Gut microbiota ORIGINAL RESEARCH Gut: first published as 10.1136/gutjnl-2019-318717 on 10 October 2019. Downloaded from No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population Luisa W Hugerth ,1 Anna Andreasson,2,3,4 Nicholas J Talley ,5 Anna M Forsberg,3 Lars Kjellström,6 Peter Thelin Schmidt,3 Lars Agreus,7 Lars Engstrand1,8 ► Additional material is ABSTRact published online only. To view Objective The ethiopathogenesis of irritable bowel Significance of this study please visit the journal online syndrome (IBS) is unknown. While a link to the (http:// dx. doi. org/ 10. 1136/ What is already known on this subject? gutjnl- 2019- 318717). gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive ► Irritable bowel syndrome (IBS) is a functional 1Center for Translational conclusions. We aimed to describe the faecal and bowel disorder of unknown aetiology affecting Microbiome Research, CTMR, up to 15% of the population. Department of Microbiology, mucosa-associated microbiome (MAM) and health Tumour and Cell Biology (MTC), correlates on a community cohort of healthy and IBS ► There may be a link between the gut Karolinska Institutet, Science for individuals with no colonoscopic findings. microbiome and IBS symptoms, since a subset Life Laboratory, Solna, Sweden of patients seems to respond to antibiotics. 2Stress Research Institute, Design The PopCol study recruited a random sample ► Several studies have described gut microbiome Stockholm University, of 3556 adults; 745 underwent colonoscopy. IBS Stockholm, Sweden was defined by Rome IV criteria and organic disease composition in IBS, but found different taxa to 3 Department of Medicine, excluded. 16S rRNA gene sequencing was conducted be over- represented or under- represented. Karolinska University Hospital, on sigmoid biopsy samples from 376 representative ► Pathologies might confound microbiome Solna, Sweden results in IBS studies, however population- 4 individuals (63 IBS cases) and faecal samples from 185 Department of Psychology, studies where pathology has been excluded by Macquarie University, Sydney, individuals (32 IBS cases). New South Wales, Australia colonoscopy have not been conducted yet. 5 Results While sigmoid MAM was dominated by Health, University of Newcastle, Lachnospiraceae, faeces presented a higher relative Callaghan, New South Wales, What are the new findings? Australia abundance of Ruminococcaceae. Microbial richness in ► In a population sample, IBS was not associated 6Gastromottagning City, MAM was linearly correlated to that in faeces from the with an altered microbiome either in stool nor Stockholm, Sweden same individual (R²=0.255, p<3E-11) as was diversity mucosa. 7Center for Family and (R²=0.06, p=0.0022). MAM diversity decreased with ► The degree of heterogeneity observed between Community Medicine, http://gut.bmj.com/ Karolinska Institutet, Stockholm, increasing body mass index (BMI; Pearson’s r=−0.1, IBS patients is higher than that observed Sweden p=0.08) and poorer self-r ated health (r=−0.15, between healthy individuals. 8 Bacteriology, Swedish Institute p=0.007), but no other health correlates. Faecal ► A significant correlation was observed between for Communicable Disease microbiome diversity was correlated to stool consistency microbiome diversity and self-rated health for Control, Stockholm, Sweden (r=−0.16, p=0.043). Several taxonomic groups were both stool and sigmoid biopsies. correlated to age, BMI, depression and self-reported Correspondence to How might it impact on clinical practice in the Professor Lars Engstrand, health, including Coprococcus catus associated with on September 26, 2021 by guest. Protected copyright. Department of Microbiology, lower levels of depression (r=−0.003, p=0.00017). The foreseeable future? Tumor and Cell Biology, degree of heterogeneity observed between IBS patients ► Although commercial testing of stool Karolinska Institutet, 171 77 is higher than that observed between healthy individuals. microbiome is available, such testing in IBS Solna, Sweden; Conclusions No distinct microbial signature was is unlikely to help guide current therapeutic lars. engstrand@ ki. se interventions as IBS did not have a clear observed in IBS. Individuals presenting with low self- microbial signature. Received 18 March 2019 rated health or high BMI have lower gut microbiome Revised 11 September 2019 richness. Accepted 16 September 2019 Published Online First A major area of clinical interest is the role of the 10 October 2019 microbiome in functional gastrointestinal disorders, including the irritable bowel syndrome (IBS).4 IBS INTRODUCTION is estimated to affect 15% of the population, but The pivotal role played by the human micro- its aetiopathogenesis remains unclear.5 In addition biome in health and disease is being increasingly to dietary, behavioural and lifestyle risk factors, 1 2 recognised. At the same time, there is a growing mounting evidence suggests a role for the gut © Author(s) (or their understanding of the heterogeneity of the healthy employer(s)) 2020. Re-use microbiome. Among the indirect evidence for this 6 7 permitted under CC BY-­NC. No human microbiome, which has led to population- is IBS induction or amelioration in response to commercial re-use . See rights based cohorts of faecal microbiome communities, antibiotics. Several studies have attempted to iden- and permissions. Published such as the Flemish Gut Flora and Dutch LifeLines- tify IBS- specific alterations of the gut microbiome by BMJ. Deep studies.3 Without an adequate understanding (reviewed in48). There is, however, still no clearly To cite: Hugerth LW, of which demographic parameters influence the gut delineated IBS gut microbiome profile. Andreasson A, Talley NJ, et al. microbiome, it is difficult to plan adequate studies Most large-scale studies of the human gut micro- Gut 2020;69:1076–1084. into its role in disease. biome have focused on faecal samples. However, 1076 Hugerth LW, et al. Gut 2020;69:1076–1084. doi:10.1136/gutjnl-2019-318717 Gut microbiota the bulk luminal microbial community only partially reflects with a change in frequency of stool and (3) associated with a 9 19 the mucosa- associated microbiome (MAM). While numeri- change in form (appearance) of stool using the ASQ. In total, Gut: first published as 10.1136/gutjnl-2019-318717 on 10 October 2019. Downloaded from cally smaller, the mucosal community’s close association to the 152 IBS cases were identified. host epithelium and its immune system may be more important Four questions were used to define the IBS types: in protecting the host or promoting disease.9 The logistic 1. Do you have looser stools when you have abdominal pain or difficulties in attaining a broad cohort of human gut mucosal discomfort? samples has meant that its role in health has been relatively 2. Do you use the toilet more often when you have abdominal neglected, with published studies settling for low numbers (9–29 pain or discomfort? individuals).10–13 3. Do you have harder stools when you have abdominal pain Here, we take advantage of the PopCol cohort to analyse the or discomfort? faecal and MAM of a representative sample of an adult urban 4. Do you use the toilet less often when you have abdominal population. This study recruited a random sample of 3556 adults pain or discomfort? living in Stockholm, of which 745 agreed to a colonoscopy.14 Volunteers answering ‘yes’ to questions 1 or 2 but neither to During colonoscopy, biopsies of the large bowel were collected. 3 nor 4 were classified as IBS-D. Conversely, those answering Faecal samples were collected in a subset of participants. ‘yes’ to questions 3 or 4 but neither to 1 nor 2 were classified as In addition to these samples, volunteers filled extensive ques- IBS- C. Those who answered ‘yes’ to either one of 1 or 2 as well tionnaires on their health, lifestyle and bowel habits to define as either one of 3 or 4 were classified as IBS-M. The remaining phenotypes. The colonoscopy provided information on disease were labelled IBS- U (unclassified). state, including the presence of polyps, diverticula, and inflam- IBS symptom burden was assessed using the Gastrointestinal mation, as described in previous studies.15–17 However, except Symptom Rating Scale (GSRS).20 for a smaller cohort of faecal samples with a focus on abdominal pain,18, the microbiome of these patients has not been studied. Proxy for stool consistency In the present study, we aimed to compare the sigmoid MAM 21 and faecal microbiome of a representative population- sample. Stool form correlates with colonic transit time. Questions We hypothesised that while the microbial composition of faeces on stool pattern were used to estimate a score, based on the differs from the MAM in an individual, factors specific to each following questions from the ASQ: individual would also be observable. Furthermore, we hypoth- a. Have you had any of the following symptoms at least one- esised that IBS would be characterised by an altered MAM. To fourth of the time (occasions or days) in the last 3 months our knowledge, this is the first study to investigate the mucosa- (check all that apply): associated gut microbiome of an adult population-based cohort. 1. Fewer than three bowel movements a week. 2. More than three bowel movements a day. 3. Hard or lumpy stools. METHODS 4. Loose, mushy or watery stools. Participants b. Did you have loose, mushy or watery stools, during more The present study is part of PopCol, a population- based colonos- than three quarters (3/4) of your bowel movements? http://gut.bmj.com/ copy study previously described in detail.14 A random sample of Questions associated with a faster transit time (a2, a4, b) were 3556 adults living in Stockholm, Sweden, were sent a validated given a score of +1 for each question. Questions associated with Abdominal Symptom Questionnaire (ASQ).19 All responders a slower transit time (a1, a3) were given a score of −1 for each (n=2293) were contacted by phone with an invitation to a question.