Acute physiological effects following Bacillus subtilis DE111 oral ingestion – a randomised, double blinded, placebo-controlled study
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Previous studies using ileostomy samples from study participants demonstrated that the spore-forming probiotic Bacillus subtilis DE111® can germinate in the small intestine as early as 4 hours after ingestion. Metabolomics, proteomics and sequencing technologies, enabled further analysis of these samples for the presence of hypoglycaemic, hypolipidemic, antioxidant, anti-inflammatory and antihypertensive molecules. In the DE111 treatment group, the polyphenols trigonelline and 2,5-dihydroxybenzoic acid, orotic acid, the non-essential amino acid cystine and the lipokine 12,13-diHome were increased. DE111 also reduced acetylcholine levels in the ileostomy samples, and increased the expression of leucocyte recruiting proteins, antimicrobial peptides and intestinal alkaline phosphatases of the brush border in the small intestine. The combination of B. subtilis DE111 and the diet administered during the study increased the expression of the proteins phosphodiesterase ENPP7, ceramidase ASAH2 and the adipokine Zn-alpha-2-glycoprotein that are involved in fatty acid and lipid metabolism. Acute B. subtilis DE111 ingestion had limited detectable effect on the microbiome, with the main change being its increased presence. These findings support previous data suggesting a beneficial role of DE111 in digestion, metabolism, and immune health that appears to begin within hours of consumption.
-
Abedi, F., Razavi, B.M. and Hosseinzadeh, H., 2020. A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology, toxicology, and some pharmaceutical aspects. Phytotherapy Research 34: 729-741. https://doi.org/10.1002/ptr.6573
-
Anaya-Loyola, M.A., Enciso-Moreno, J.A., López-Ramos, J.E., García-Marín, G., Orozco Álvarez, M.Y., Vega-García, A.M., Mosqueda, J., García-Gutiérrez, D.G., Keller, D. and Pérez-Ramírez, I.F., 2019. Bacillus coagulans GBI-30, 6068 decreases upper respiratory and gastrointestinal tract symptoms in healthy Mexican scholar-aged children by modulating immune-related proteins. Food Research International 125: 108567. https://doi.org/10.1016/j.foodres.2019.108567
-
Bader, J., Albin, A. and Stahl, U., 2012. Spore-forming bacteria and their utilisation as probiotics. Beneficial Microbes 3: 67-75. https://doi.org/10.3920/BM2011.0039
-
Barbosa, T.M., Serra, C.R., La Ragione, R.M., Woodward, M.J. and Henriques, A.O., 2005. Screening for Bacillus isolates in the broiler gastrointestinal tract. Applied and Environmental Microbiology 71: 968-978. https://doi.org/10.1128/AEM.71.2.968-978.2005
-
Bingle, L., Cross, S.S., High, A.S., Wallace, W.A., Rassl, D., Yuan, G., Hellstrom, I., Campos, M.A. and Bingle, C.D., 2006. WFDC2 (HE4): A potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung. Respiratory Research 7: 61. https://doi.org/10.1186/1465-9921-7-61
-
Choi, J.H., Han, J., Theodoropoulos, P.C., Zhong, X., Wang, J., Medler, D., Ludwig, S., Zhan, X., Li, X., Tang, M., Gallagher, T., Yu, G. and Beutler, B., 2020. Essential requirement for nicastrin in marginal zone and B-1 B cell development. Proceedings of the National Academy of Sciences of the USA 117: 4894-4901. https://doi.org/10.1073/pnas.1916645117
-
Chowdhury, A.A., Gawali, N.B., Munshi, R. and Juvekar, A.R., 2017. Trigonelline insulates against oxidative stress, proinflammatory cytokines and restores BDNF levels in lipopolysaccharide induced cognitive impairment in adult mice. Metabolic Brain Disease 33: 681-691. https://doi.org/10.1007/S11011-017-0147-5
-
Clemente Plaza, N., Reig García-Galbis, M. and Martínez-Espinosa, R.M., 2018. Effects of the usage of l-cysteine (l-Cys) on human health. Molecules 23: 575. https://doi.org/10.3390/MOLECULES23030575
-
Colom, J., Freitas, D., Simon, A., Brodkorb, A., Buckley, M., Deaton, J. and Winger, A.M., 2021. Presence and germination of the probiotic Bacillus subtilis DE111® in the human small intestinal tract: a randomized, crossover, double-blind, and placebo-controlled study. Frontiers in Microbiology 12: 715863. https://doi.org/10.3389/FMICB.2021.715863
-
Cuentas, A.M., Deaton, J., Khan, S., Davidson, J. and Ardita, C., 2017. The effect of Bacillus subtilis DE111 on the daily bowel movement profile for people with occasional gastrointestinal irregularity. Journal of Probiotics and Health 5: 4. https://doi.org/10.4172/2329-8901.1000189
-
Deerland Probiotics and Enzymes, 2018. Generally recognized as safe (GRAS) conclusion for the use of Bacillus subtilis DE111 in foods. Deerland Probiotics and Enzymes, Cork, Ireland.
-
Doneanu, C.E., Chen, W., Mazzeo, J.R. and Ds, O.R., 2011. UPLC/MS monitoring of water-soluble vitamin Bs in cell culture media in minutes. Application note, Waters, Milford, MA, USA. Available at: https://tinyurl.com/bvycxycr
-
Elshaghabee, F.M.F., Rokana, N., Gulhane, R.D., Sharma, C. and Panwar, H., 2017. Bacillus as potential probiotics: status, concerns, and future perspectives. Frontiers in Microbiology 8: 1490. https://doi.org/10.3389/fmicb.2017.01490
-
Flo, T.H., Smith, K.D., Sato, S., Rodriguez, D.J., Holmes, M.A., Strong, R.K., Akira, S. and Aderem, A., 2004. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432: 917-921. https://doi.org/10.1038/nature03104
-
Freedman, K.E., Hill, J.L., Wei, Y., Vazquez, A.R., Grubb, D.S., Trotter, R.E., Wrigley, S.D., Johnson, S.A., Foster, M.T. and Weir, T.L., 2021. Examining the gastrointestinal and immunomodulatory effects of the novel probiotic Bacillus subtilis DE111. International Journal of Molecular Science 22: 2453. https://doi.org/10.3390/IJMS22052453
-
Gorelik, A., Liu, F., Illes, K. and Nagar, B., 2017. Crystal structure of the human alkaline sphingomyelinase provides insights into substrate recognition. Journal of Biological Chemistry 292: 7087. https://doi.org/10.1074/JBC.M116.769273
-
Gregersen, H., Kwiatek, M.A., Schwizer, W. and Tutuian, R., 2007. Contribution of sensitivity, volume and tone to visceral perception in the upper gastrointestinal tract in man: emphasis on testing. Neurogastroenterology and Motility 19: 47-61. https://doi.org/10.1111/j.1365-2982.2006.00845.x
-
Gupta, R.C., Doss, R.B., Garg, R.C., Srivastava, A., Lall, R. and Sinha, A., 2021. Fenugreek: multiple health benefits. In: Gupta, R.C., Lall, R. and Srivastava, A. (eds.) Nutraceuticals. Academic Press, Cambridge, MA, USA, pp. 585-602. https://doi.org/10.1016/B978-0-12-821038-3.00037-9
-
Hanifi, A., Culpepper, T., Mai, V., Anand, A., Ford, A.L., Ukhanova, M., Christman, M., Tompkins, T.A. and Dahl, W.J., 2015. Evaluation of Bacillus subtilis R0179 on gastrointestinal viability and general wellness: a randomised, double-blind, placebo-controlled trial in healthy adults. Beneficial Microbes 6: 19-27. https://doi.org/10.3920/BM2014.0031
-
Hassan, M.I., Waheed, A., Yadav, S., Singh, T.P. and Ahmad, F., 2008. Zinc alpha 2-glycoprotein: a multidisciplinary protein. Molecular Cancer Research 6: 892-906. https://doi.org/10.1158/1541-7786.MCR-07-2195
-
Hatanaka, M., Yamamoto, K., Suzuki, N., Iio, S., Takara, T., Morita, H., Takimoto, T. and Nakamura, T., 2018. Effect of Bacillus subtilis C-3102 on loose stools in healthy volunteers. Beneficial Microbes 9: 357-365. https://doi.org/10.3920/BM2017.0103
-
Hill, C., Guarner, F., Reid, G., Gibson, G.R., Merenstein, D.J., Pot, B., Morelli, L., Canani, R.B., Flint, H.J., Salminen, S., Calder, P.C. and Sanders, M.E., 2014. Expert consensus document: The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology and Hepatology 11: 506-514. https://doi.org/10.1038/nrgastro.2014.66
-
Holzer, P. and Farzi, A., 2014. Neuropeptides and the microbiota-gut-brain axis. In: Lyte, M. and Cryan, J.F. (eds.) Microbial endocrinology: the microbiota-gut-brain axis in health and disease. Springer New York, New York, NY, USA, pp. 195-219. https://doi.org/10.1007/978-1-4939-0897-4_9
-
Horosheva, T.V., Vodyanoy, V. and Sorokulova, I., 2014. Efficacy of Bacillus probiotics in prevention of antibiotic-associated diarrhoea: a randomized, double-blind, placebo-controlled clinical trial. JMM Case Reports 1: e004036. https://doi.org/10.1099/jmmcr.0.004036
-
Hoyles, L., Honda, H., Logan, N.A., Halket, G., La Ragione, R.M. and McCartney, A.L., 2012. Recognition of greater diversity of Bacillus species and related bacteria in human faeces. Research in Microbiology 163: 3-13. https://doi.org/10.1016/j.resmic.2011.10.004
-
Inatsu, Y., Nakamura, N., Yuriko, Y., Fushimi, T., Watanasiritum, L. and Kawamoto, S., 2006. Characterization of Bacillus subtilis strains in Thua nao, a traditional fermented soybean food in northern Thailand. Letters in Applied Microbiology 43: 237-242. https://doi.org/10.1111/j.1472-765X.2006.01966.x
-
Khalesi, S., Bellissimo, N., Vandelanotte, C., Williams, S., Stanley, D. and Irwin, C., 2019. A review of probiotic supplementation in healthy adults: helpful or hype? European Journal of Clinical Nutrition 73: 24-37. https://doi.org/10.1038/s41430-018-0135-9
-
Kulak, N.A., Pichler, G., Paron, I., Nagaraj, N. and Mann, M., 2014. Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells. Nature Methods 11: 319-324. https://doi.org/10.1038/nmeth.2834
-
Lallès, J.P., 2014. Intestinal alkaline phosphatase: novel functions and protective effects. Nutrition Reviews 72: 82-94. https://doi.org/10.1111/NURE.12082
-
Lefevre, M., Racedo, S.M., Denayrolles, M., Ripert, G., Desfougères, T., Lobach, A.R., Simon, R., Pélerin, F., Jüsten, P. and Urdaci, M.C., 2017. Safety assessment of Bacillus subtilis CU1 for use as a probiotic in humans. Regulatory Toxicology and Pharmacology 83: 54-65. https://doi.org/10.1016/j.yrtph.2016.11.010
-
Lefevre, M., Racedo, S.M., Ripert, G., Housez, B., Cazaubiel, M., Maudet, C., Jüsten, P., Marteau, P. and Urdaci, M.C., 2015. Probiotic strain Bacillus subtilis CU1 stimulates immune system of elderly during common infectious disease period: A randomized, doubleblind placebo-controlled study. Immunity and Ageing 12: 24. https://doi.org/10.1186/s12979-015-0051-y
-
Löffler, M., Carrey, E.A. and Zameitat, E., 2015. Orotic acid, more than just an intermediate of pyrimidine de novo synthesis. Journal of Genetics and Genomics 42: 207-219. https://doi.org/10.1016/J.JGG.2015.04.001
-
Maher, M., 2019. Tolerance and Effect of a Probiotic Supplement Delivered in Capsule Form. Food Nutr. Sci. 10, 626-634. https://doi.org/10.4236/fns.2019.106046
-
Mehta, D., De Souza, A., Jadhav, S. and Devale, M., 2020. an open labeled, placebo controlled trial to evaluate the role of probiotics – Bacillus subtilis HU58 and Bacillus coagulans SC208 on antibiotic associated diarrhoea in humans. Biomedical Journal of Scientific & Technical Research 29: 22679-22684. https://doi.org/10.26717/bjstr.2020.29.004839
-
Meyer, J.E., Harder, J., Sipos, B., Maune, S., Klöppel, G., Bartels, J., Schröder, J.M. and Gläser, R., 2008. Psoriasin (S100A7) is a principal antimicrobial peptide of the human tongue. Mucosal Immunology 1: 239-243. https://doi.org/10.1038/MI.2008.3
-
Paytuví-Gallart, A., Sanseverino, W. and Winger, A.M., 2020. Daily intake of probiotic strain Bacillus subtilis DE111 supports a healthy microbiome in children attending day-care. Beneficial Microbes 11: 611-620. https://doi.org/10.3920/BM2020.0022
-
Penet, C., Kramer, R., Little, R., Spears, J.L., Parker, J., Iyer, J.K., Guthrie, N. and Evans, M., 2021. A randomized, double-blind, placebo-controlled, parallel study evaluating the efficacy of Bacillus subtilis MB40 to reduce abdominal discomfort, gas, and bloating. Alternative Therapies in Health and Medicine 27(S1): 146-157.
'A randomized, double-blind, placebo-controlled, parallel study evaluating the efficacy of Bacillus subtilis MB40 to reduce abdominal discomfort, gas, and bloating ' () 27 Alternative Therapies in Health and Medicine : 146 -157.
-
Rappsilber, J., Mann, M. and Ishihama, Y., 2007. Protocol for micropurification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nature Protocols 28: 1896-1906. https://doi.org/10.1038/nprot.2007.261
-
Ray, P., Sanchez, C., O’Sullivan, D.J. and McKay, L.L., 2000. Classification of a bacterial isolate, from pozol, exhibiting antimicrobial activity against several gram-positive and gram-negative bacteria, yeasts, and molds. Journal of Food Protection 63: 1123-1132. https://doi.org/10.4315/0362-028X-63.8.1123
-
Ridlon, J.M., Kang, D.J., Hylemon, P.B. and Bajaj, J.S., 2014. Bile acids and the gut microbiome. Current Opinion in Gastroenterology 30: 332. https://doi.org/10.1097/MOG.0000000000000057
-
Sarkar, A., Lehto, S.M., Harty, S., Dinan, T.G., Cryan, J.F. and Burnet, P.W.J., 2016. Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends in Neuroscience 39: 763-781. https://doi.org/10.1016/j.tins.2016.09.002
-
Singh, S.B., Carroll-Portillo, A., Coffman, C., Ritz, N.L. and Lin, H.C., 2020. Intestinal alkaline phosphatase exerts anti-inflammatory effects against lipopolysaccharide by inducing autophagy. Science Reports 10: 3107. https://doi.org/10.1038/s41598-020-59474-6
-
Slivnik, M., Crnigoj Kristan, K., Cebron Lipovec, N., Locatelli, I., Orel, R. and Winger, A.M., 2020. Effect of daily Bacillus subtilis DE111 ® intake on gastrointestinal health and respiratory infections in children attending day-care: a randomised, parallel, double-blind, placebo-controlled study. Journal of Probiotics and Health 8: 225. https://doi.org/10.35248/2329-8901.20.8:225
-
Stanford, K.I., Lynes, M.D., Takahashi, H., Baer, L.A., Arts, P.J., May, F.J., Lehnig, A.C., Middelbeek, R.J.W., Richard, J.J., So, K., Chen, E.Y., Gao, F., Narain, N.R., Distefano, G., Shettigar, V.K., Hirshman, M.F., Ziolo, M.T., Kiebish, M.A., Tseng, Y.H., Coen, P.M. and Goodyear, L.J., 2018. 12,13-diHOME: An exercise-induced lipokine that increases skeletal muscle fatty acid uptake. Cell Metabolism 27: 1111-1120.e3. https://doi.org/10.1016/J.CMET.2018.03.020
-
Suva, M., Sureja, V.V. and Kheni, D.D., 2016. Novel insight on probiotic Bacillus subtilis: mechanism of action and clinical applications. Journal of Current Research in Scientific Medicine 2: 65-72. https://doi.org/10.4103/2455-3069.198381
-
Takimoto, T., Hatanaka, M., Hoshino, T., Takara, T., Tanaka, K., Shimizu, A., Morita, H. and Nakamura, T., 2018. Effect of Bacillus subtilis C-3102 on bone mineral density in healthy postmenopausal Japanese women: A randomized, placebo-controlled, double-blind clinical trial. Bioscience of Microbiota, Food and Health 37: 87-96. https://doi.org/10.12938/bmfh.18-006
-
Tohda, C., Kuboyama, T. and Komatsu, K., 2005. Search for natural products related to regeneration of the neuronal network. NeuroSignals 14: 34-45. https://doi.org/10.1159/000085384
-
Toohey, J.C., Townsend, J.R., Johnson, S.B., Toy, A.M., Vantrease, W.C., Bender, D., Crimi, C.C., Stowers, K.L., Ruiz, M.D., VanDusseldorp, T.A., Feito, Y. and Mangine, G.T., 2020. Effects of probiotic (Bacillus subtilis) supplementation during offseason resistance training in female division I athletes. Journal of Strength and Conditioning Research 34: 3173-3181. https://doi.org/10.1519/JSC.0000000000002675
-
Townsend, J.R., Bender, D., Vantrease, W.C., Sapp, P.A., Toy, A.M., Woods, C.A. and Johnson, K.D., 2018. Effects of probiotic (Bacillus subtilis DE111) supplementation on immune function, hormonal status, and physical performance in division I baseball players. Sport 6: 70. https://doi.org/10.3390/SPORTS6030070
-
Trotter, R.E., Vazquez, A.R., Grubb, D.S., Freedman, K.E., Grabos, L.E., Jones, S., Gentile, C.L., Melby, C.L., Johnson, S.A. and Weir, T.L., 2020. Bacillus subtilis DE111 intake may improve blood lipids and endothelial function in healthy adults. Beneficial Microbes 11: 621-630. https://doi.org/10.3920/BM2020.0039
-
Vasdev, S., Singal, P. and Gill, V., 2009. The antihypertensive effect of cysteine. International Journal of Angiology 18: 7-21. https://doi.org/10.1055/S-0031-1278316
-
Wang, J. and Fung, D.Y.C., 1996. Alkaline-fermented foods: a review with emphasis on pidan fermentation. Critical Reviews in Microbiology 22: 101-138. https://doi.org/10.3109/10408419609106457
-
Wang, Siwen, Song, R., Wang, Z., Jing, Z., Wang, Shaoxiong and Ma, J., 2018. S100A8/A9 in inflammation. Frontiers in Immunology 9: 1298. https://doi.org/10.3389/fimmu.2018.01298
-
Yajima, T., Inoue, R., Matsumoto, M. and Yajima, M., 2011. Nonneuronal release of ACh plays a key role in secretory response to luminal propionate in rat colon. Journal of Physiology 589: 953-962. https://doi.org/10.1113/jphysiol.2010.199976
-
Yong, S.J., Tong, T., Chew, J. and Lim, W.L., 2020. Antidepressive mechanisms of probiotics and their therapeutic potential. Frontiers in Neuroscience 13: 1361. https://doi.org/10.3389/fnins.2019.01361
-
Yu, G., Wang, L.G., Han, Y. and He, Q.Y., 2012. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16: 284. https://doi.org/10.1089/OMI.2011.0118
-
Yu, G., Wang, L.G., Yan, G.R. and He, Q.Y., 2015. DOSE: an R/Bioconductor package for disease ontology semantic and enrichment analysis. Bioinformatics 31: 608-609. https://doi.org/10.1093/BIOINFORMATICS/BTU684
-
Yuab, G. and He, Q.-Y., 2016. ReactomePA: an R/Bioconductor package for reactome pathway analysis and visualization. Molecular Biosystems 12: 477-479. https://doi.org/10.1039/x0xx00000x
-
Zhao, Y. and Yu, Y.-B., 2016. Intestinal microbiota and chronic constipation. SpringerPlus 5: 1130. https://doi.org/10.1186/s40064-016-2821-1
-
Zhou, J., Chan, L. and Zhou, S., 2012. Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease. Current Medicinal Chemistry 19: 3523-3531. https://doi.org/10.2174/092986712801323171
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Acute physiological effects following Bacillus subtilis DE111 oral ingestion – a randomised, double blinded, placebo-controlled study
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Previous studies using ileostomy samples from study participants demonstrated that the spore-forming probiotic Bacillus subtilis DE111® can germinate in the small intestine as early as 4 hours after ingestion. Metabolomics, proteomics and sequencing technologies, enabled further analysis of these samples for the presence of hypoglycaemic, hypolipidemic, antioxidant, anti-inflammatory and antihypertensive molecules. In the DE111 treatment group, the polyphenols trigonelline and 2,5-dihydroxybenzoic acid, orotic acid, the non-essential amino acid cystine and the lipokine 12,13-diHome were increased. DE111 also reduced acetylcholine levels in the ileostomy samples, and increased the expression of leucocyte recruiting proteins, antimicrobial peptides and intestinal alkaline phosphatases of the brush border in the small intestine. The combination of B. subtilis DE111 and the diet administered during the study increased the expression of the proteins phosphodiesterase ENPP7, ceramidase ASAH2 and the adipokine Zn-alpha-2-glycoprotein that are involved in fatty acid and lipid metabolism. Acute B. subtilis DE111 ingestion had limited detectable effect on the microbiome, with the main change being its increased presence. These findings support previous data suggesting a beneficial role of DE111 in digestion, metabolism, and immune health that appears to begin within hours of consumption.
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