteria with demon­strated beneficial effects to the consumer is likely to result in an increase in the number of probiotic products on the market in the very near future
Spore-forming Bacteria / 1 page NutraFoods 2008, Simon Cutting, Paul Fraser, Katharine Payne

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease largely affecting low birth weight, premature infants. Once acquired, NEC is accompanied by significant mortality and morbid sequelae. Our understanding of the pathophysiology of NEC continues to evolve, and the development of NEC is likely multifactorial with resultant bowel injury mediated through a final, common inflammatory pathway. The predisposition for NEC appears to involve the interplay between intestinal integrity and function, enteral feeding and bacterial colonization, and regulation of the gastrointestinal and systemic inflammatory response. Commensal organisms or probiotics have been shown to be crucial in the development and modulation of each of these factors within the intestinal epithelium. As a result, probiotic supplementation has been proposed as a promising new intervention for the prevention of NEC. To understand the potential utility of probiotics in NEC, we will discuss: the components of gut defense; the role of the intestinal ecosystem in modulating immunity and inflammation; bacterial colonization patterns in the preterm infant compared with patterns seen in the healthy, full-term infant; the evidence for probiotic use in other populations and diseases; and finally, the evidence of probiotic use specific to the preterm infant and NEC.
KEYWORDS : probiotics, necrotizing enterocolitis, Lacobacillus, Bifidobacterium, Microflora, bacterial colonization, infant, prematurity
In conclusion : The cumulative evidence for probiotic supplementation in preterm infants for the prevention of NEC is very promising. Large, randomized controlled trials have shown effectiveness of probiotic supplementation in reducing the incidence of NEC. Just as encouraging, when NEC was present in the probiotic supplemented group of infants, NEC severity and mortality were decreased compared with controls. The fact that NEC could not be completely ameliorated with probiotic supplementation is consistent with the likely multifactorial etiology of NEC. However, this significant decrease in the number of NEC cases in addition to the decreased illness severity and mortality is worth pursuing. NEC severity is related to poor long-term neurodevelopmental outcomes,1 thus modification of the expression of NEC by probiotic supplementation may also improve long-term outcomes in NEC survivors. However, as additional trials move forward to study the role of probiotics in the prevention of NEC, concurrent evaluations for both short-term and long-term safety need to be included. Other ongoing issues and challenges include determining the most effective probiotic or combination of probiotics and dosing regimen. Heat-killed probiotics, probiotic DNA or proteins, or genetically modified probiotics have been shown to have similar benefits to the intestinal immune system as live probiotics. 104-107 As we learn more about the use of probiotic products in lieu of live, whole organisms, the FAO/WHO definition of probiotics may need to evolve. The definition offered by Salminen may, in fact, be more appropriate: “microbial cell preparations or components of microbial cells that have a beneficial effect on the health and well-being of the host.”108 These newer microbial preparations may provide alternatives to administering live organisms to ill, immunocompromised preterm infants while allowing for more precise delivery and dosing, and less likelihood of permanently manipulating the intestinal ecosystem and its resultant unknown long-term consequences.
Probiotics: Role in Pathophysiology and Prevention in Necrotizing Enterocolitis, Camilia R. Martin, MD,* and W. Allan Walker, MD, j.semperi. 2008. 01.006

We reviewed the evidence from human intervention studies for the health effects of probiotic bacteria, ie, live bacteria that survive passage through the gastrointestinal tract and have beneficial effects on the host. Of the 49 studies reviewed, 26 dealt with the prevention or treatment of diarrheal disease, 9 with the prevention of cancer or of the formation of carcinogens, 7 with the lowering of serum cholesterol, and 7 with the stimulation of the immune system. The most widely studied probiotic bacteria were Lactobacillus GG (22 studies), Lactobacillus acidophilus (16 studies), Bifidobacterium bifidum (6 studies), and Enterococcus faecium (7 studies). Intake of Lactobacillus GG consistently shortened the diarrheal phase of rotavirus infection by 1 d. However, evidence for the prevention by Lactobacillus GG and other probiotics of diarrhea due to viral or bacterial infections was less strong. Effects of probiotics on the immune system are inconclusive because of the variety of outcome variables reported. Cholesterol lowering by L. acidophilus was shown in some but not all studies; cholesterol lowering by E. faecium seems to be transient. Two studies of one research group showed a smaller recurrence of bladder tumors in patients after treatment with Lactobacillus casei; these results await confirmation. The production of mutagens after a meal might be reduced by the concomitant intake of probiotics, but the relevance of this finding is unclear. In conclusion, consumption of foods containing Lactobacillus GG may shorten the course of rotavirus infection. Other health effects of probiotic bacteria have not been well established. Well-designed placebo-controlled studies with validated outcome variables are needed todetermine the health effects of probiotics.
Effects of probiotic bacteria on diarrhea, lipid metabolism, and carcinogenesis: a review of papers published between 1988 and 1998 / Nicole M de Roos and Martijn B Katan - Am J Clin Nutr 2000;71:405–11, 2000 American Society for Clinical Nutrition

Background: Multiple organ dysfunction syndrome (MODS) is a major cause of mortality in intensive care units. A breakdown in gut barrier function and immune dysfunction are associated with the onset of MODS. Probiotic bacteria have been shown to modulate intestinal barrier and immune function.
Objective: This study assessed the efficacy of a probiotic compound in a viable and nonviable formulation in modulating intestinal permeability and immune function and preventing the onset of MODS in patients in the intensive care unit.
Design: A double-blind, randomized controlled trial was conducted in the intensive care unit of a tertiary care teaching hospital. Twenty- eight critically ill patients admitted to the intensive care unit were randomly assigned to receive 1 of 3 treatments daily for 7 d: 1) placebo, 2) viable probiotics, or 3) equivalent probiotic sonicates. MODS scores and systemic concentrations of immunoglobulin (Ig) A and IgG were measured on days 1, 4, and 7, and intestinal permeability measurements were taken daily.
Results: The patients responded to viable probiotics with a significantly larger increase in systemic IgA and IgG concentrations than in the patients who received placebo or sonicates (P less 0.05). MODS scores were not significantly affected by probiotic treatment. Over the study period, intestinal permeability decreased in most patients.
Conclusion: Patients receiving viable probiotics show a greater enhancement in immune activity than do patients receiving either placebo or probiotic bacterial sonicates.
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Effects of probiotic therapy in critically ill patients: a randomized, double-blind, placebo-controlled trial / LactoSpore® - Am J Clin Nutr 2007;85:816–23. Printed in USA.2007 American Society for Nutrition

The concentration of fecal mucin and the adhesion of specific probiotics and their combinations in the intestinal mucus of infants during and after rotavirus diarrhea and in healthy children were determined. Mucus was prepared from fecal samples from 20 infants during and after rotavirus diarrhea and from 10 healthy age-matched children. Mucin concentration was determined, and the adhesion of five probiotics Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Lactobacillus paracasei F19, Lactobacillus acidophilus LA5, and Bifidobacterium lactis Bb12—and their combinations was tested in vitro. The mean concentrations of fecal mucin during and after rotavirus diarrhea, 15.2 and 14.1 mg/g, were comparable to that in healthy children, 14.9 mg/g. The adherence of probiotics ranged from 1 to 34% in healthy subjects as indicated for the following strains: L. rhamnosus GG, 34%; B. lactis Bb12, 31%; L. acidophilus LA5, 4%; L. paracasei F19, 3%; and L. casei Shirota, 1% (P = 0.0001). The distinctive pattern of probiotic adherence was not influenced by rotavirus diarrhea. The adhesion of Bb12 in the presence of GG increased from 31 to 39% in healthy infants (P = 0.018) and in episodes of diarrhea increased from 26 to 44% (P = 0.001). Rotavirus diarrhea does not decrease the production of fecal mucin or with respect to the adhesion of probiotic bacteria tested in vitro. Combination of specific probiotic strains may enhance adherence in a synergistic manner. Optimal clinical application of these interactions may offer novel therapeutic guidelines for the treatment and prevention of gastrointestinal infections.
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Adherence of Probiotic Bacteria to Human Intestinal Mucus in Healthy Infants and during Rotavirus Infection / Turku Finland - CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 1071-412X/ 01 / CDLI.8.2.293– 296.2001 Mar. 2001, p. 293–296

Background: Irritable bowel syndrome is a gastrointestinal disorder of unknown aetiology. The effect of probiotics in this syndrome remains unclear.
Aim: To investigate whether a probiotic mixture containing Lactobacillus rhamnosus GG, L. rhamnosus LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii ssp. shermanii JS is effective in alleviating irritable bowel syndrome symptoms.
Methods: A total of 103 patients fulfilling the Rome I or II criteria took part in this 6-month, randomized, double- blind placebo-controlled trial. The patients received a probiotic capsule or a placebo capsule daily. Gastrointestinal symptoms and bowel habits were recorded.
Results: At the end the total symptom score (abdominal pain + distension + flatulence + borborygmi) was 7.7 (95% CI: )13.9 to )1.6) points lower in the probiotic group (P = 0.015). This represents a median reduction of 42% in the symptom score of the probiotic group compared with 6% in the placebo group. In individual symptoms, borborygmi was milder in the probiotic group (P = 0.008), and for the rest of the symptoms there was a non-significant trend.
Conclusions: The results indicate that this probiotic mixture is effective in alleviating irritable bowel syndrome symptoms. Considering the high prevalence of irritable bowel syndrome and the lack of effective therapies, even a slight reduction in symptoms could have positive public health consequences
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A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention / Helsinki / LactoSpore® - Aliment Pharmacol Ther 2005; 22: 387–394

One hundred and twelve newborn infants in rural India were randomized to receive a daily oral dose of 100 million Lactobacillus sporogenes or a placebo for one year. Morbidity was monitored each week for 12 months. Ninety four (84%) experienced diarrhoea due to rotavirus infection. The group fed L. sporogenes had fewer episodes of diarrhoea (3.4 +- 1.0 vs 8.6 +- 1.7 in the placebo group, p less 0.02) and less number of days of illness (13 +- 3 days vs 35 +- 5 days in the placebo group, p less 0.01). The episodes of diarrhoea were of shorter duration (3.6 +- 1.0 days vs 6.8 +- 1.1 days in the placebo group, p less 0.05). The number of infants who presented with mild to moderate dehydration was 11 in the treated group and 15 in the placebo group; the difference was statistically not significant (p more 0.05). There was a trend for body weight at one year to be higher (10.2 +- 0.2) in the treated group compared with infants who were controls (9.8 +- 0.3) but the difference was statistically not significant (p more 0.05). These observations suggest that the prophylactic feeding of Lactobacillus has a preventive effect on the incidence and duration of acute rotavirus diarrhoea
Keywords: Diarrhoea; Rotavirus; Lactobacillus; Morbidity.
Effect of Lactobacillus on the incidence and severity of acute rotavirus diarrhoea in infants. A prospective placebo-controlled double-blind study R.K. Chandra, M.D., F.R.C.P.C., Nutrition Research 22 (2002) 65–69

Short term hypolipidemic effects of oral Lactobacillus sporogenes (360 million spores/day) were studied in 17 patients (mean age 45.6 years; males 15, females 2) with type II hyperlipidemia in an open label fixed dose trial. Over a period of 3 months, significant reductions were observed in total cholesterol (330 +/- 55 mg% to 226 +/- 46 mg%, p less than 0.001) and LDL-cholesterol (267 +/- 58 mg% to 173 +/- 54 mg%, p less than 0.001). The HDL-cholesterol was marginally increased (43.6 +/- 7 mg% to 46.8 +/- 8.9 mg%, p less than 0.05). There was no change in serum triglyceride concentration. Total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios were significantly reduced after treatment (p less than 0.001). No adverse effect was noted. While the change in serum lipid levels on treatment was consistent with regard to total and LDL-cholesterol, it was not so in case of serum triglycerides and HDL-cholesterol. Oral Lactobacillus sporogenes therapy may prove to be an important hypolipidemic therapy after confirmation in larger trials.
Short term hypolipidemic effects of oral lactobacillus sporogenes therapy in patients with primary dyslipidemias / Screenshot abstract, Pant Hospital, New Delhi, Mohan JC, Arora R, Khalilullah M.

The use of probiotics to enhance intestinal health has been proposed for many years. Probiotics are traditionally defined as viable microorganisms that have a beneficial effect in the prevention and treatment of specific pathologic conditions when they are ingested. There is a relatively large volume of literature that supports the use of probiotics to prevent or treat intestinal disorders. However, the scientific basis of probiotic use has been firmly established only recently, and sound clinical studies have begun to be published. Currently, the best-studied probiotics are the lactic acid bacteria, particularly Lactobacillus sp. and Bifidobacterium sp. However, other organisms used as probiotics in humans include Escherichia coli, Streptococcus sp., Enterococcus sp., Bacteroides sp., Bacillus sp., Propionibacterium sp. and various fungi. Some probiotic preparations contain mixtures of more than one bacterial strain. Probiotics have been examined for their effectiveness in the prevention and treatment of a diverse spectrum of gastrointestinal disorders such as antibiotic-associated diarrhea (including Clostridium difficile–associated intestinal disease), infectious bacterial and viral diarrhea (including diarrhea caused by rotavirus, Shigella, Salmonella, enterotoxigenic E. coli, Vibrio cholerae and human immunodeficiency virus/ acquired immunodeficiency disorder, enteral feeding diarrhea, Helicobacter pylori gastroenteritis, sucrase maltase deficiency, inflammatory bowel disease, irritable bowel syndrome, small bowel bacterial overgrowth and lactose intolerance. Probiotics have been found to inhibit intestinal bacterial enzymes involved in the synthesis of colonic carcinogens. There are many mechanisms by which probiotics enhance intestinal health, including stimulation of immunity, competition for limited nutrients, inhibition of epithelial and mucosal adherence, inhibition of epithelial invasion and production of antimicrobial substances. Probiotics represent an exciting prophylactic and therapeutic advance, although additional investigations must be undertaken before their role in intestinal health can be delineated clearly.
The Role of Probiotic Cultures in the Control of Gastrointestinal Health, Rial D. Rolfe - Symposium: Probiotic Bacteria: Implications for Human Health, 2000 American Society for Nutritional Sciences.