Gut microbiota signatures and modulation in irritable bowel syndrome

Abstract

Irritable bowel syndrome (IBS) affects approximately one tenth of the general population and is characterized by abdominal pain associated with abnormalities in bowel habits. Visceral hypersensitivity, abnormal intestinal motor function, mucosal immune activation, and increased intestinal permeability concur to its pathophysiology. Psychological factors can influence symptom perception at the central nervous system level. In addition, recent evidence suggests that dysbiosis may be a key pathophysiological factor in patients with IBS. Increasing understanding of the pathophysiological mechanisms translates into new and more effective therapeutic approaches. Indeed, in line with this evidence, IBS therapies nowadays include agents able to modulate gut microbiota function and composition, such as diet, prebiotics, probiotics, and antibiotics. In addition, in the last decade, an increasing interest in fecal microbiota transplantation has been paid. An in-depth understanding of the intestinal microenvironment through accurate faucal microbiota and metabolite analysis may provide valuable insights into the pathophysiology of IBS, finally shaping new tailored IBS therapies.

Keywords

Gut microbiota / metabolome / irritable bowel syndrome / diarrhea

References

[1] Mearin F,Chang L.Bowel disorders.Gastroenterology2016;

[2] Sperber AD,Drossman DA.Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome foundation global study.Gastroenterology2021;160:99-114.e3

[3] Bhattarai Y,Kashyap PC.Irritable bowel syndrome: a gut microbiota-related disorder?.Am J Physiol Gastrointest Liver Physiol2017;312:G52-62 PMCID:PMC5283907

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

[5] Di Biase AR,Ravaioli F.Gut microbiota signatures and clinical manifestations in celiac disease children at onset: a pilot study.J Gastroenterol Hepatol2021;36:446-54

[6] Barbara G,Bercik P.Rome foundation working team report on post-infection irritable bowel syndrome.Gastroenterology2019;156:46-58.e7 PMCID:PMC6309514

[7] Nistal E,Herrán AR.Differences of small intestinal bacteria populations in adults and children with/without celiac disease: effect of age, gluten diet, and disease.Inflamm Bowel Dis2012;18:649-56

[8] Belkaid Y.Role of the microbiota in immunity and inflammation.Cell2014;157:121-41 PMCID:PMC4056765

[9] Cerf-Bensussan N.The immune system and the gut microbiota: friends or foes?.Nat Rev Immunol2010;10:735-44

[10] Manson JM,Gilmore MS.The commensal microbiology of the gastrointestinal tract.Adv Exp Med Biol2008;635:15-28

[11] Barbara G,Ghoshal UC.The intestinal microenvironment and functional gastrointestinal disorders.Gastroenterology2016;

[12] Lacy BE,Brenner DM.ACG clinical guideline: management of irritable bowel syndrome.Am J Gastroenterol2021;116:17-44

[13] Patel P,Morgan DG.Irritable bowel syndrome is significantly associated with somatisation in 840 patients, which may drive bloating.Aliment Pharmacol Ther2015;41:449-58

[14] Aziz I,Törnblom H,Whitehead WE.The prevalence and impact of overlapping Rome IV-diagnosed functional gastrointestinal disorders on somatization, quality of life, and healthcare utilization: a cross-sectional general population study in three countries.Am J Gastroenterol2018;113:86-96

[15] Zamani M,Zamani V.Systematic review with meta-analysis: the prevalence of anxiety and depression in patients with irritable bowel syndrome.Aliment Pharmacol Ther2019;50:132-43

[16] Sperber AD,Hungin AP.Conducting multinational, cross-cultural research in the functional gastrointestinal disorders: issues and recommendations. A Rome Foundation working team report.Aliment Pharmacol Ther2014;40:1094-102

[17] Lovell RM.Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis.Clin Gastroenterol Hepatol2012;10:712-21.e4

[18] Jafri W,Jafri N,Ali Q.Irritable bowel syndrome and health seeking behaviour in different communities of Pakistan.J Pak Med Assoc2007;57:285-7

[19] Flacco ME,De Giorgio R.Costs of irritable bowel syndrome in European countries with universal healthcare coverage: a meta-analysis.Eur Rev Med Pharmacol Sci2019;23:2986-3000

[20] Sperber AD,Fukudo S.The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review.Gut2017;66:1075-82

[21] Cremon C,Pallotti F.Salmonella gastroenteritis during childhood is a risk factor for irritable bowel syndrome in adulthood.Gastroenterology2014;147:69-77

[22] Card T,Barbara G.Post-infectious IBS: defining its clinical features and prognosis using an internet-based survey.United European Gastroenterol J2018;6:1245-53 PMCID:PMC6169057

[23] Donnachie E,Mehring M.Incidence of irritable bowel syndrome and chronic fatigue following GI infection: a population-level study using routinely collected claims data.Gut2018;67:1078-86

[24] Palsson OS,Turner MJ.IBS patients show frequent fluctuations between loose/watery and hard/lumpy stools: implications for treatment.Am J Gastroenterol2012;107:286-95 PMCID:PMC3855407

[25] Pace F,Bollani S.Inflammatory bowel disease versus irritable bowel syndrome: a hospital-based, case-control study of disease impact on quality of life.Scand J Gastroenterol2003;38:1031-8

[26] Buono JL,Flores NM.Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea.Health Qual Life Outcomes2017;15:35 PMCID:PMC5310011

[27] Nicholl BI,Macfarlane GJ.Psychosocial risk markers for new onset irritable bowel syndrome--results of a large prospective population-based study.Pain2008;137:147-55 PMCID:PMC2441776

[28] 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

[29] Vasant DH,Black CJ.British Society of Gastroenterology guidelines on the management of irritable bowel syndrome.Gut2021;70:1214-40

[30] Camilleri M.Diagnosis and treatment of irritable bowel syndrome: a review.JAMA2021;325:865-77

[31] Ford AC,Corsetti M.Irritable bowel syndrome.Lancet2020;396:1675-88

[32] Drossman DA.Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV.Gastroenterology2016;

[33] Barbara G,Fuschi D.Inflammatory and microbiota-related regulation of the intestinal epithelial barrier.Front Nutr2021;8:718356 PMCID:PMC8475765

[34] Maxwell PR,Kumar D.Antibiotics increase functional abdominal symptoms.Am J Gastroenterol2002;97:104-8

[35] Ford AC,Lacy BE,Moayyedi P.Systematic review with meta-analysis: the efficacy of prebiotics, probiotics, synbiotics and antibiotics in irritable bowel syndrome.Aliment Pharmacol Ther2018;48:1044-60

[36] Bäckhed F,Sonnenburg JL,Gordon JI.Host-bacterial mutualism in the human intestine.Science2005;307:1915-20

[37] Rajilić-Stojanović M.The first 1000 cultured species of the human gastrointestinal microbiota.FEMS Microbiol Rev2014;38:996-1047 PMCID:PMC4262072

[38] Costello EK,Hamady M,Gordon JI.Bacterial community variation in human body habitats across space and time.Science2009;326:1694-7 PMCID:PMC3602444

[39] Sender R,Milo R.Revised estimates for the number of human and bacteria cells in the body.PLoS Biol2016;14:e1002533 PMCID:PMC4991899

[40] Underhill DM.Immune interactions with pathogenic and commensal fungi: a two-way street.Immunity2015;43:845-58 PMCID:PMC4865256

[41] Shkoporov AN,Sutton TDS.The human gut virome is highly diverse, stable, and individual specific.Cell Host Microbe2019;26:527-541.e5

[42] Hooper LV,Macpherson AJ.Interactions between the microbiota and the immune system.Science2012;336:1268-73 PMCID:PMC4420145

[43] LeBlanc JG,de Giori GS,van Sinderen D.Bacteria as vitamin suppliers to their host: a gut microbiota perspective.Curr Opin Biotechnol2013;24:160-8

[44] Bäumler AJ.Interactions between the microbiota and pathogenic bacteria in the gut.Nature2016;535:85-93 PMCID:PMC5114849

[45] Carroll IM,Siddle JP.Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome.Neurogastroenterol Motil2012;24:521-30, e248 PMCID:PMC3975596

[46] Jeffery IB,O'Herlihy E.Differences in fecal microbiomes and metabolomes of people with vs without irritable bowel syndrome and bile acid malabsorption.Gastroenterology2020;158:1016-28.e8

[47] Hollister EB,Shulman RJ.Relationships of microbiome markers with extraintestinal, psychological distress and gastrointestinal symptoms, and quality of life in women with irritable bowel syndrome.J Clin Gastroenterol2020;54:175-83 PMCID:PMC6387862

[48] Duan R,Wang B.Alterations of gut microbiota in patients with irritable bowel syndrome based on 16S rRNA-targeted sequencing: a systematic review.Clin Transl Gastroenterol2019;10:e00012 PMCID:PMC6407812

[49] Pittayanon R,Yuan Y.Gut Microbiota in patients with irritable bowel syndrome-a systematic review.Gastroenterology2019;157:97-108

[50] Tap J,Törnblom H.Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome.Gastroenterology2017;152:111-23.e8

[51] Mars RAT,Ward T.Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome.Cell2020;182:1460-73.e17 PMCID:PMC8109273

[52] Tan J,Potamitis M,Mackay CR.The role of short-chain fatty acids in health and disease.Adv Immunol2014;121:91-119

[53] Gargari G,Gardana C.Fecal Clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome.Environ Microbiol2018;20:3201-13

[54] Sun Q,Song L.Alterations in fecal short-chain fatty acids in patients with irritable bowel syndrome: a systematic review and meta-analysis.Medicine (Baltimore)2019;98:e14513 PMCID:PMC6408019

[55] Pozuelo M,Santiago A.Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome.Sci Rep2015;5:12693 PMCID:PMC4523847

[56] Rajilić-Stojanović M,Salonen A.Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?.Am J Gastroenterol2015;110:278-87 PMCID:PMC4317767

[57] Cremon C,Gargari G.Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: a pilot randomized clinical trial.United European Gastroenterol J2018;6:604-13 PMCID:PMC5987284

[58] Ahluwalia B,Magnusson MK.A distinct faecal microbiota and metabolite profile linked to bowel habits in patients with irritable bowel syndrome.Cells2021;10:1459 PMCID:PMC8230381

[59] Singh P.Emerging role of the gut microbiome in irritable bowel syndrome.Gastroenterol Clin North Am2021;50:523-45

[60] Dionne J,Yuan Y.A systematic review and meta-analysis evaluating the efficacy of a gluten-free diet and a low FODMAPs diet in treating symptoms of irritable bowel syndrome.Am J Gastroenterol2018;113:1290-300

[61] van Lanen AS,Greyling A.Efficacy of a low-FODMAP diet in adult irritable bowel syndrome: a systematic review and meta-analysis.Eur J Nutr2021;60:3505-22 PMCID:PMC8354978

[62] Vervier K,Kumar N.Two microbiota subtypes identified in irritable bowel syndrome with distinct responses to the low FODMAP diet.Gut2021;

[63] Bennet SMP,Störsrud S.Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs.Gut2018;67:872-81

[64] Turck D,De Henauw S.EFSA Panel on NutritionNovel Foods and Food Allergens (NDA)Green kiwifruit (lat. Actinidia deliciosa var. Hayward) and maintenance of normal defecation: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006.EFSA J2021;19:e06641 PMCID:PMC8193538

[65] Caballero N,Ansell J.The effect of green kiwifruit on gas transit and tolerance in healthy humans.Neurogastroenterol Motil2020;32:e13874 PMCID:PMC7507131

[66] 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

[67] 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

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

[69] Barbara G,Azpiroz F.Probiotics in irritable bowel syndrome: where are we?.Neurogastroenterol Motil2018;30:e13513

[70] Su GL,Bercik P.AGA clinical practice guidelines on the role of probiotics in the management of gastrointestinal disorders.Gastroenterology2020;159:697-705

[71] Preidis GA,Kashyap PC.AGA technical review on the role of probiotics in the management of gastrointestinal disorders.Gastroenterology2020;159:708-38.e4 PMCID:PMC8018518

[72] 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

[73] Pimentel M,Chey WD.TARGET Study GroupRifaximin therapy for patients with irritable bowel syndrome without constipation.N Engl J Med2011;364:22-32

[74] Lembo A,Rao SS.Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome.Gastroenterology2016;151:1113-21

[75] Ponziani FR,D'Aversa F,Gasbarrini A.Eubiotic properties of rifaximin: disruption of the traditional concepts in gut microbiota modulation.World J Gastroenterol2017;23:4491-9 PMCID:PMC5504364

[76] Bajaj JS,DuPont HL,Gasbarrini A.New concepts on intestinal microbiota and the role of the non-absorbable antibiotics with special reference to rifaximin in digestive diseases.Dig Liver Dis2018;50:741-9

[77] Cammarota G,Tilg H.European FMT Working GroupEuropean consensus conference on faecal microbiota transplantation in clinical practice.Gut2017;66:569-80 PMCID:PMC5529972

[78] Barbara G.Faecal microbial transplantation in IBS: ready for prime time?.Gut2020;69:795-6

[79] Ianiro G,Black CJ,Cammarota G.Systematic review with meta-analysis: efficacy of faecal microbiota transplantation for the treatment of irritable bowel syndrome.Aliment Pharmacol Ther2019;50:240-8

[80] El-Salhy M,Gilja OH,Hausken T.Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study.Gut2020;69:859-67 PMCID:PMC7229896