Compendium of Bifidobacterium-based probiotics: characteristics and therapeutic impact on human diseases

Abstract

The human microbiota, a complex community of microorganisms residing in and on the human body, plays a crucial role in maintaining health and preventing disease. Bifidobacterium species have shown remarkable therapeutic potential across a range of health conditions, thus being considered optimal probiotic bacteria. This review provides insights into the concept of probiotics and explores the impact of bifidobacteria on human health, focusing on the gastrointestinal, respiratory, skeletal, muscular, and nervous systems. It also integrates information on the available genetic bases underlying the beneficial effects of each bifidobacterial probiotic species on different aspects of human physiology. Notably, Bifidobacterium-based probiotics have proven effective in managing gastrointestinal conditions such as constipation, antibiotic-associated diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Helicobacter pylori infections. These benefits are achieved by modulating the intestinal microbiota, boosting immune responses, and strengthening the gut barrier. Moreover, Bifidobacterium species have been reported to reduce respiratory infections and asthma severity. Additionally, these probiotic bacteria offer benefits for skeletal and muscular health, as evidenced by Bifidobacterium adolescentis and Bifidobacterium breve, which have shown anti-inflammatory effects and symptom relief in arthritis models, suggesting potential in treating conditions like rheumatoid arthritis. Furthermore, probiotic therapies based on bifidobacterial species have shown promising effects in alleviating anxiety and depression, reducing stress, and enhancing cognitive function. Overall, this review integrates the extensive scientific literature now available that supports the health-promoting applications of probiotic Bifidobacterium species and underscores the need for further research to confirm their clinical efficacy across different body systems.

Keywords

Microbiota / microbiome / probiotic / beneficial bacteria / bifidobacteria / Bifidobacterium

References

[1] Fan Y.Gut microbiota in human metabolic health and disease.Nat Rev Microbiol2021;19:55-71

[2] Lynch SV.The human intestinal microbiome in health and disease.N Engl J Med2016;375:2369-79

[3] Candela M,Carnevali P.Interaction of probiotic Lactobacillus and Bifidobacterium strains with human intestinal epithelial cells: adhesion properties, competition against enteropathogens and modulation of IL-8 production.Int J Food Microbiol2008;125:286-92

[4] Olszak T,Zeissig S.Microbial exposure during early life has persistent effects on natural killer T cell function.Science2012;336:489-93 PMCID:PMC3437652

[5] Fukuda S,Hase K.Bifidobacteria can protect from enteropathogenic infection through production of acetate.Nature2011;469:543-7

[6] Cullin N,Straussman R,Elinav E.Microbiome and cancer.Cancer Cell2021;39:1317-41

[7] Reynoso-García J,Meléndez-Vázquez NM.A complete guide to human microbiomes: body niches, transmission, development, dysbiosis, and restoration.Front Syst Biol2022;2:951403 PMCID:PMC11238057

[8] Li N,Huang S.Spatial heterogeneity of bacterial colonization across different gut segments following inter-species microbiota transplantation.Microbiome2020;8:161 PMCID:PMC7677849

[9] Gomaa EZ.Human gut microbiota/microbiome in health and diseases: a review.Antonie Van Leeuwenhoek2020;113:2019-40

[10] Carding S,Vipond DT,Owen LJ.Dysbiosis of the gut microbiota in disease.Microb Ecol Health Dis2015;26:26191 PMCID:PMC4315779

[11] Milani C,Bottacini F.The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota.Microbiol Mol Biol Rev2017;81:e00036-17 PMCID:PMC5706746

[12] Fassarella M,Penders J,Smidt H.Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health.Gut2021;70:595-605

[13] Mancabelli L,Fontana F.A pilot study to disentangle the infant gut microbiota composition and identification of bacteria correlates with high fat mass.Microbiome Res Rep2023;2:23 PMCID:PMC10688801

[14] Requena T.The human microbiome in sickness and in health.Rev Clin Esp2021;221:233-40

[15] Thursby E.Introduction to the human gut microbiota.Biochem J2017;474:1823-36 PMCID:PMC5433529

[16] Baumgart DC.Inflammatory bowel disease: cause and immunobiology.Lancet2007;369:1627-40

[17] De Palma G,Medina M.Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children.BMC Microbiol2010;10:63 PMCID:PMC2843610

[18] Guinane CM.Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ.Therap Adv Gastroenterol2013;6:295-308 PMCID:PMC3667473

[19] Perler BK,Wu GD.The role of the gut microbiota in the relationship between diet and human health.Annu Rev Physiol2023;85:449-68

[20] Yadav MK,Singh B,Tiwari SK.Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics.Appl Microbiol Biotechnol2022;106:505-21 PMCID:PMC8749913

[21] Gibson GR.Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics.J Nutr1995;125:1401-12

[22] Bakker GJ.Fecal microbiota transplantation: therapeutic potential for a multitude of diseases beyond clostridium difficile.Microbiol Spectr2017;5:291-308

[23] Evrensel A.Fecal microbiota transplantation and its usage in neuropsychiatric disorders.Clin Psychopharmacol Neurosci2016;14:231-7 PMCID:PMC4977816

[24] Ramai D,Ofosu A,Reddy M.Fecal microbiota transplantation: donor relation, fresh or frozen, delivery methods, cost-effectiveness.Ann Gastroenterol2019;32:30-8 PMCID:PMC6302197

[25] Rossen NG,de Vries EM.Fecal microbiota transplantation as novel therapy in gastroenterology: a systematic review.World J Gastroenterol2015;21:5359-71 PMCID:PMC4419078

[26] Vendrik KEW,de Jong PRC.Fecal microbiota transplantation in neurological disorders.Front Cell Infect Microbiol2020;10:98 PMCID:PMC7105733

[27] Xu HM,Zhou YL.Fecal microbiota transplantation: a new therapeutic attempt from the gut to the brain.Gastroenterol Res Pract2021;2021:6699268 PMCID:PMC7826222

[28] Biazzo M.Fecal microbiota transplantation as new therapeutic avenue for human diseases.J Clin Med2022;11:4119 PMCID:PMC9320118

[29] Ooijevaar RE,Verspaget HW,Keller JJ.Clinical application and potential of fecal microbiota transplantation.Annu Rev Med2019;70:335-51

[30] Wang JW,Kuo FC.Fecal microbiota transplantation: review and update.J Formos Med Assoc2019;118:S23-31

[31] Butel MJ.Probiotics, gut microbiota and health.Med Mal Infect2014;44:1-8

[32] Linares DM,Renes E.Lactic acid bacteria and bifidobacteria with potential to design natural biofunctional health-promoting dairy foods.Front Microbiol2017;8:846 PMCID:PMC5435742

[33] Piqué N,Miñana-Galbis D.Health benefits of heat-killed (tyndallized) probiotics: an overview.Int J Mol Sci2019;20:2534 PMCID:PMC6566317

[34] Dominguez-Bello MG,Contreras M.Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.Proc Natl Acad Sci U S A2010;107:11971-5 PMCID:PMC2900693

[35] Cukrowska B,Zakrzewska M,Maciorkowska E.The relationship between the infant gut microbiota and allergy. The role of Bifidobacterium breve and prebiotic oligosaccharides in the activation of anti-allergic mechanisms in early life.Nutrients2020;12:946 PMCID:PMC7230322

[36] Turroni F,Bottacini F,Van Sinderen D.Bifidobacterium bifidum as an example of a specialized human gut commensal.Front Microbiol2014;5:437 PMCID:PMC4140077

[37] Gutierrez A,Engevik MA.Bifidobacterium and the intestinal mucus layer.Microbiome Res Rep2023;2:36 PMCID:PMC10688832

[38] Ruas-Madiedo P,Fernández-García M,Margolles A.Mucin degradation by Bifidobacterium strains isolated from the human intestinal microbiota.Appl Environ Microbiol2008;74:1936-40 PMCID:PMC2268317

[39] Gavzy SJ,Lee ZL,Ma B.Bifidobacterium mechanisms of immune modulation and tolerance.Gut Microbes2023;15:2291164 PMCID:PMC10730214

[40] Milani C,Lugli GA.Exploring vertical transmission of bifidobacteria from mother to child.Appl Environ Microbiol2015;81:7078-87 PMCID:PMC4579462

[41] Favier C,Mizon C,Colombel JF.Fecal beta-D-galactosidase production and Bifidobacteria are decreased in Crohn’s disease.Dig Dis Sci1997;42:817-22

[42] Macfarlane S,Cummings JH.Chemotaxonomic analysis of bacterial populations colonizing the rectal mucosa in patients with ulcerative colitis.Clin Infect Dis2004;38:1690-9

[43] Mylonaki M,Rampton DS,Brostoff J.Molecular characterization of rectal mucosa-associated bacterial flora in inflammatory bowel disease.Inflamm Bowel Dis2005;11:481-7

[44] Gueimonde M,Huhtinen H,Salminen S.Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease.World J Gastroenterol2007;13:3985-9 PMCID:PMC4171173

[45] Martin AJM,Riquelme E,Garrido D.Microbial interactions and the homeostasis of the gut microbiome: the role of Bifidobacterium.Microbiome Res Rep2023;2:17 PMCID:PMC10688804

[46] Kiseleva EP,Sviridov OV,Knirel YA.The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases.Benef Microbes2011;2:139-54

[47] Benvenga S.Molecular mimicry and autoimmune thyroid disease.Rev Endocr Metab Disord2016;17:485-98

[48] López P,Sánchez B.Interaction of Bifidobacterium bifidum LMG13195 with HT29 cells influences regulatory-T-cell-associated chemokine receptor expression.Appl Environ Microbiol2012;78:2850-7 PMCID:PMC3318848

[49] Agrawal A,Morris J.Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation.Aliment Pharmacol Ther2009;29:104-14

[50] Guyonnet D,Ducrotte P.Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial.Aliment Pharmacol Ther2007;26:475-86

[51] Hidalgo-Cantabrana C,Ruiz L,Sánchez B.Bifidobacteria and their health-promoting effects.Microbiol Spectr2017;5:73-98

[52] Muñoz JA,Casinos B.Novel probiotic Bifidobacterium longum subsp. infantis CECT 7210 strain active against rotavirus infections.Appl Environ Microbiol2011;77:8775-83 PMCID:PMC3233071

[53] Hill C,Reid G.Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.Nat Rev Gastroenterol Hepatol2014;11:506-14

[54] Gibson GR,Sanders ME.Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics.Nat Rev Gastroenterol Hepatol2017;14:491-502

[55] Rahman MN,Tin MCF,Wong SH.The use of probiotics and prebiotics in decolonizing pathogenic bacteria from the gut; a systematic review and meta-analysis of clinical outcomes.Gut Microbes2024;16:2356279 PMCID:PMC11123511

[56] Li C,Xiao S,Yu Q.The role of Lactobacillus in inflammatory bowel disease: from actualities to prospects.Cell Death Discov2023;9:361 PMCID:PMC10541886

[57] Mousa WK,Ghemrawi R.Probiotics modulate host immune response and interact with the gut microbiota: shaping their composition and mediating antibiotic resistance.Int J Mol Sci2023;24:13783 PMCID:PMC10531388

[58] Liu Y,Wu C.Modulation of gut microbiota and immune system by probiotics, pre-biotics, and post-biotics.Front Nutr2021;8:634897 PMCID:PMC8761849

[59] Hemarajata P.Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation.Therap Adv Gastroenterol2013;6:39-51 PMCID:PMC3539293

[60] Petrariu OA,Niculescu AG.Role of probiotics in managing various human diseases, from oral pathology to cancer and gastrointestinal diseases.Front Microbiol2023;14:1296447 PMCID:PMC10797027

[61] Galdeano C, Cazorla SI, Lemme Dumit JM, Vélez E, Perdigón G. Beneficial effects of probiotic consumption on the immune system.Ann Nutr Metab2019;74:115-24

[62] Majeed M,Arumugam S,Ali F.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.Food Nutr Res2018;62: PMCID:PMC6034030

[63] Nataraj BH,Behare PV.Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods.Microb Cell Fact2020;19:168 PMCID:PMC7441679

[64] Martyniak A,Wędrychowicz A,Tomasik PJ.Prebiotics, probiotics, synbiotics, paraprobiotics and postbiotic compounds in IBD.Biomolecules2021;11:1903 PMCID:PMC8699341

[65] Ford AC,Lacy BE.Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis.Am J Gastroenterol2014;109:1547-61

[66] Li B,Deng H,Shu H.Efficacy and safety of probiotics in irritable bowel syndrome: a systematic review and meta-analysis.Front Pharmacol2020;11:332 PMCID:PMC7147251

[67] Goodman C,Georgousopoulou E,Levett K.Probiotics for the prevention of antibiotic-associated diarrhoea: a systematic review and meta-analysis.BMJ Open2021;11:e043054 PMCID:PMC8362734

[68] Mazziotta C,Martini F,Rotondo JC.Probiotics mechanism of action on immune cells and beneficial effects on human health.Cells2023;12:184 PMCID:PMC9818925

[69] Kopacz K.Probiotics for the prevention of antibiotic-associated diarrhea.Healthcare2022;10:1450 PMCID:PMC9408191

[70] Cremon C,Ventura M.Pre- and probiotic overview.Curr Opin Pharmacol2018;43:87-92

[71] Roy S.Role of prebiotics, probiotics, and synbiotics in management of inflammatory bowel disease: current perspectives.World J Gastroenterol2023;29:2078-100 PMCID:PMC10130969

[72] Suez J,Segal E.The pros, cons, and many unknowns of probiotics.Nat Med2019;25:716-29

[73] Evivie SE,Igene JO.Some current applications, limitations and future perspectives of lactic acid bacteria as probiotics.Food Nutr Res2017;61:1318034 PMCID:PMC5475324

[74] Anadón A,Aranzazu Martínez M.Probiotics for animal nutrition in the European Union. Regulation and safety assessment.Regul Toxicol Pharmacol2006;45:91-5

[75] Gaggìa F,Biavati B.Probiotics and prebiotics in animal feeding for safe food production.Int J Food Microbiol2010;141:S15-28

[76] Markowiak P.Effects of probiotics, prebiotics, and synbiotics on human health.Nutrients2017;9:1021 PMCID:PMC5622781

[77] Azad MAK,Li T.Probiotic species in the modulation of gut microbiota: an overview.Biomed Res Int2018;2018:9478630 PMCID:PMC5964481

[78] Holzapfel WH,Geisen R,Schillinger U.Taxonomy and important features of probiotic microorganisms in food and nutrition.Am J Clin Nutr2001;73:365S-73S

[79] Kechagia M,Konstantopoulou S.Health benefits of probiotics: a review.ISRN Nutr2013;2013:481651 PMCID:PMC4045285

[80] Salminen S,Endo A.The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics.Nat Rev Gastroenterol Hepatol2021;18:649-67 PMCID:PMC8387231

[81] Cuevas-González PF,Aguilar-Toalá JE.Postbiotics and paraprobiotics: from concepts to applications.Food Res Int2020;136:109502

[82] Hosseini SH,Moradi M.Beyond probiotics: exploring the potential of postbiotics and parabiotics in veterinary medicine.Res Vet Sci2024;167:105133

[83] Chen J,Ho CL.Recent development of probiotic bifidobacteria for treating human diseases.Front Bioeng Biotechnol2021;9:770248 PMCID:PMC8727868

[84] Jäger R,Carpenter KC.International society of sports nutrition position stand: probiotics.J Int Soc Sports Nutr2019;16:62 PMCID:PMC6925426

[85] Browne HP,Lawley TD.Mother-infant transmission of human microbiota.Curr Opin Microbiol2022;69:102173

[86] Vatanen T,Schwager R.The human gut microbiome in early-onset type 1 diabetes from the TEDDY study.Nature2018;562:589-94 PMCID:PMC6296767

[87] Lawson MAE,Kujawska M.Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem.ISME J2020;14:635-48 PMCID:PMC6976680

[88] Sakanaka M,Gotoh A.Evolutionary adaptation in fucosyllactose uptake systems supports bifidobacteria-infant symbiosis.Sci Adv2019;5:eaaw7696 PMCID:PMC6713505

[89] Schöpping M,Neves AR,Zeidan AA.Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling.NPJ Syst Biol Appl2021;7:47 PMCID:PMC8660834

[90] Alessandri G,Ventura M.The genus Bifidobacterium: from genomics to functionality of an important component of the mammalian gut microbiota running title: Bifidobacterial adaptation to and interaction with the host.Comput Struct Biotechnol J2021;19:1472-87 PMCID:PMC7979991

[91] Tarracchini C,Mancabelli L.Exploring the vitamin biosynthesis landscape of the human gut microbiota.mSystems2024;e0092924

[92] Alessandri G,MacSharry J,Ventura M.Bifidobacterial dialogue with its human host and consequent modulation of the immune system.Front Immunol2019;10:2348 PMCID:PMC6779802

[93] Rivière A,Lantin D,De Vuyst L.Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut.Front Microbiol2016;7:979 PMCID:PMC4923077

[94] Duranti S,Lugli GA.Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA.Sci Rep2020;10:14112 PMCID:PMC7445748

[95] Tojo R,Clemente MG.Intestinal microbiota in health and disease: role of bifidobacteria in gut homeostasis.World J Gastroenterol2014;20:15163-76 PMCID:PMC4223251

[96] Forootan M,Darvishi M.Chronic constipation: a review of literature.Medicine2018;97:e10631 PMCID:PMC5976340

[97] Wang L,Tian P.A randomised, double-blind, placebo-controlled trial of Bifidobacterium bifidum CCFM16 for manipulation of the gut microbiota and relief from chronic constipation.Food Funct2022;13:1628-40

[98] Fuyuki A,Kessoku T.Efficacy of Bifidobacterium bifidum G9-1 in improving quality of life in patients with chronic constipation: a prospective intervention study.Biosci Microbiota Food Health2021;40:105-14 PMCID:PMC8099630

[99] Makizaki Y,Yokota H,Tanaka Y.Improvement of loperamide-induced slow transit constipation by Bifidobacterium bifidum G9-1 is mediated by the correction of butyrate production and neurotransmitter profile due to improvement in dysbiosis.PLoS One2021;16:e0248584 PMCID:PMC7984621

[100] Nakamura Y,Murakami S.Integrated gut microbiome and metabolome analyses identified fecal biomarkers for bowel movement regulation by Bifidobacterium longum BB536 supplementation: A RCT.Comput Struct Biotechnol J2022;20:5847-58 PMCID:PMC9636538

[101] Wang L,Xu Q.Bifidobacteria exert species-specific effects on constipation in BALB/c mice.Food Funct2017;8:3587-600

[102] Wang L,Wang J.Bifidobacterium longum relieves constipation by regulating the intestinal barrier of mice.Food Funct2022;13:5037-49

[103] Becattini S,Pamer EG.Antibiotic-induced changes in the intestinal microbiota and disease.Trends Mol Med2016;22:458-78 PMCID:PMC4885777

[104] Patangia DV,Dempsey E,Stanton C.Impact of antibiotics on the human microbiome and consequences for host health.Microbiologyopen2022;11:e1260 PMCID:PMC8756738

[105] Willing BP,Finlay BB.Shifting the balance: antibiotic effects on host-microbiota mutualism.Nat Rev Microbiol2011;9:233-43

[106] Dahiya D.Antibiotic-therapy-induced gut dysbiosis affecting gut microbiota-brain axis and cognition: restoration by intake of probiotics and synbiotics.Int J Mol Sci2023;24:3074 PMCID:PMC9959899

[107] Dahiya D.The gut microbiota influenced by the intake of probiotics and functional foods with prebiotics can sustain wellness and alleviate certain ailments like gut-inflammation and colon-cancer.Microorganisms2022;10:665 PMCID:PMC8954736

[108] Duvallet C,Gurry T,Alm EJ.Meta-analysis of gut microbiome studies identifies disease-specific and shared responses.Nat Commun2017;8:1784 PMCID:PMC5716994

[109] Wirbel J,Kartal E.Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer.Nat Med2019;25:679-89 PMCID:PMC7984229

[110] Feng C,Zhang T.Heat-killed Bifidobacterium bifidum B1628 May alleviate dextran sulfate sodium-induced colitis in mice, and the anti-inflammatory effect is associated with gut microbiota modulation.Nutrients2022;14:5233 PMCID:PMC9784753

[111] Makizaki Y,Oikawa Y.Probiotic Bifidobacterium bifidum G9-1 ameliorates phytohemagglutinin-induced diarrhea caused by intestinal dysbiosis.Microbiol Immunol2019;63:481-6

[112] Kawahara T,Oikawa Y.Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.PLoS One2017;12:e0173979 PMCID:PMC5367788

[113] Okai S,Ohta M.Intestinal IgA as a modulator of the gut microbiota.Gut Microbes2017;8:486-92 PMCID:PMC5628655

[114] Michels M,Cucker L.Bifidobacterium lactis CCT 7858 improves gastrointestinal symptoms by antibiotics treatment: a double-blind, randomized, placebo-controlled trial.Probiotics Antimicrob Proteins2023;15:738-48

[115] Merenstein D,Roberts RF.Bifidobacterium animalis subsp. lactis BB-12 protects against antibiotic-induced functional and compositional changes in human fecal microbiome.Nutrients2021;13:2814 PMCID:PMC8398419

[116] Xu B,Zhao J.Bifidobacterium animalis subsp. lactis XLTG11 improves antibiotic-related diarrhea by alleviating inflammation, enhancing intestinal barrier function and regulating intestinal flora.Food Funct2022;13:6404-18

[117] Guarino A,Berkley J.Acute gastroenteritis in children of the world: what needs to be done?.J Pediatr Gastroenterol Nutr2020;70:694-701 PMCID:PMC7613312

[118] Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD; WHO-coordinated Global Rotavirus Surveillance Network. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis.Lancet Infect Dis2012;12:136-41

[119] Patel MM,Glass RI,Vinjé J.Systematic literature review of role of noroviruses in sporadic gastroenteritis.Emerg Infect Dis2008;14:1224-31 PMCID:PMC2600393

[120] Rackoff LA,Green KY.Epidemiology and evolution of rotaviruses and noroviruses from an archival WHO Global Study in Children (1976-79) with implications for vaccine design.PLoS One2013;8:e59394 PMCID:PMC3607611

[121] Walker CLF,Liu L.Global burden of childhood pneumonia and diarrhoea.Lancet2013;381:1405-16 PMCID:PMC7159282

[122] Lanata CF, Fischer-Walker CL, Olascoaga AC, Torres CX, Aryee MJ, Black RE; Child Health Epidemiology Reference Group of the World Health Organization and UNICEF. Global causes of diarrheal disease mortality in children <5 years of age: a systematic review.PLoS One2013;8:e72788 PMCID:PMC3762858

[123] Nirwati H,Mawarti Y.Norovirus and rotavirus infections in children less than five years of age hospitalized with acute gastroenteritis in Indonesia.Arch Virol2019;164:1515-25

[124] Galán NN, Ulloa Rubiano JC, Velez Reyes FA, Fernandez Duarte KP, Salas Cárdenas SP, Gutierrez Fernandez MF. In vitro antiviral activity of Lactobacillus casei and Bifidobacterium adolescentis against rotavirus infection monitored by NSP4 protein production.J Appl Microbiol2016;120:1041-51

[125] Gonzalez-Ochoa G,Icedo-Garcia R,Tamez-Guerra P.Modulation of rotavirus severe gastroenteritis by the combination of probiotics and prebiotics.Arch Microbiol2017;199:953-61 PMCID:PMC5548957

[126] Li D,le Pendu J.Anti-viral effect of Bifidobacterium adolescentis against noroviruses.Front Microbiol2016;7:864 PMCID:PMC4896916

[127] Fernandez-Duarte KP,Salas-Cárdenas SP,Gutierrez-Fernandez MF.Bifidobacterium adolescentis (DSM 20083) and Lactobacillus casei (Lafti L26-DSL): probiotics able to block the in vitro adherence of rotavirus in MA104 cells.Probiotics Antimicrob Proteins2018;10:56-63 PMCID:PMC5801392

[128] Wittmann A,Frick JS.Plasmacytoid dendritic cells are crucial in Bifidobacterium adolescentis-mediated inhibition of Yersinia enterocolitica infection.Plasmacytoid dendritic cells are crucial in Bifidobacterium adolescentis-mediated inhibition of Yersinia enterocolitica infection.PLoS One2013;8:e71338 PMCID:PMC3748105

[129] Kim MJ,Park JE,Seo JG.Antiviral activity of Bifidobacterium adolescentis SPM1605 against Coxsackievirus B3.Biotechnol Biotechnol Equip2014;28:681-8 PMCID:PMC4433936

[130] Shankar S.Diet and management of diarrhea.Indian J Pediatr2024;91:590-7

[131] Culpepper T,Nieves C Jr.Bifidobacterium bifidum R0071 decreases stress-associated diarrhoea-related symptoms and self-reported stress: a secondary analysis of a randomised trial.Benef Microbes2016;7:327-36

[132] Koloski NA,Kalantar J,Zaguirre J.The brain--gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study.Gut2012;61:1284-90

[133] Hughes C,Colee JC.Galactooligosaccharide supplementation reduces stress-induced gastrointestinal dysfunction and days of cold or flu: a randomized, double-blind, controlled trial in healthy university students.Am J Clin Nutr2011;93:1305-11

[134] de Roos NM, Katan MB. Effects of probiotic bacteria on diarrhea, lipid metabolism, and carcinogenesis: a review of papers published between 1988 and 1998.Am J Clin Nutr2000;71:405-11

[135] Gomi A,Shibahara-Sone H,Miyazaki K.Effect of Bifidobacterium bifidum BF-1 on gastric protection and mucin production in an acute gastric injury rat model.J Dairy Sci2013;96:832-7

[136] Urita Y,Watanabe T.Continuous consumption of fermented milk containing Bifidobacterium bifidum YIT 10347 improves gastrointestinal and psychological symptoms in patients with functional gastrointestinal disorders.Biosci Microbiota Food Health2015;34:37-44 PMCID:PMC4405396

[137] Guandalini S.Probiotics in the treatment of inflammatory bowel disease. In: Guandalini S, Indrio F, editors. Probiotics and child gastrointestinal health. Cham: Springer; 2019. pp. 101-7.

[138] O’Callaghan A.Bifidobacteria and their role as members of the human gut microbiota.Front Microbiol2016;7:925 PMCID:PMC4908950

[139] Bosselaar S,Dautel E.Taxonomic and phenotypic analysis of bifidobacteria isolated from IBD patients as potential probiotic strains.BMC Microbiol2024;24:233 PMCID:PMC11218132

[140] Duranti S,Mancabelli L.Elucidating the gut microbiome of ulcerative colitis: bifidobacteria as novel microbial biomarkers.FEMS Microbiol Ecol2016;92:fiw191

[141] Vavricka SR,Scharl M,Navarini A.Extraintestinal manifestations of inflammatory bowel disease.Inflamm Bowel Dis2015;21:1982-92 PMCID:PMC4511685

[142] Peng C,Miao Z.Early life administration of Bifidobacterium bifidum BD-1 alleviates long-term colitis by remodeling the gut microbiota and promoting intestinal barrier development.Front Microbiol2022;13:916824 PMCID:PMC9355606

[143] Ishikawa H,Ohashi Y.Beneficial effects of probiotic Bifidobacterium and galacto-oligosaccharide in patients with ulcerative colitis: a randomized controlled study.Digestion2011;84:128-33

[144] Guglielmetti S,Gschwender M.Randomised clinical trial: Bifidobacterium bifidum MIMBb75 significantly alleviates irritable bowel syndrome and improves quality of life--a double-blind, placebo-controlled study.Aliment Pharmacol Ther2011;33:1123-32

[145] Tomita T,Okugawa T.Effect of Bifidobacterium bifidum G9-1 on the intestinal environment and diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms in patients with quiescent Crohn’s disease: a prospective pilot study.J Clin Med2023;12:3368 PMCID:PMC10219535

[146] Andresen V,Layer P.Heat-inactivated Bifidobacterium bifidum MIMBb75 (SYN-HI-001) in the treatment of irritable bowel syndrome: a multicentre, randomised, double-blind, placebo-controlled clinical trial.Lancet Gastroenterol Hepatol2020;5:658-66

[147] Lenoir M,Fardao-Beyler F.An 8-week course of Bifidobacterium longum 35624^® is associated with a reduction in the symptoms of irritable bowel syndrome.Probiotics Antimicrob Proteins2023;Online ahead of print:

[148] Sabaté JM.Effect of Bifidobacterium longum 35624 on disease severity and quality of life in patients with irritable bowel syndrome.World J Gastroenterol2022;28:732-44 PMCID:PMC8891724

[149] He C,Zhu Y.Probiotics modulate gastrointestinal microbiota after Helicobacter pylori eradication: A multicenter randomized double-blind placebo-controlled trial.Front Immunol2022;13:1033063 PMCID:PMC9679295

[150] Gomi A,Watanabe O.Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms in healthy adults: a double-blind, randomized, placebo-controlled study.J Dairy Sci2018;101:4830-41

[151] Cheng J.Gastroesophageal reflux disease and probiotics: a systematic review.Nutrients2020;12:132 PMCID:PMC7019778

[152] Zheng Y,Zhang T.A Bifidobacterium animalis subsp. lactis strain that can suppress Helicobacter pylori: isolation, in vitro and in vivo validation.Lett Appl Microbiol2024;77:ovae005

[153] Marteau P,Quinquis L,Whorwell PJ.Consumption of a fermented milk product containing Bifidobacterium lactis CNCM I-2494 in women complaining of minor digestive symptoms: rapid response which is independent of dietary fibre intake or physical activity.Nutrients2019;11:92 PMCID:PMC6356475

[154] Chibbar R.The gut microbiota in celiac disease and probiotics.Nutrients2019;11:2375 PMCID:PMC6836185

[155] Pecora F,Gismondi P.Gut microbiota in celiac disease: is there any role for probiotics?.Front Immunol2020;11:957 PMCID:PMC7243837

[156] Klemenak M,Langerholc T,Mičetić-Turk D.Administration of Bifidobacterium breve decreases the production of TNF-α in children with celiac disease.Dig Dis Sci2015;60:3386-92

[157] Quagliariello A,Bozzi Cionci N.Effect of Bifidobacterium breve on the intestinal microbiota of coeliac children on a gluten free diet: a pilot study.Nutrients2016;8:660 PMCID:PMC5084046

[158] Olivares M,Sanz Y.Influence of Bifidobacterium longum CECT 7347 and gliadin peptides on intestinal epithelial cell proteome.J Agric Food Chem2011;59:7666-71

[159] Medina M,Ribes-Koninckx C,Sanz Y.Bifidobacterium strains suppress in vitro the pro-inflammatory milieu triggered by the large intestinal microbiota of coeliac patients.J Inflamm2008;5:19 PMCID:PMC2640389

[160] Laparra JM,Gallina O.Bifidobacterium longum CECT 7347 modulates immune responses in a gliadin-induced enteropathy animal model.PLoS One2012;7:e30744 PMCID:PMC3277586

[161] Guardamagna O,Puddu PE.Bifidobacteria supplementation: effects on plasma lipid profiles in dyslipidemic children.Nutrition2014;30:831-6

[162] Bordoni A,Leonardi A.Cholesterol-lowering probiotics: in vitro selection and in vivo testing of bifidobacteria.Appl Microbiol Biotechnol2013;97:8273-81

[163] Zanotti I,Piemontese A.Evidence for cholesterol-lowering activity by Bifidobacterium bifidum PRL2010 through gut microbiota modulation.Appl Microbiol Biotechnol2015;99:6813-29

[164] Minami JI,Yanagisawa N.Oral administration of Bifidobacterium breve B-3 modifies metabolic functions in adults with obese tendencies in a randomised controlled trial.J Nutr Sci2015;4:e17 PMCID:PMC4463018

[165] Minami J,Tanaka M.Effects of Bifidobacterium breve B-3 on body fat reductions in pre-obese adults: a randomized, double-blind, placebo-controlled trial.Biosci Microbiota Food Health2018;37:67-75 PMCID:PMC6081611

[166] Koutnikova H,Monteiro-Sepulveda M.Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials.BMJ Open2019;9:e017995 PMCID:PMC6475231

[167] Ming J,Xu X.Effectiveness and safety of Bifidobacterium and berberine in human hyperglycemia and their regulatory effect on the gut microbiota: a multi-center, double-blind, randomized, parallel-controlled study.Genome Med2021;13:125 PMCID:PMC8351344

[168] Qian X,Lin G.Bifidobacterium adolescentis is effective in relieving type 2 diabetes and may be related to its dominant core genome and gut microbiota modulation capacity.Nutrients2022;14:2479 PMCID:PMC9227778

[169] Chen J,Li XF.Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome.Br J Nutr2012;107:1429-34

[170] Wang B,Cui S.Bifidobacterium adolescentis isolated from different hosts modifies the intestinal microbiota and displays differential metabolic and immunomodulatory properties in mice fed a high-fat diet.Nutrients2021;13:1017 PMCID:PMC8004121

[171] Taipale TJ,Isolauri E,Söderling EM.Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in early childhood.Pediatr Res2016;79:65-9

[172] Taipale TJ,Isolauri E.Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in infancy.Br J Nutr2011;105:409-16

[173] Dekker J,Qian H.Comparison of two probiotics in follow-on formula: Bifidobacterium animalis subsp. lactis HN019 reduced upper respiratory tract infections in Chinese infants.Benef Microbes2022;13:341-54

[174] Hevia A,López P.Allergic patients with long-term asthma display low levels of Bifidobacterium adolescentis.PLoS One2016;11:e0147809 PMCID:PMC4739579

[175] Casaro MC,Vieira AT.Prophylactic Bifidobacterium adolescentis ATTCC 15703 supplementation reduces partially allergic airway disease in Balb/c but not in C57BL/6 mice.Benef Microbes2018;9:465-76

[176] Fan Z,Ross RP.Protective effects of Bifidobacterium adolescentis on collagen-induced arthritis in rats depend on timing of administration.Food Funct2020;11:4499-511

[177] Ferro M,Dourado E,Fonseca JE.Probiotic supplementation for rheumatoid arthritis: a promising adjuvant therapy in the gut microbiome era.Front Pharmacol2021;12:711788 PMCID:PMC8346200

[178] Lin L,Xiong Q.Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression.J Autoimmun2023;141:103001

[179] Bodkhe R,Taneja V.The role of microbiome in rheumatoid arthritis treatment.Ther Adv Musculoskelet Dis2019;11:1759720X19844632 PMCID:PMC6685117

[180] Scher JU.Periodontal disease, Porphyromonas gingivalis, and rheumatoid arthritis: what triggers autoimmunity and clinical disease?.Arthritis Res Ther2013;15:122 PMCID:PMC3978430

[181] Mikuls TR,Reinhardt RA.Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis.Int Immunopharmacol2009;9:38-42 PMCID:PMC2748386

[182] Hojo K,Murata S,Ohshima T.Reduction of vitamin K concentration by salivary Bifidobacterium strains and their possible nutritional competition with Porphyromonas gingivalis.J Appl Microbiol2007;103:1969-74

[183] Li B,Liu X.Bifidobacterium breve CCFM1078 alleviates collagen-induced arthritis in rats via modulating the gut microbiota and repairing the intestinal barrier damage.J Agric Food Chem2022;70:14665-78

[184] Achi SC,Halami PM.Prophylactic effects of probiotic Bifidobacterium spp. in the resolution of inflammation in arthritic rats.Appl Microbiol Biotechnol2019;103:6287-96

[185] Tiller JW.Depression and anxiety.Med J Aust2013;199:S28-31

[186] Góralczyk-Bińkowska A,Kozłowska E.The microbiota-gut-brain axis in psychiatric disorders.Int J Mol Sci2022;23:11245 PMCID:PMC9570195

[187] Gulas E,Strzelecki D,Polguj M.Can microbiology affect psychiatry? A link between gut microbiota and psychiatric disorders.Psychiatr Pol2018;52:1023-39

[188] Alli SR,Liu JCW,Brown L.The gut microbiome in depression and potential benefit of prebiotics, probiotics and synbiotics: a systematic review of clinical trials and observational studies.Int J Mol Sci2022;23:4494 PMCID:PMC9101152

[189] Sarasa SB,Muthusamy G,Selta DRF.A brief review on the non-protein amino acid, gamma-amino butyric acid (GABA): its production and role in microbes.Curr Microbiol2020;77:534-44

[190] Barrett E,O’Toole PW,Stanton C.γ-Aminobutyric acid production by culturable bacteria from the human intestine.J Appl Microbiol2012;113:411-7

[191] Cryan JF.Don’t worry ‘B’ happy!: a role for GABA_B receptors in anxiety and depression.Trends Pharmacol Sci2005;26:36-43

[192] Schousboe A,Sickmann HM,Waagepetersen HS.Energy substrates to support glutamatergic and GABAergic synaptic function: role of glycogen, glucose and lactate.Neurotox Res2007;12:263-8

[193] Allen AP,Borre YE.Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers.Transl Psychiatry2016;6:e939 PMCID:PMC5314114

[194] Kim CS,Sim M.Probiotic supplementation improves cognitive function and mood with changes in gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial.J Gerontol A Biol Sci Med Sci2021;76:32-40 PMCID:PMC7861012

[195] Boehme M,Lerond C.Bifidobacterium longum subsp. longum reduces perceived psychological stress in healthy adults: an exploratory clinical trial.Nutrients2023;15:3122 PMCID:PMC10383821

[196] Wang H,Murphy EF.Bifidobacterium longum 1714^TM strain modulates brain activity of healthy volunteers during social stress.Am J Gastroenterol2019;114:1152-62 PMCID:PMC6615936

[197] Bercik P,Sinclair D.The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication.Neurogastroenterol Motil2011;23:1132-9 PMCID:PMC3413724

[198] Haas GS,Saffar M,Brummelte S.Probiotic treatment (Bifidobacterium longum subsp. longum 35624^TM) affects stress responsivity in male rats after chronic corticosterone exposure.Behav Brain Res2020;393:112718

[199] Tarracchini C,Lugli GA.The Integrated Probiotic Database: a genomic compendium of bifidobacterial health-promoting strains.Microbiome Res Rep2022;1:9 PMCID:PMC10688828

[200] Turroni F,Ventura M.Bifidobacteria: insights into the biology of a key microbial group of early life gut microbiota.Microbiome Res Rep2021;1:2 PMCID:PMC10688781

[201] Gerritsen J,Rijkers GT.Intestinal microbiota in human health and disease: the impact of probiotics.Genes Nutr2011;6:209-40 PMCID:PMC3145058

[202] Ruiz L,Ruas-Madiedo P,Margolles A.Bifidobacteria and their molecular communication with the immune system.Front Microbiol2017;8:2345 PMCID:PMC5722804