Next-Generation Probiotics: health-promoting bacteria of the human gut
Abstract
In recent years, a vast number of human diseases have been correlated with gut microbiota dysbiosis. The development of modern methods in molecular microbiology, such as the culturomics approach, as well as various multi-omics methods like next generation sequencing, transcriptomics and metabolomics analysis, coupled with large data sets correlation analysis, enabled the cultivation and characterization of novel anaerobic hitherto uncultivated Next-Generation Probiotics. In addition, the results of host-microbe interactions studies helped to reveal the mechanisms involved in the beneficial effects of Next-Generation Probiotics. Eventually, the obtained data on Next-Generation Probiotics will help to broaden the scientific knowledge on these bacteria, in terms of both their safety and health-promoting effects, unravel opportunities for the development of novel therapeutic strategies for prevention and treatment of tumors, metabolic, neuropsychiatric and other diseases, with the aim of relieving the symptoms of the diseases and increasing the quality of life for patients and their families. So far, the best characterized probiotics of the new generation are Akkermansia muciniphila, Faecalibacterium prauznitzii and Bacteroides fragilis.
References
Dinić M, Lukić J, Djokić J, Milenković M, Strahinić I, Golić N, et al. Lactobacillus fermentum Postbiotic-induced Autophagy as Potential Approach for Treatment of Acetaminophen Hepatotoxicity. Front Microbiol. 2017;8:594.
Dinić M, Pecikoza U, Djokić J, Stepanović-Petrović R, Milenković M, Stevanović M, et al. Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats. Front Pharmacol. 2018;9:1.
Mihailović M, Živković M, Jovanović JA, Tolinački M, Sinadinović M, Rajić J, et al. Oral administration of probiotic Lactobacillus paraplantarum BGCG11 attenuates diabetes-induced liver and kidney damage in rats. J Funct Foods. 2017;38:427–37.
Popović N, Djokić J, Brdarić E, Dinić M, Terzić-Vidojević A, Golić N, et al. The Influence of Heat-Killed Enterococcus faecium BGPAS1-3 on the Tight Junction Protein Expression and Immune Function in Differentiated Caco-2 Cells Infected with Listeria monocytogenes ATCC 19111. Front Microbiol. 2019;10:412.
Sokovic Bajic S, Djokic J, Dinic M, Veljovic K, Golic N, Mihajlovic S, et al. GABA-Producing Natural Dairy Isolate from Artisanal Zlatar Cheese Attenuates Gut Inflammation and Strengthens Gut Epithelial Barrier in vitro. Front Microbiol. 2019;10:527.
Bajić SS, Đokić J, Dinić M, Tomić S, Popović N, Brdarić E, et al. GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro. Sci Rep. 2020;10(1):1347.
Amara AA, Shibl A. Role of Probiotics in health improvement, infection control and disease treatment and management. Saudi Pharm J SPJ. 2015;23(2):107–14.
Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915–20.
Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016;375(24):2369–79.
Fischbach MA. Microbiome: Focus on Causation and Mechanism. Cell. 2018;174(4):785–90.
Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, et al. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiol Mol Biol Rev MMBR. 2017;81(4):e00036-17.
Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823–36.
Langille MGI. Exploring Linkages between Taxonomic and Functional Profiles of the Human Microbiome. mSystems. 2018;3(2):e00163-17.
Martín R, Langella P. Emerging Health Concepts in the Probiotics Field: Streamlining the Definitions. Front Microbiol. 2019;10:1047.
Wegh CAM, Geerlings SY, Knol J, Roeselers G, Belzer C. Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond. Int J Mol Sci. 2019;20(19):4673.
Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54(Pt 5):1469–76.
Karcher N, Nigro E, Punčochář M, Blanco-Míguez A, Ciciani M, Manghi P, et al. Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly. Genome Biol. 2021;22(1):209.
Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat Rev Endocrinol. 2013;9(1):13–27.
Erem C, Arslan C, Hacihasanoglu A, Deger O, Topbas M, Ukinc K, et al. Prevalence of obesity and associated risk factors in a Turkish population (trabzon city, Turkey). Obes Res. 2004;12(7):1117–27.
Sonnenburg JL, Bäckhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016;535(7610):56–64.
Indiani CMDSP, Rizzardi KF, Castelo PM, Ferraz LFC, Darrieux M, Parisotto TM. Childhood Obesity and Firmicutes/Bacteroidetes Ratio in the Gut Microbiota: A Systematic Review. Child Obes Print. 2018;14(8):501–9.
Yang M, Bose S, Lim S, Seo J, Shin J, Lee D, et al. Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation. Microorganisms. 2020;8(9):1413.
Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066–71.
Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107–13.
Ashrafian F, Shahriary A, Behrouzi A, Moradi HR, Keshavarz Azizi Raftar S, Lari A, et al. Akkermansia muciniphila-Derived Extracellular Vesicles as a Mucosal Delivery Vector for Amelioration of Obesity in Mice. Front Microbiol. 2019;10:2155.
EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA), Turck D, Bohn T, Castenmiller J, De Henauw S, Hirsch-Ernst KI, et al. Safety of pasteurised Akkermansia muciniphila as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2021;19(9):e06780.
Weir GC, Bonner-Weir S. Five Stages of Evolving Beta-Cell Dysfunction During Progression to Diabetes. Diabetes. 2004;53(suppl_3):S16–21.
Zhang X, Shen D, Fang Z, Jie Z, Qiu X, Zhang C, et al. Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance. PLOS ONE. 2013;8(8):e71108.
Yassour M, Lim MY, Yun HS, Tickle TL, Sung J, Song YM, et al. Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med. 2016;8(1):17.
Medina-Vera I, Sanchez-Tapia M, Noriega-López L, Granados-Portillo O, Guevara-Cruz M, Flores-López A, et al. A dietary intervention with functional foods reduces metabolic endotoxaemia and attenuates biochemical abnormalities by modifying faecal microbiota in people with type 2 diabetes. Diabetes Metab. 2019;45(2):122–31.
Gurung M, Li Z, You H, Rodrigues R, Jump DB, Morgun A, et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine. 2020;51:102590.
Deng L, Ou Z, Huang D, Li C, Lu Z, Liu W, et al. Diverse effects of different Akkermansia muciniphila genotypes on Brown adipose tissue inflammation and whitening in a high-fat-diet murine model. Microb Pathog. 2020;147:104353.
Yoon HS, Cho CH, Yun MS, Jang SJ, You HJ, Kim JH, et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice. Nat Microbiol. 2021;6(5):563–73.
Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA, Hanyaloglu AC, et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes. 2015;39(3):424–9.
Xia J, Lv L, Liu B, Wang S, Zhang S, Wu Z, et al. Akkermansia muciniphila Ameliorates Acetaminophen-Induced Liver Injury by Regulating Gut Microbial Composition and Metabolism. Microbiol Spectr. 2022;10(1):e0159621.
Huang X, Liu G, Guo J, Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci. 2018;14(11):1483–96.
Lukovac S, Belzer C, Pellis L, Keijser BJ, de Vos WM, Montijn RC, et al. Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. mBio. 2014;5(4):e01438-14.
Lichtenstein L, Berbée JFP, van Dijk SJ, van Dijk KW, Bensadoun A, Kema IP, et al. Angptl4 upregulates cholesterol synthesis in liver via inhibition of LPL- and HL-dependent hepatic cholesterol uptake. Arterioscler Thromb Vasc Biol. 2007;27(11):2420–7.
Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. 2009;461(7268):1282–6.
Alex S, Lange K, Amolo T, Grinstead JS, Haakonsson AK, Szalowska E, et al. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor γ. Mol Cell Biol. 2013;33(7):1303–16.
Waldecker M, Kautenburger T, Daumann H, Busch C, Schrenk D. Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon. J Nutr Biochem. 2008;19(9):587–93.
Fusunyan RD, Quinn JJ, Fujimoto M, MacDermott RP, Sanderson IR. Butyrate Switches the Pattern of Chemokine Secretion by Intestinal Epithelial Cells through Histone Acetylation. Mol Med. 1999;5(9):631–40.
Alenghat T, Osborne LC, Saenz SA, Kobuley D, Ziegler CGK, Mullican SE, et al. Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature. 2013;504(7478):153–7.
Zheng M, Han R, Yuan Y, Xing Y, Zhang W, Sun Z, et al. The role of Akkermansia muciniphila in inflammatory bowel disease: Current knowledge and perspectives. Front Immunol. 2023;13:1089600.
Ganesh BP, Klopfleisch R, Loh G, Blaut M. Commensal Akkermansia muciniphila Exacerbates Gut Inflammation in Salmonella Typhimurium-Infected Gnotobiotic Mice. PLOS ONE. 2013;8(9):e74963.
Ring C, Klopfleisch R, Dahlke K, Basic M, Bleich A, Blaut M. Akkermansia muciniphila strain ATCC BAA-835 does not promote short-term intestinal inflammation in gnotobiotic interleukin-10-deficient mice. Gut Microbes. 2019;10(2):188–203.
Liu Q, Lu W, Tian F, Zhao J, Zhang H, Hong K, et al. Akkermansia muciniphila Exerts Strain-Specific Effects on DSS-Induced Ulcerative Colitis in Mice. Front Cell Infect Microbiol. 2021;11:698914.
Wang L, Tang L, Feng Y, Zhao S, Han M, Zhang C, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8+ T cells in mice. Gut. 2020;69(11):1988–97.
Fan L, Xu C, Ge Q, Lin Y, Wong CC, Qi Y, et al. A. Muciniphila Suppresses Colorectal Tumorigenesis by Inducing TLR2/NLRP3-Mediated M1-Like TAMs. Cancer Immunol Res. 2021;9(10):1111–24.
Meng X, Zhang J, Wu H, Yu D, Fang X. Akkermansia muciniphila Aspartic Protease Amuc_1434* Inhibits Human Colorectal Cancer LS174T Cell Viability via TRAIL-Mediated Apoptosis Pathway. Int J Mol Sci. 2020;21(9):3385.
Meng X, Wang W, Lan T, Yang W, Yu D, Fang X, et al. A Purified Aspartic Protease from Akkermansia Muciniphila Plays an Important Role in Degrading Muc2. Int J Mol Sci. 2019;21(1):72.
Chen Z, Qian X, Chen S, Fu X, Ma G, Zhang A. Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice. J Immunol Res. 2020;2020:2969287.
Shi L, Sheng J, Chen G, Zhu P, Shi C, Li B, et al. Combining IL-2-based immunotherapy with commensal probiotics produces enhanced antitumor immune response and tumor clearance. J Immunother Cancer. 2020;8(2):e000973.
Daisley BA, Chanyi RM, Abdur-Rashid K, Al KF, Gibbons S, Chmiel JA, et al. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients. Nat Commun. 2020;11(1):4822.
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–7.
Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97–103.
Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104–8.
Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y, Frenkel EP, et al. Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients. Neoplasia N Y N. 2017;19(10):848–55.
Xu R, Zhang Y, Chen S, Zeng Y, Fu X, Chen T, et al. The role of the probiotic Akkermansia muciniphila in brain functions: insights underpinning therapeutic potential. Crit Rev Microbiol. 2023;49(2):151–76.
Liu L, Wang H, Chen X, Zhang Y, Zhang H, Xie P. Gut microbiota and its metabolites in depression: from pathogenesis to treatment. eBioMedicine. 2023;90:104527.
Joseph J, Depp C, Shih PAB, Cadenhead KS, Schmid-Schönbein G. Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia? Front Neurosci. 2017;11:155.
Doifode T, Giridharan VV, Generoso JS, Bhatti G, Collodel A, Schulz PE, et al. The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology. Pharmacol Res. 2021;164:105314.
Dooling SW, Costa-Mattioli M. Gut Bacteria Seize Control of the Brain to Prevent Epilepsy. Cell Host Microbe. 2018;24(1):3–5.
Ding Y, Bu F, Chen T, Shi G, Yuan X, Feng Z, et al. A next-generation probiotic: Akkermansia muciniphila ameliorates chronic stress-induced depressive-like behavior in mice by regulating gut microbiota and metabolites. Appl Microbiol Biotechnol. 2021;105(21–22):8411–26.
Benevides L, Burman S, Martin R, Robert V, Thomas M, Miquel S, et al. New Insights into the Diversity of the Genus Faecalibacterium. Front Microbiol. 2017;8:1790.
Khan MT, Duncan SH, Stams AJM, van Dijl JM, Flint HJ, Harmsen HJM. The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic–anoxic interphases. ISME J. 2012;6(8):1578–85.
Rajilić-Stojanović M, Biagi E, Heilig HGHJ, Kajander K, Kekkonen RA, Tims S, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology. 2011;141(5):1792–801.
Miquel S, Martín R, Rossi O, Bermúdez-Humarán LG, Chatel JM, Sokol H, et al. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. 2013;16(3):255–61.
Cao Y, Shen J, Ran ZH. Association between Faecalibacterium prausnitzii Reduction and Inflammatory Bowel Disease: A Meta-Analysis and Systematic Review of the Literature. Gastroenterol Res Pract. 2014;2014:872725.
Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux JJ, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008;105(43):16731–6.
Lopez-Siles M, Duncan SH, Garcia-Gil LJ, Martinez-Medina M. Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics. ISME J. 2017;11(4):841–52.
Leylabadlo HE, Ghotaslou R, Feizabadi MM, Farajnia S, Moaddab SY, Ganbarov K, et al. The critical role of Faecalibacterium prausnitzii in human health: An overview. Microb Pathog. 2020;149:104344.
van Tongeren SP, Slaets JPJ, Harmsen HJM, Welling GW. Fecal microbiota composition and frailty. Appl Environ Microbiol. 2005;71(10):6438–42.
Duncan SH, Hold GL, Harmsen HJM, Stewart CS, Flint HJ. Growth requirements and fermentation products of Fusobacterium prausnitzii, and a proposal to reclassify it as Faecalibacterium prausnitzii gen. nov., comb. nov. Int J Syst Evol Microbiol. 2002;52(Pt 6):2141–6.
Ramirez-Farias C, Slezak K, Fuller Z, Duncan A, Holtrop G, Louis P. Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii. Br J Nutr. 2009;101(4):541–50.
Lopez-Siles M, Khan TM, Duncan SH, Harmsen HJM, Garcia-Gil LJ, Flint HJ. Cultured representatives of two major phylogroups of human colonic Faecalibacterium prausnitzii can utilize pectin, uronic acids, and host-derived substrates for growth. Appl Environ Microbiol. 2012;78(2):420–8.
Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol. 2000;66(4):1654–61.
Elce A, Amato F, Zarrilli F, Calignano A, Troncone R, Castaldo G, et al. Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells. Benef Microbes. 2017;8(5):841–7.
Xu J, Liang R, Zhang W, Tian K, Li J, Chen X, et al. Faecalibacterium prausnitzii-derived microbial anti-inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression. J Diabetes. 2020;12(3):224–36.
Martín R, Bermúdez-Humarán LG, Langella P. Searching for the Bacterial Effector: The Example of the Multi-Skilled Commensal Bacterium Faecalibacterium prausnitzii. Front Microbiol. 2018;9:346.
Quévrain E, Maubert MA, Michon C, Chain F, Marquant R, Tailhades J, et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut. 2016;65(3):415–25.
Wrzosek L, Miquel S, Noordine ML, Bouet S, Joncquel Chevalier-Curt M, Robert V, et al. Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii influence the production of mucus glycans and the development of goblet cells in the colonic epithelium of a gnotobiotic model rodent. BMC Biol. 2013;11:61.
Xuan W, Ou Y, Chen W, Huang L, Wen C, Huang G, et al. Faecalibacterium prausnitzii Improves Lipid Metabolism Disorder and Insulin Resistance in Type 2 Diabetic Mice. Br J Biomed Sci. 2023;80:10794.
Hao Z, Wang W, Guo R, Liu H. Faecalibacterium prausnitzii (ATCC 27766) has preventive and therapeutic effects on chronic unpredictable mild stress-induced depression-like and anxiety-like behavior in rats. Psychoneuroendocrinology. 2019;104:132–42.
Ueda A, Shinkai S, Shiroma H, Taniguchi Y, Tsuchida S, Kariya T, et al. Identification of Faecalibacterium prausnitzii strains for gut microbiome-based intervention in Alzheimer’s-type dementia. Cell Rep Med. 2021;2(9):100398.
Sun F, Zhang Q, Zhao J, Zhang H, Zhai Q, Chen W. A potential species of next-generation probiotics? The dark and light sides of Bacteroides fragilis in health. Food Res Int Ott Ont. 2019;126:108590.
Wexler AG, Goodman AL. An insider’s perspective: Bacteroides as a window into the microbiome. Nat Microbiol. 2017;2:17026.
Alexiou K, Drikos I, Terzopoulou M, Sikalias N, Ioannidis A, Economou N. A prospective randomised trial of isolated pathogens of surgical site infections (SSI). Ann Med Surg. 2012. 2017;21:25–9.
Brook I. Anaerobic pulmonary infections in children. Pediatr Emerg Care. 2004;20(9):636–40.
Chen CY, Lin MJ, Yang WC, Chang YJ, Gao FX, Wu HP. Clinical spectrum of intra-abdominal abscesses in children admitted to the pediatric emergency department. J Microbiol Immunol Infect Wei Mian Yu Gan Ran Za Zhi. 2020;53(2):283–91.
Kierzkowska M, Pedzisz P, Babiak I, Janowicz J, Kulig M, Majewska A, et al. Orthopedic infections caused by obligatory anaerobic Gram-negative rods: report of two cases. Med Microbiol Immunol (Berl). 2017;206(5):363–6.
Ou YC, Lan KC, Lin H, Tsai CC, ChangChien CC. Clinical characteristics of perforated pyometra and impending perforation: specific issues in gynecological emergency. J Obstet Gynaecol Res. 2010;36(3):661–6.
Singh S, Goyal V, Padhi P, Aoun E. Bacteroides fragilis endocarditis in a patient with Crohn’s disease. BMJ Case Rep. 2013;2013:bcr2013009248.
Zhao Y, Jaber V, Lukiw WJ. Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer’s Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus. Front Cell Infect Microbiol. 2017;7:318.
Bjerke GA, Wilson R, Storrø O, Øyen T, Johnsen R, Rudi K. Mother-to-child transmission of and multiple-strain colonization by Bacteroides fragilis in a cohort of mothers and their children. Appl Environ Microbiol. 2011;77(23):8318–24.
Border M, Firehammer BD, Shoop DS, Myers LL. Isolation of Bacteroides fragilis from the feces of diarrheic calves and lambs. J Clin Microbiol. 1985;21(3):472–3.
Collins JE, Bergeland ME, Myers LL, Shoop DS. Exfoliating colitis associated with enterotoxigenic Bacteroides fragilis in a piglet. J Vet Diagn Investig Off Publ Am Assoc Vet Lab Diagn Inc. 1989;1(4):349–51.
Myers LL, Shoop DS, Collins JE, Bradbury WC. Diarrheal disease caused by enterotoxigenic Bacteroides fragilis in infant rabbits. J Clin Microbiol. 1989;27(9):2025–30.
Spence C, Wells WG, Smith CJ. Characterization of the primary starch utilization operon in the obligate anaerobe Bacteroides fragilis: Regulation by carbon source and oxygen. J Bacteriol. 2006;188(13):4663–72.
Li J, Xu H, Sun Z, Hou Q, Kwok LY, Laga W, et al. Effect of dietary interventions on the intestinal microbiota of Mongolian hosts. Sci Bull. 2016;61(20):1605–14.
La-ongkham O, Nakphaichit M, Leelavatcharamas V, Keawsompong S, Nitisinprasert S. Distinct gut microbiota of healthy children from two different geographic regions of Thailand. Arch Microbiol. 2015;197(4):561–73.
Talsness CE, Penders J, Jansen EHJM, Damoiseaux J, Thijs C, Mommers M. Influence of vitamin D on key bacterial taxa in infant microbiota in the KOALA Birth Cohort Study. PLOS ONE. 2017;12(11):e0188011.
Nagata S, Chiba Y, Wang C, Yamashiro Y. The effects of the Lactobacillus casei strain on obesity in children: a pilot study. Benef Microbes. 2017;8(4):535–43.
Asama T, Kimura Y, Kono T, Tatefuji T, Hashimoto K, Benno Y. Effects of heat-killed Lactobacillus kunkeei YB38 on human intestinal environment and bowel movement: a pilot study. Benef Microbes. 2016;7(3):337–44.
Franco AA, Cheng RK, Chung GT, Wu S, Oh HB, Sears CL. Molecular evolution of the pathogenicity island of enterotoxigenic Bacteroides fragilis strains. J Bacteriol. 1999;181(21):6623–33.
Nikitina AS, Kharlampieva DD, Babenko VV, Shirokov DA, Vakhitova MT, Manolov AI, et al. Complete Genome Sequence of an Enterotoxigenic Bacteroides fragilis Clinical Isolate. Genome Announc. 2015;3(3):e00450-15.
Wagner VE, Dey N, Guruge J, Hsiao A, Ahern PP, Semenkovich NP, et al. Effects of a gut pathobiont in a gnotobiotic mouse model of childhood undernutrition. Sci Transl Med. 2016;8(366):366ra164.
Young NM, Kreisman LSC, Stupak J, MacLean LL, Cobb BA, Richards JC. Structural characterization and MHCII-dependent immunological properties of the zwitterionic O-chain antigen of Morganella morganii. Glycobiology. 2011;21(10):1266–76.
Velez CD, Lewis CJ, Kasper DL, Cobb BA. Type I Streptococcus pneumoniae carbohydrate utilizes a nitric oxide and MHC II-dependent pathway for antigen presentation. Immunology. 2009;127(1):73–82.
Mashburn-Warren L, McLean RJC, Whiteley M. Gram-negative outer membrane vesicles: beyond the cell surface. Geobiology. 2008;6(3):214–9.
Krinos CM, Coyne MJ, Weinacht KG, Tzianabos AO, Kasper DL, Comstock LE. Extensive surface diversity of a commensal microorganism by multiple DNA inversions. Nature. 2001;414(6863):555–8.
Liu CH, Lee SM, Vanlare JM, Kasper DL, Mazmanian SK. Regulation of surface architecture by symbiotic bacteria mediates host colonization. Proc Natl Acad Sci U S A. 2008;105(10):3951–6.
Coyne MJ, Reinap B, Lee MM, Comstock LE. Human symbionts use a host-like pathway for surface fucosylation. Science. 2005;307(5716):1778–81.
Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155(7):1451–63.
Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008;453(7195):620–5.
Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A. 2010;107(27):12204–9.
Ochoa-Repáraz J, Mielcarz DW, Ditrio LE, Burroughs AR, Begum-Haque S, Dasgupta S, et al. Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J Immunol. 2010;185(7):4101–8.
Lee YK, Mehrabian P, Boyajian S, Wu WL, Selicha J, Vonderfecht S, et al. The Protective Role of Bacteroides fragilis in a Murine Model of Colitis-Associated Colorectal Cancer. mSphere. 2018;3(6):e00587-18.
Johnson JL, Jones MB, Cobb BA. Polysaccharide-experienced effector T cells induce IL-10 in FoxP3+ regulatory T cells to prevent pulmonary inflammation. Glycobiology. 2018;28(1):50–8.
Johnson JL, Jones MB, Cobb BA. Bacterial capsular polysaccharide prevents the onset of asthma through T-cell activation. Glycobiology. 2015;25(4):368–75.
Sofi MH, Wu Y, Ticer T, Schutt S, Bastian D, Choi HJ, et al. A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD. JCI Insight. 2021;6(3):e136841.
Erturk-Hasdemir D, Ochoa-Repáraz J, Kasper DL, Kasper LH. Exploring the Gut-Brain Axis for the Control of CNS Inflammatory Demyelination: Immunomodulation by Bacteroides fragilis’ Polysaccharide A. Front Immunol. 2021;12:662807.
Ramakrishna C, Kujawski M. Chu H. et al. Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis. Nat Commun. 2019;10:2153.
Ochoa-Repáraz J, Mielcarz DW. Ditrio LE, Burroughs AR, Begum-Haque S, Dasgupta S, Kasper DL, Kasper LH. Central Nervous System Demyelinating Disease Protection by the Human Commensal Bacteroides fragilis Depends on Polysaccharide A Expression. J Immunol. 2010;185 (7):4101–4108.
Wang Y, Deng H, Li Z, Tan Y, Han Y, Wang X, et al. Safety Evaluation of a Novel Strain of Bacteroides fragilis. Front Microbiol. 2017;8:435.
