Emerging role of the gut microbiome in post-infectious irritable bowel syndrome: A literature review

Table 1 Alterations of the gut microbiota observed during acute gastroenteritis and during post-infectious irritable bowel syndrome

Ref.	Subjects/methods	Sample and techniques	Microbiota alterations	Other findings
Jalanka-Tuovinen et al[51], 2014	11 postinfection IBS, 11 postinfection bowel dysfunction, 12 postinfection without bowel dysfunction, 12 IBS-D, 11 healthy controls adults	16S rRNA gene phylogenetic microarray analysis with HITChip, 16S rRNA gene qPCR with group and species-specific primers of feacal sample	Index of microbial dysbiosis” comprised of 27 genus-like groups including: ↑Bacteroidota including various Bacteroides and Prevotella species, ↓Bacillota including various uncultured Clostridiales, and Clostridium clusters	Dysbiosis was associated with bowel, not psychological symptoms; Dysbiosis associated biopsy findings: ↑eotaxin, mast cells, goblet cells, ↓enterochromaffin cells; Dysbiosis associated RNA expression pathways: ↑serotonin transport, condensed chromosome, B cell antigen receptor, ↓caspase
Hsiao et al[82], 2014	7 adults with V. cholerae AGE history, 50 healthy children, 12 healthy adults	16S rRNA gene PCR, V4 region analysis of faecal sample	One week after AGE: ↑V. cholerae Streptococcus spp Fusobacterium spp Campylobacter spp	Two months after AGE (recovery period): ↓V. cholerae Streptococcus spp Fusobacterium spp Campylobacter spp, ↑species indicating recovery Ruminococcus obeum, Collinsella aerofasciens Ruminococcus torques, Eubacterium rectale Faecalibacterium prausnitzii
Ma et al[83], 2011	13 Adenovirus diarrhea, 13 Rotavirus diarrhea, 13 Astrovirus diarrhea, 13 Norvirus diarrhea, 6 control children	16S rRNA gene PCR, V3 region analysis of faecal sample	↓Diversity in diarrheal patients, ↑Enterococcus, Peptostreptococcaceae, Incertae Sedi, Shigella, Weissella spp	↓Bacteroides vulgatus Bifidobacterium, Lactobacillus spp
Youmans et al[84], 2015	111 all-cause traveler’s diarrhea/12 healthy travelers	16S rRNA gene PCR, V3 and V5 regions analysis of faecal sample	↓Bacteroidota: Bacillota ratio in diarrheal patients; ↑Species diversity during norovirus infection; ↑Clostridium XIVb Bilophilia Alistipes Barnesiella, Roseburia spp during norovirus infection	↑Bacillota phylum Streptococcus Lactococcus spp in healthy travelers (unexpected)
Patin et al[88], 2020	4 symptomatic and 5 asymptomatic norovirus infected adults	16S rRNA gene analysis of faecal sample	Post norovirus challenge: ↑Bacillota phylum, particularly Clostridia, ↓Bacteroidota Pseudomonadota	Prior to norovirus challenge: Asymptomatic patients had ↑Bacteroidota phylum and ↓Clostridia compared to symptomatic
Nelson et al[86], 2012	38 norovirus infection, 22 healthy controls	16S rRNA gene 454 pyrosequencing, V3-V5 regions analysis of faecal sample	A subset (approximately 1/5) patients with norovirus had: ↓diversity, ↑Pseudomonadota phylum, Enterobacteriaceae family	Escherichia coli diversity and virulence was not associated with norovirus infection
Cheng et al[87], 2022	COVID-19 acute and recovery phase; Non COVID-19	Meta-analysis of 16S rRNA microbial data	↓Ruminococcus Faecalibacterium Roseburia, Coprococcus genus, ↑Fusobacterium Streptococcus in recovery/post-recovery COVID-19 compared to non COVID-19	↓Clostridium clostridioforme, ↑Bifidobacterium breve in COVID-19 compared to recovery/post-recovery COVID-19
Liu et al[93], 2022	68 COVID-19 patients, 68 non-COVID-19 patients	Shotgun metagenomic sequencing	At 6 mo follow up 76% developed PACS; Non-PACS showed recovered gut microbiome profile at 6 mo comparable to that of non-COVID-19 controls; ↑Ruminococcus gnavus, Bacteroides vulgatus and ↓Faecalibacterium prausnitzii in PACS	Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlation with PACS at 6 mo
Zuo et al[95], 2020	15 Acute COVID-patients, 6 community acquired pneumonia patients, 15 healthy controls	Shotgun metagenomic sequencing	Antibiotic naïve patients ↑Clostridium hathewayi, Actinomyces viscosus, and Bacteroides nordii compared with controls; COVID-19 with antibiotic use ↓Faecalibacterium prausnitzii, Lachnospiraceae bacterium 5_1_63FAA, Eubacterium rectale, Ruminococcus obeum, and Dorea formicigenerans compared with COVID-19 naïve patients	Baseline abundance of Coprobacillus, Clostridium ramosum, and Clostridium hathewayi correlated with COVID-19 severity: There was an inverse correlation between abundance of Faecalibacterium prausnitzii and disease severity; Depletion of symbionts and enrichment of opportunistic pathogens persisted after clearance of SARS-CoV-2
Yeoh et al[96], 2021	100 COVID-19 patients, 78 non COVID-19 controls	Shotgun sequencing total DNA extraction from stool sample	Patients with COVID-19 were depleted in Faecalibacterium prausnitzii, Eubacterium rectale and several bifidobacterial species, which remain low up to 30 d from disease resolution	Composition of the gut microbiota in patients with COVID-19 is concordant with disease severity and magnitude of plasma concentrations of several inflammatory cytokines, chemokines and blood markers of tissue damage
Sundin et al[99], 2015	13 PI-IBS patients, 19 general IBS patients, 16 healthy controls	HITChip for mucosal and fecal microbiota	↓Mucosal and faecal diversity Bacillota phylum including Clostridium clusters IV and XIVa, ↑Bacteroidota phyum including Bacteroides spp	Reduced diversity was associated with psychological symptoms and increased activated lamina propria lymphocytes. Did not find a difference in major butyrate producer abundance

AGE: Acute gastroenteritis; COVID-19: Coronavirus disease 2019; IBS-D: Diarrhea-predominant irritable bowel syndrome; PACS: Post-acute coronavirus disease 2019 syndrome; PI-IBS: Post-infectious irritable bowel syndrome; qPCR: Quantitative polymerase chain reaction; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.

Table 2 Post-infectious irritable bowel syndrome therapeutic options

Ref.	Therapeutic intervention	Outcome
Compare et al[102], 2017	Lactobacillus casei DG + postbiotic	↓The inflammatory mucosal response in an ex vivo organ culture model of PI-IBS-D
Hong et al[103], 2019	Lactobacillus acidophilus LA5, Bifidobacterium animalis subsp. lactis BB12 and Saccharomyces cerevisiae var. boulardii)	↓Pro-inflammatory cytokine levels in both the control and PI-IBS induced mice
Abbas et al[104], 2014	Saccharomyces boulardii	Improved the quality of life and the cytokine profile in PI-IBS patients
Lee et al[106], 2017	Bifidobacterium infantis	Restored the normal composition of gut microbiota and improved mental health among individuals with post-flood acquired IBS
Cao et al[107], 2018	Lactobacillus rhamnosus supernatant	Had a positive effect on SERT expression in colon tissues of rats with PI-IBS, improving IBS symptoms in PI-IBS rats
Chen et al[108], 2022	Enterococcus faecium and Enterococcus faecalis supernatant, in PI-IBS rats	The supernatants of B. subtilis, Enterococcus faecium, and Enterococcus faecalis can upregulate SERT expression in intestinal epithelial cells and the intestinal tissues in the rat model of PI-IBS
Tkach et al[110], 2022	RCT, low FODMAP diet + Otilonium Bromide + a multi-strain probiotic vs FMT procedure	FMT proved effectiveness in restoring normal gut microbiota and ameliorating PI-IBS symptoms, compared to traditional pharmacotherapy, as well as a high degree of safety and good tolerability
Liu et al[111], 2021	FMT procedure	FMT can partially restore the gut dysbiosis in COVID-19 patients by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT
Jin et al[113], 2017	Rifamixin in PI-IBS rats	Rifaximin alleviated visceral hypersensitivity, recoverd intestinal barrier function and inhibited low-grade inflammation in colon and ileum of PI-IBS rats. Exerts anti-inflammatory effects with only a minimal action on the overall composition and diversity of the gut microbiota
Harris et al[114], 2019	Rifamixin vs placebo in veterans with IBS	Rifaximin was not associated with signifcant improvement in global symptoms, abdominal pain, stool frequency, urgency, bloating, or stool consistency
Tuteja et al[115], 2019	Rifamixin vs placebo in veterans with IBS	Rifaximin was not effective in improving IBS symptoms and QOL in GW veterans with non-constipated IBS
Lam et al[116], 2016	Mesalazine vs placebo	Mesalazine was no better than placebo in relieving symptoms of abdominal discomfort or disturbed bowel habit. Mesalazine did not reduce mast cell percentage area stained. A subgroup of patients with postinfectious IBS may benefit from mesalazine
Bafutto et al[117], 2011	Mesalazine in PI-IBS patients compared to non-infective IBS patients	Mesalazine reduced key symptoms of postinfectious irritable bowel syndrome and noninfective irritable bowel syndrome with diarrhea patients, with no statistical difference between IBS and PI-IBS
Tuteja et al[118], 2012	Mesalazine vs placebo	There was no significant improvement in global symptoms or overall QOL with mesalazine in patients with PI-IBS
Andresen et al[119], 2016	Mesalazine during the AGE with STEC	Mesalazine administration during AGE with STEC might be a protective factor for PI-IBS
Dunlop et al[120], 2003	Prednisolone vs placebo	Prednisolone does not appear to reduce the number of enterochromaffin cells or cause an improvement in symptoms in PI-IBS

AGE: Acute gastroenteritis; FMT: Fecal microbial transplantation; IBS-D: Diarrhea-predominant irritable bowel syndrome; PI-IBS: Post-infectious irritable bowel syndrome; RCT: Randomised controlled trial; QOL: Quality of life; SERT: Serotonin transporter; STEC: Shiga-like toxin-producing Escherichia coli.