DIAGNOSTIC & TREATMENT OVERVIEW

Quigley, E.M.M. Curr Gastroenterol Rep (2019) 21: 3. https://doi.org/10.1007/s11894-019-0671-z
Purpose of Review: To critically review recent (past 3 years) literature on the definition, diagnosis, and management of small intestinal bacterial overgrowth (SIBO). Recent Findings: While various series continue to illustrate the occurrence of SIBO in disease states where well-known risk factors for its occurrence are present (hypochlorhydria, disorders of intestinal structure or motor function, pancreatic insufficiency, and chronic liver disease, for example), the current challenge is in defining the limits of SIBO. Is SIBO truly common among those with “functional” gastrointestinal symptoms where there is no evidence of maldigestion or malabsorption; the original hallmarks of SIBO? Our attempts to address this question continue to be hampered by the limitations of our diagnostic tool kit. There is hope—the application of modern molecular techniques to the study of the small intestinal microbiome, together with some innovative sampling techniques, such as real-time intestinal gas sampling, may soon allow us to truly define the spectrum of SIBO. Summary: SIBO, once removed from its original confines as a cause of malabsorption syndrome, has proven to be an elusive and moving target. Only the most rigorous studies employing validated methodologies will finally corral this mysterious entity.

Rezaie, A., Pimentel, M. & Rao, S.S. Curr Gastroenterol Rep (2016) 18: 8. https://doi.org/10.1007/s11894-015-0482-9
Small intestinal bacterial overgrowth (SIBO) is characterized by an excessive amount of bacteria in the small intestine and a constellation of symptoms that include bloating, pain, gas, and diarrhea. Although known for many decades, there is a lack of consensus and clarity regarding the natural history and methods for its diagnosis. Several tests have been proposed, including the glucose breath test, lactulose breath test, small intestinal aspiration and culture, and others. However, there is a lack of standardization of these tests and their interpretation. Treatment of SIBO remains empirical; generally, broad spectrum antibiotics are recommended for 2 weeks (amoxicillin, rifaximin, ciprofloxacin, etc.) but evidence for their use is fair. Clearly, there is a strong need to develop a systematic approach for the management of SIBO and to perform multicenter clinical trials for the treatment of SIBO. In this review, we will discuss the current evidence for the diagnosis and treatment of SIBO, which includes (1) elimination/modification of the underlying causes, (2) induction of remission (antibiotics and elemental diet), and (3) maintenance of remission (promotility drugs, dietary modifications, repeat or cyclical antibiotics).

Francesca Romana Ponziani, Viviana Gerardi & Antonio Gasbarrini. Diagnosis and treatment of small intestinal bacterial overgrowth. Pages 215-227 | Received 23 Aug 2015, Accepted 15 Oct 2015, Published online: 04 Dec 2015
A huge number of bacteria are hosted in the gastrointestinal tract, following a gradient increasing towards the colon. Gastric acid secretion and intestinal clearance provide the qualitative and quantitative partitioning of intestinal bacteria; small intestinal bacteria overgrowth (SIBO) occurs when these barrier mechanisms fail. Diagnosis of SIBO is challenging due to the low specificity of symptoms, the frequent association with other diseases of the gastrointestinal tract and the absence of optimal objective diagnostic tests. The therapeutic approach to SIBO is oriented towards resolving predisposing conditions, and is supported by antibiotic treatment to restore the normal small intestinal microflora and by modifications of dietary habits for symptomatic relief. In the near future, metagenomics and metabolomics will help to overcome the uncertainties of SIBO diagnosis and the pitfalls of therapeutic management, allowing the design of a personalized strategy based on the direct insight into the small intestinal microbial community.

M. Gabrielli, G. D’angelo, T. Di Rienzo, E. Scarpellini, V. Ojetti. Diagnosis of small intestinal bacterial overgrowth in the clinical practice. Eur Rev Med Pharmacol Sci, Year: 2013, Vol. 17 – N. 2 Suppl Pages: 30-35.
Background: Gut microbiota plays several beneficial effects on the human host. Its qualitative and/or quantitative unbalance may facilitate the occurrence of small intestinal bacterial overgrowth (SIBO). Aim: To review the available data in order to propose a practical approach to SIBO diagnosis in the clinical setting. Materials and Methods: Full papers from 1990 to present available on the Pubmed database concerning the topic of SIBO diagnosis were critically reviewed. Results: SIBO is common in the presence of one or more predisposing conditions. The clinical picture of SIBO patients is extremely variable, depending of underlying disorders, and both patients and microbiota characteristics. SIBO could be asymptomatic, or leading to aspecific gastrointestinal IBS-like symptoms. In worst cases it may configure a real malabsorption syndrome. Culture of intestinal aspirates remains at present the gold standard for SIBO diagnosis. However a lot of limitations including high costs and invasivity prevent from using this test in the clinical practice. Hydrogen lactulose and especially glucose breath tests are at present the most utilized to reach SIBO diagnosis in the clinical setting, due to their low costs, non invasivity, sufficient accuracy and reproducibility. Conclusions: SIBO should be suspected in the presence of IBS-like symptoms and/or malabsorption syndrome occurring in the presence of disorders predisposing to SIBO development. The most common diagnostic tool is represented at present by hydrogen breath tests.

TESTING

Rezaie A, Buresi M, Lembo A, et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am J Gastroenterol. 2017;112(5):775-784.
Objectives: Breath tests (BTs) are important for the diagnosis of carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO). However, standardization is lacking regarding indications for testing, test methodology and interpretation of results. A consensus meeting of experts was convened to develop guidelines for clinicians and research. Methods: Pre-meeting survey questions encompassing five domains; indications, preparation, performance, interpretation of results, and knowledge gaps, were sent to 17 clinician-scientists, and 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and voted on anonymously by a working group of specialists. Results: Consensus was reached on 26 statements encompassing all five domains. Consensus doses for lactulose, glucose, fructose and lactose BT were 10, 75, 25 and 25 g, respectively. Glucose and lactulose BTs remain the least invasive alternatives to diagnose SIBO. BT is useful in the diagnosis of carbohydrate maldigestion, methane-associated constipation, and evaluation of bloating/gas but not in the assessment of oro-cecal transit. A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane-positive. SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion. Conclusions: BT is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. These consensus statements should help to standardize the indications, preparation, performance and interpretation of BT in clinical practice and research.

Yao CK, Tuck CJ, Barrett JS, Canale KE, Philpott HL, Gibson PR. Poor reproducibility of breath hydrogen testing: Implications for its application in functional bowel disorders. United European Gastroenterol J. 2016;5(2):284-292.
Background: Limited data are available regarding the reproducibility of lactulose and fructose breath testing for clinical application in functional bowel disorders. Objectives: The purpose of this study was to investigate the reproducibility of lactulose and fructose breath hydrogen testing and assess symptom response to fructose testing. Methods: Results were analysed from 21 patients with functional bowel disorder with lactulose breath tests and 30 with fructose breath tests who completed another test >2 weeks later. Oro-caecal transit time, hydrogen responses, both qualitatively (positive/negative) and quantitatively (area under the curve (AUC) for hydrogen), were compared between tests. In another 36 patients, data scores for overall abdominal symptoms, abdominal pain, bloating, wind, nausea and fatigue were collected during the fructose test and compared to hydrogen responses. Results: No correlations were found for lactulose AUC (linear regression, p = 0.58) or transit time (Spearman’s p = 0.54) between tests. A significant proportion (30%) lost the presence of fructose malabsorption (p < 0.01). Hydrogen AUC for fructose did not correlate between tests, (r = 0.28, p = 0.17) independent of time between testing (p = 0.82). Whilst patients with fructose malabsorption were more likely to report symptoms than those without (56% vs 17%; p = 0.04), changes in symptom severity were not different (p > 0.05). Conclusions: Routine use of lactulose and fructose breath tests in functional bowel disorder patients is not supported due to its poor reproducibility and low predictive value for symptom responses.

Yao, C. K., and Tuck, C. J. (2017) The clinical value of breath hydrogen testing. Journal of Gastroenterology and Hepatology, 32: 20–22. doi: 10.1111/jgh.13689.
Breath hydrogen testing for assessing the presence of carbohydrate malabsorption is frequently applied to refine dietary restrictions on a low fermentable carbohydrate (FODMAP) diet. Its application has also been extended for the detection of small intestinal bacterial overgrowth. Recently, several caveats of its methodology and interpretation have emerged. A review of the evidence surrounding its application in the management of patients with a functional bowel disorder was performed. Studies were examined to assess limitations of testing methodology, interpretation of results, reproducibility, and how this relates to clinical symptoms. A wide heterogeneity in testing parameters, definition of positive/negative response, and the use of clinically irrelevant doses of test carbohydrate were common methodological limitations. These factors can subsequently impact the sensitivity, specificity, and false positive or negative detection rates. Evidence is also increasing on the poor intra‐individual reproducibility in breath responses with repeated testing for fructose and lactulose. On the basis of these limitations, it is not surprising that the diagnosis of small intestinal bacterial overgrowth based on a lactulose breath test yields a wide prevalence rate and is unreliable. Finally, symptom induction during a breath test has been found to correlate poorly with the presence of carbohydrate malabsorption. The evidence suggests that breath hydrogen tests have limited clinical value in guiding clinical decision for the patient with a functional bowel disorder.

Hydrogen Breath Testing With Measurement of Orocecal Transit for Diagnosis of Small Bowel Bacterial Overgrowth. Deng, YanyongFox, Mark et al. Clinical Gastroenterology and Hepatology, Volume 14, Issue 10, 1511 – 1512
We read with interest the study by Lin et al1 that reported a high rate of false-positive diagnoses of small bowel bacterial overgrowth (SBBO) by glucose hydrogen breath testing (HBT) with nearly 50% of diagnoses being false-positives caused by rapid transit and early colonic fermentation of unabsorbed substrate. This effect was most marked in patients with previous upper gastrointestinal surgery (65% vs 13% in patients without prior surgery).

Erdogan, A. , Rao, S. S., Gulley, D. , Jacobs, C. , Lee, Y. Y. and Badger, C. (2015), Small intestinal bacterial overgrowth: duodenal aspiration vs glucose breath test. Neurogastroenterol. Motil., 27: 481-489. doi:10.1111/nmo.12516
Background: The diagnosis of small intestinal bacterial overgrowth (SIBO) remains challenging. Our aim was to examine the diagnostic yield of duodenal aspiration/culture and glucose breath test (GBT), and effects of gender, race and demographics on prevalence of SIBO. Methods: Patients with unexplained gas, bloating and diarrhea and negative endoscopy, imaging and blood tests were prospectively enrolled in two centers in USA. Randomly, within 1 week each patient underwent both duodenal aspiration/culture and GBT. The diagnostic yield of each test and relationship of symptoms, and effects of ethnicity, age, and gender on prevalence of SIBO were assessed and compared. Key Results: Duodenal culture was positive in 62/139 (44.6%) subjects and GBT was positive in 38/139 (27.3%) subjects with an overall diagnostic agreement of 65.5%. The sensitivity, specificity, positive and negative predictive value of GBT was 42%, 84%, 68%, and 64%, respectively. Ethnicity or gender did not influence SIBO, but SIBO positive patients were older (p = 0.0018). Symptom patterns were similar except bloating was more prevalent in GBT positive and gas in culture positive subjects. Conclusions & Inferences: Duodenal aspiration/culture identifies 45% of patients with suspected SIBO. GBT has lower sensitivity but good specificity for detection of SIBO. There were no ethnic or gender differences in the prevalence of SIBO, but patients with SIBO were older. Because GBT is non‐invasive, it should be considered first in patients with suspected SIBO.

TREATMENT

Probiotics

Changqing Zhong;Changmin Qu;Baoyan Wang;Shuwen Liang;Bolun Zeng, Probiotics for preventing and treating small intestinal bacterial overgrowth: a meta-analysis and systemic review of current evidence. Journal of Clinical Gastroenterology. 51(4):300–311, APR 2017. DOI: 10.1097/MCG.0000000000000814, PMID: 28267052, Issn Print: 0192-0790, Publication Date: 2017/04/01
The present study conducted a meta-analysis and systematic review of current evidence to assess the efficacy of probiotics in preventing or treating small intestinal bacterial overgrowth (SIBO). Relevant studies from PubMed, Embase, and the Cochrane Central Register of Controlled Trials, until May 2016, were assimilated. The prevention efficacy was assessed by the incidence of SIBO in the probiotic group, and the treatment efficacy by the SIBO decontamination rate, reduction in H2 concentration, and symptom improvement. The relative risk (RR) and weighted mean difference (WMD) were used as effect measures and the random-effects model used for meta-analysis. A total of 14 full-text articles and 8 abstracts were included for the systematic review, and 18 studies were eligible for data synthesis. Patients on probiotic usage showed an insignificant trend toward low SIBO incidence [RR=0.54; 95% confidence intervals (CI), 0.19-1.52; P=0.24]. The pooled SIBO decontamination rate was 62.8% (51.5% to 72.8%). The probiotics group showed a significantly higher SIBO decontamination rate than the nonprobiotic group (RR=1.61; 95% CI, 1.19-2.17; P<0.05). Also, the H2 concentration was significantly reduced among probiotic users (WMD=−36.35 ppm; 95% CI, −44.23 to −28.47 ppm; P<0.05). Although probiotics produced a marked decrease in the abdominal pain scores (WMD=−1.17; 95% CI, −2.30 to −0.04; P<0.05), it did not significantly reduce the daily stool frequency (WMD=−0.09; 95% CI, −0.47 to 0.29). Therefore, the present findings indicated that probiotics supplementation could effectively decontaminate SIBO, decrease H2 concentration, and relieve abdominal pain, but were ineffective in preventing SIBO.

Herbal Therapy

Chedid, V., Dhalla, S., Clarke, J. O., Roland, B. C., Dunbar, K. B., Koh, J., … Mullin, G. E. (2014). Herbal Therapy is Equivalent to Rifaximin for the Treatment of Small Intestinal Bacterial Overgrowth. Global Advances in Health and Medicine, 16–24. https://doi.org/10.7453/gahmj.2014.019
Objective: Patients with small intestine bacterial overgrowth (SIBO) have chronic intestinal and extraintestinal symptomatology which adversely affects their quality of life. Present treatment of SIBO is limited to oral antibiotics with variable success. A growing number of patients are interested in using complementary and alternative therapies for their gastrointestinal health. The objective was to determine the remission rate of SIBO using either the antibiotic rifaximin or herbals in a tertiary care referral gastroenterology practice. Design: One hundred and four patients who tested positive for newly diagnosed SIBO by lactulose breath testing (LBT) were offered either rifaximin 1200 mg daily vs herbal therapy for 4 weeks with repeat LBT post-treatment. Results: Three hundred ninety-six patients underwent LBT for suspected SIBO, of which 251 (63.4%) were positive 165 underwent treatment and 104 had a follow-up LBT. Of the 37 patients who received herbal therapy, 17 (46%) had a negative follow-up LBT compared to 23/67 (34%) of rifaximin users (P=.24). The odds ratio of having a negative LBT after taking herbal therapy as compared to rifaximin was 1.85 (CI=0.77-4.41, P=.17) once adjusted for age, gender, SIBO risk factors and IBS status. Fourteen of the 44 (31.8%) rifaximin non-responders were offered herbal rescue therapy, with 8 of the 14 (57.1%) having a negative LBT after completing the rescue herbal therapy, while 10 non-responders were offered triple antibiotics with 6 responding (60%, P=.89). Adverse effects were reported among the rifaximin treated arm including 1 case of anaphylaxis, 2 cases of hives, 2 cases of diarrhea and 1 case of Clostridium difficile. Only one case of diarrhea was reported in the herbal therapy arm, which did not reach statistical significance (P=.22). Conclusion: SIBO is widely prevalent in a tertiary referral gastroenterology practice. Herbal therapies are at least as effective as rifaximin for resolution of SIBO by LBT. Herbals also appear to be as effective as triple antibiotic therapy for SIBO rescue therapy for rifaximin non-responders. Further, prospective studies are needed to validate these findings and explore additional alternative therapies in patients with refractory SIBO.

Rifaximin

Gatta L, Scarpignato C. Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther. 2017;45(5):604-616.
Background: Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterised by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based. Aim: To perform a systematic review and meta‐analysis to summarise evidence about the efficacy and safety of rifaximin to eradicate SIBO in adult patients. Methods: MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for RCTs and observational studies. Furthermore, abstract books of major European, American and Asian gastroenterological meetings were also examined. Results: Thirty‐two studies involving 1331 patients were included. The overall eradication rate according to intention‐to‐treat analysis was 70.8% (95% CI: 61.4–78.2; I 2 = 89.4%) and to per protocol analysis 72.9% (95% CI: 65.5–79.8; I 2 = 87.5%). Meta‐regression identified three covariates (drug dose, study design and co‐therapy) independently associated with an increased eradication rate. The overall rate of adverse events was 4.6% (95% CI: 2.3–7.5; I 2 = 63.6%). In the subset of studies (n= 10) allowing the analysis, improvement or resolution of symptoms in patients with eradicated SIBO was found to be 67.7% (95% CI: 44.7–86.9; I 2 = 91.3%). Conclusions: Rifaximin treatment seems to be effective and safe for the treatment of SIBO. However, the quality of the available studies is generally poor. Well‐designed RCTs are needed to substantiate these findings and to establish the optimal regimen.

Dae J Kang, Genta Kakiyama, et al. Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition. Clinical and Translational Gastroenterology volume 7, page e187 (2016)
Objectives: Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin. Methods: Four germ-free (GF) mice groups were used (1) GF, (2) GF+rifaximin, (3) Humanized with stools from an MHE patient, and (4) Humanized+rifaximin. Mice were followed for 30 days while rifaximin was administered in chow at 100 mg/kg from days 16–30. We tested for ammonia generation (small-intestinal glutaminase, serum ammonia, and cecal glutamine/amino-acid moieties), systemic inflammation (serum IL-1β, IL-6), intestinal barrier (FITC-dextran, large-/small-intestinal expression of IL-1β, IL-6, MCP-1, e-cadherin and zonulin) along with microbiota composition (colonic and fecal multi-tagged sequencing) and function (endotoxemia, fecal bile acid deconjugation and de-hydroxylation). Results: All mice survived until day 30. In the GF setting, rifaximin decreased intestinal ammonia generation (lower serum ammonia, increased small-intestinal glutaminase, and cecal glutamine content) without changing inflammation or intestinal barrier function. Humanized microbiota increased systemic/intestinal inflammation and endotoxemia without hyperammonemia. Rifaximin therapy significantly ameliorated these inflammatory cytokines. Rifaximin also favorably impacted microbiota function (reduced endotoxin and decreased deconjugation and formation of potentially toxic secondary bile acids), but not microbial composition in humanized mice. Conclusions: Rifaximin beneficially alters intestinal ammonia generation by regulating intestinal glutaminase expression independent of gut microbiota. MHE-associated fecal colonization results in intestinal and systemic inflammation in GF mice, which is also ameliorated with rifaximin.

H.L. DuPont, “Rifaximin: An Antibiotic with Important Biologic Effects”, Mini-Reviews in Medicinal Chemistry (2016) 16: 200. https://doi.org/10.2174/1389557515666150722110201
Rifaximin is a poorly absorbed rifamycin drug with unique pharmacokinetic properties: bile solubility making it highly active against pathogenic and non-pathogenic bacterial flora in the bile-rich small bowel and low water solubility making it active only against highly susceptible bacteria, primarily anaerobes, in the aqueous colon. The drug has anti-inflammatory gut mucosal stabilization properties that are important to its sustained effects in non-infectious diseases. Rifaximin is used chronically or recurrently for hepatic encephalopathy and diarrhea-predominant irritable bowel syndrome. Monitoring of long-term use of rifaximin for development of resistance and then determining whether developed resistance is associated with reduced efficacy are needed. Studies of changes of intestinal flora during therapy and the health implications of these changes are also needed.

Gao J, Gillill and MG 3rd, Owyang C. Gut Microbes. Rifaximin, gut microbes and mucosal inflammation: unraveling a complex relationship. 2014 Jul 1;5(4):571-5. doi: 10.4161/gmic.32130.
Rifaximin is a non-systemic, broad-spectrum antibiotic that acts against gram-positive, gram-negative, and anaerobic bacteria. Clinical studies indicate that rifaximin is beneficial in treating irritable bowel syndrome (IBS). The mechanism responsible for the beneficial effects of rifaximin is not clear. In a recent study, we reported that rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus species. These changes prevent gut inflammation and visceral hyperalgesia caused by chronic stress. To more closely mirror human clinical studies in which rifaximin is used to treat IBS symptoms, we performed additional studies and showed that rifaximin reversed mucosal inflammation and barrier dysfunction evoked by chronic stress. These beneficial effects were accompanied by a striking increase in the abundance of Lactobacillaceae and a marked reduction in the number of segmented filamentous bacteria after rifaximin treatment. These microbial changes may contribute to the antiinflammatory effects of rifaximin on the intestinal mucosa.

Low FODMAPs

Marsh, A., Eslick, E.M. & Eslick, G.D. Eur J Nutr (2016) 55: 897. https://doi.org/10.1007/s00394-015-0922-1
Functional gastrointestinal symptoms such as abdominal pain, bloating, distension, constipation, diarrhea and flatulence have been noted in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The diversity of symptoms has meant that finding an effective treatment has been challenging with most treatments alleviating only the primary symptom. A novel treatment option for IBS and IBD currently generating much excitement is the low fermentable, oligo-, di-, mono-saccharides and polyol (FODMAP) diet. The aim of this meta-analysis was to determine the evidence of the efficacy of such a diet in the treatment of functional gastrointestinal symptoms.
Methods: Electronic databases were searched through to March 2015 to identify relevant studies. Pooled odds ratios (ORs) and 95 % confidence intervals were calculated for the effect of a low FODMAP diet on the reduction in IBS [Symptoms Severity Score (SSS)] score and increase in IBS quality of life (QOL) score for both randomized clinical trials (RCTs) and non-randomized interventions using a random-effects model. Results: Six RCTs and 16 non-randomized interventions were included in the analysis. There was a significant decrease in IBS SSS scores for those individuals on a low FODMAP diet in both the RCTs (OR 0.44, 95 % CI 0.25–0.76; I 2 = 35.52, p = 0.00) and non-randomized interventions (OR 0.03, 95 % CI 0.01–0.2; I 2 = 69.1, p = 0.02). In addition, there was a significant improvement in the IBS-QOL score for RCTs (OR 1.84, 95 % CI 1.12–3.03; I 2 = 0.00, p = 0.39) and for non-randomized interventions (OR 3.18, 95 % CI 1.60–6.31; I 2 = 0.00, p = 0.89). Further, following a low FODMAP diet was found to significantly reduce symptom severity for abdominal pain (OR 1.81, 95 % CI 1.13–2.88; I 2 = 0.00, p = 0.56), bloating (OR 1.75, 95 % CI 1.07–2.87; I 2 = 0.00, p = 0.45) and overall symptoms (OR 1.81, 95 % CI 1.11–2.95; I 2 = 0.00, p = 0.4) in the RCTs. In the non-randomized interventions similar findings were observed. Conclusion: The present meta-analysis supports the efficacy of a low FODMAP diet in the treatment of functional gastrointestinal symptoms. Further research should ensure studies include dietary adherence, and more studies looking at greater number of patients and long-term adherence to a low FODMAP diet need to be conducted.

Halmos EP, Christophersen CT, Bird AR, et al Diets that differ in their FODMAP content alter the colonic luminal microenvironment Gut 2015;64:93-100.
Objective: A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial. Design: Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day), and then crossed over to the other diet with ≥21-day washout period. Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled, and pH, short-chain fatty acid concentrations and bacterial abundance and diversity were assessed. Results: Faecal indices were similar in IBS and healthy subjects during habitual diets. The low FODMAP diet was associated with higher faecal pH (7.37 (7.23 to 7.51) vs 7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance (9.63 (9.53 to 9.73) vs 9.83 (9.72 to 9.93) log10 copies/g; p<0.001) compared with the Australian diet. To indicate direction of change, in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing Clostridium cluster XIVa (median ratio 6.62; p<0.001) and mucus-associated Akkermansia muciniphila (19.3; p<0.001), and reduced Ruminococcus torques. Conclusions: Diets differing in FODMAP content have marked effects on gut microbiota composition. The implications of long-term reduction of intake of FODMAPs require elucidation.