Effect of Bacillus subtilis C-3102 on loose stools in healthy volunteers

Hatanaka, Minoru; Yamamoto, Kentaro; Suzuki, Nobuhiro; Iio, Shin-ichiro; Takara, Tsuyoshi; Morita, Hiroto; Takimoto, Takuou; Nakamura, T.

doi:10.3920/bm2017.0103

Cited by 35 publications

(27 citation statements)

References 15 publications

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“…Analysis of the composition of the in vitro human colonic microbiota model by next generation sequencing. Microbiota composition was determined with a MiSeq V2 kit (Illumina, San Diego, CA, USA), as described previously 15 .…”

Section: Growth Activity Ofmentioning

confidence: 99%

“…In addition, ingestion of C-3102 at 8.0 × 10 8 colony forming units (cfu)/day for 8 days in human subjects increased the relative abundance of the genus Bifidobacterium and decreased the number of Enterobacteriaceae 14 . Recently, it has been reported that ingestion of C-3102 at 2.2 × 10 9 cfu/day for 8 weeks improved loose stool symptoms in adults 15 , and ingesting 3.4 × 10 9 cfu/day for 24 weeks increased the abundance of Bifidobacterium in postmenopausal women 16 . Therefore, C-3102 has the potential to modulate the gut microbiota to improve fecal properties in humans.…”

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confidence: 99%

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Effective bifidogenic growth factors cyclo-Val-Leu and cyclo-Val-Ile produced by Bacillus subtilis C-3102 in the human colonic microbiota model

Hatanaka¹,

Morita²,

Aoyagi³

et al. 2020

Sci Rep

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Bifidobacterium species are known to fulfill important functions within the human colon. Thus, stimulating the activity of bifidobacteria is important to maintain host health. We revealed that culture supernatants of Bacillus subtilis C-3102 (referred to as C-3102) stimulated the growth of Bifidobacterium species. In this study, we isolated and identified six bifidogenic growth factors, which were cyclo (D-Val-D-Ile), cyclo (L-Val-D-Ile), cyclo (D-Val-L-Ile), cyclo (L-Val-L-Ile), cyclo (D-Val-L-Leu) and cyclo (L-Val-L-Leu). These six cyclic dipeptides increased the growth of Bifidobacterium species and had no effect on potentially harmful gut organisms. Moreover, supplementation with a mixture of these six cyclic dipeptides significantly increased the abundance of microorganisms related to the genus Bifidobacterium in a human colonic microbiota model culture system, although supplementation with a single type of dipeptide had no effect. These results show that cyclic dipeptides containing Val-Leu and Val-Ile produced by C-3102 could serve as bifidogenic growth factors in the gut microbial community. In the past few decades, the human gut microbiota has been reported to play an important role in the promotion of health, and several illnesses are known to be influenced by imbalances of gut microbiota 1. Therefore, manipulation of the gut microbiota is a clinical target for the treatment of gut microbiota-related diseases 2. Bifidobacterial populations belonging to the phylum Actinobacteria are the most dominant microbial group present in the healthy infant gut 3. The population of Bifidobacterium in the human gut decreases gradually from infancy to childhood, then remains relatively stable during an adult's life, and ultimately decreases in old age 4. Numerous health-promoting effects have been ascribed to certain strains of the genus Bifidobacterium, which are widely used as probiotics 5. For instance, one Japanese study reported that allergic children had less bifidobacteria compared to non-allergic children at an early stage, 4 months of age, and prenatal supplementation of bifidobacteria to mothers and postnatal supplementation to infants reduced the risk of allergies 6. It has also been reported that ingestion of Bifidobacterium breve has an anti-obesity effect in mice fed a high-fat diet 7 , and ingestion of Bifidobacterium infantis was effective in relieving symptom of irritable bowel syndrome in women 8,9. These findings suggest an important role for bifiodobacteria in regulating intestinal homeostasis. Some Bacillus subtilis strains are safe, survive passage through the human gastrointestinal tract, and do not induce any undesirable physiological effects in human subjects 10,11. One reported probiotic effect of B. subtilis was associated with inhibiting the growth of pathogenic bacteria such as Salmonella enterica to improve the growth of beneficial bacteria such as lactobacilli 12. In our previous study, B. subtilis C-3102 (hereinafter, referred to as C-3102) was tested using the TNO Gastro-Intestinal Mod...

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Section: Growth Activity Ofmentioning

confidence: 99%

mentioning

confidence: 99%

Effective bifidogenic growth factors cyclo-Val-Leu and cyclo-Val-Ile produced by Bacillus subtilis C-3102 in the human colonic microbiota model

Hatanaka¹,

Morita²,

Aoyagi³

et al. 2020

Sci Rep

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“…Based on prior testing of probiotic B. subtilis, no safety concerns were expected even at high doses [26][27][28][29][30][31][32]. Therefore, dosage levels for the study were chosen based on the intended dose for the final product, namely 10 9 CFU.…”

Section: Methodsmentioning

confidence: 99%

LyophilizedB. subtilisZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study In Wistar Rats

Barla¹,

Kannan²,

Kumar³

et al. 2019

Preprint

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A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strain B. subtilis ZB183. Lyophilized spores at doses of 10 9 , 10 10 , and 10 11 CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days. B.Subtilis ZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 10 10 and 10 11 CFU/kg/day doses without an increase in total protein in males or females and was considered a non-adverse effect. The "No Observed Adverse Effect Level (NOAEL)" is defined at the highest dose of 10 11 CFU/kg body weight/day for lyophilized B.Subtilis ZB183 Spores under the test conditions employed.

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“…Fecal samples were collected at 0 and 12 weeks, and fecal DNA was extracted by the bead beating method as previously described [34]. Amplification of the 16S rRNA sequence was performed with the primer set of Tru357F (5 -CGCTCTTCCGATCTCTG TACGGRAGGCAGCAG-3 ) and Tru806R (5 -CGCTCTTCCGATCTGACGGACTACHVGGGTWTCTAAT-3 ) as described previously [35].…”

Section: Analysis Of Fecal Microbiotamentioning

confidence: 99%

Daily Intake of Paraprobiotic Lactobacillus amylovorus CP1563 Improves Pre-Obese Conditions and Affects the Gut Microbial Community in Healthy Pre-Obese Subjects: A Double-Blind, Randomized, Placebo-Controlled Study

Sugawara¹,

Sawada²,

Yanagihara³

et al. 2020

Microorganisms

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Despite the fact that gut microbiota is closely associated with obesity, few studies have focused on the influences of paraprobiotics as food ingredients on both obesity prevention and the gut microbial community. In this study, we evaluated the effects of fragmented Lactobacillus amylovorus CP1563 (CP1563) as a paraprobiotic for obesity prevention and investigated its effects on the gut microbial community in pre-obese subjects. One hundred sixty-nine healthy subjects with a body mass index from 25.0 to 29.9 kg/m2 ingested beverages with or without the fragmented CP1563 containing 10-hydroxyoctadecanoic acid (10-HOA) for 12 weeks. The changes in abdominal, total, visceral, and subcutaneous fatty areas were significantly lower in the CP1563-10-HOA group than in the placebo group at 12 weeks. Furthermore, 16S rRNA gene sequencing of fecal DNA revealed that the changes in the abundances of the genera Roseburia and Lachnospiraceae;g were significantly greater in the CP1563-10-HOA group than in the placebo group, and the changes in the abundances of the genus Collinsella was significantly smaller in the CP1563-10HOA group than in the placebo group. Our results showed that continuous ingestion of the fragmented CP1563 containing 10-HOA reduced abdominal body fat and affected the gut microbial community in pre-obese healthy subjects. Our findings may contribute to the understanding of the relationship between the anti-obesity effect of paraprobiotics and gut microbiota.

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Effect of Bacillus subtilis C-3102 on loose stools in healthy volunteers

Cited by 35 publications

References 15 publications

Effective bifidogenic growth factors cyclo-Val-Leu and cyclo-Val-Ile produced by Bacillus subtilis C-3102 in the human colonic microbiota model

Effective bifidogenic growth factors cyclo-Val-Leu and cyclo-Val-Ile produced by Bacillus subtilis C-3102 in the human colonic microbiota model

LyophilizedB. subtilisZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study In Wistar Rats

Daily Intake of Paraprobiotic Lactobacillus amylovorus CP1563 Improves Pre-Obese Conditions and Affects the Gut Microbial Community in Healthy Pre-Obese Subjects: A Double-Blind, Randomized, Placebo-Controlled Study

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