The impact of dietary fermentable carbohydrates on a postinflammatory model of irritable bowel syndrome

Abstract

Background A low fermentable carbohydrate (FODMAP) diet is used in quiescent inflammatory bowel disease when irritable bowel syndrome‐like symptoms occur. There is concern that the diet could exacerbate inflammation by modifying microbiota and short‐chain fatty acid (SCFA) production. We examined the effect of altering dietary FODMAP content on inflammation in preclinical inflammatory models. Methods C57BL/6 mice were given 3% dextran sodium sulfate (DSS) in drinking water for 5 days and recovered for 3 weeks (postinflammatory, n = 12), or 5 days (positive‐control, n = 12). Following recovery, DSS‐treated or control mice (negative‐control, n = 12) were randomized to 2‐week low‐ (0.51 g/100 g total FODMAP) or high‐FODMAP (4.10 g) diets. Diets mimicked human consumption containing fructose, sorbitol, galacto‐oligosaccharide, and fructan. Colons were assessed for myeloperoxidase (MPO) activity and histological damage. Supernatants were generated for perforated patch‐clamp recordings and cytokine measurement. Cecum contents were analyzed for microbiota, SCFA, and branched‐chain fatty acids (BCFA). Data were analyzed by two‐way ANOVA with Bonferroni. Key results Inflammatory markers were higher in the positive‐control compared with negative‐control and postinflammatory groups, but no differences occurred between the two diets within each treatment (MPO P > .99, histological scores P > .99, cytokines P > .05), or the perforated patch‐clamp recordings (P > .05). Microbiota clustered mainly based on DSS exposure. No difference in SCFA content occurred. Higher total BCFA occurred with the low‐FODMAP diet in positive‐control (P < .01) and postinflammatory groups (P < .01). Conclusions and inferences In this preclinical study, reducing dietary FODMAPs did not exacerbate nor mitigate inflammation. Microbiota profile changes were largely driven by inflammation rather than diet. Low FODMAP intake caused a shift toward proteolytic fermentation following inflammation.

Nutritional profile of rodent diets impacts experimental reproducibility in microbiome preclinical research

“…Controversy exists over the role of acetic acid, with some studies indicating a therapeutic role in lowering cholesterol and triglyceride production 59 , whereas others have reported a negative correlation to de novo cholesterogenesis and lipogenesis 60 . BCFA content was also impacted, more specifically, iso-valeric acid and iso-butyric acid levels were highest in Group C, which correlates with previous findings in mice given a low FODMAP diet compared to those given a high FODMAP diet 18 . The production of BCFAs primarily arises from microbial fermentation of undigestible protein.…”

“…Gluten determination (µg/mg) www.nature.com/scientificreports/ the colonic microenvironment due to other end-products of protein fermentation such as hydrogen sulphide and ammonia 10 . Additionally, the higher pH in Group C compared to the other groups indicates lower rates of carbohydrate fermentation, which correlates with previous findings that a low FODMAP diet increases pH 18 , and that fructan significantly decreases pH indicating increased fermentation 63 . Overall, the differences seen in SCFA, BCFA, and pH have implications for the reproducibility of rodent studies.…”

“…As a focus in this study, FODMAP and gluten content were measured, and while these were different between diets, no conclusions can be drawn as to which component(s) of the commercially available diets had key influence on the observed differences in microbiota and fermentation patterns. Based on our previous studies using the custom low-FODMAP and custom high-FODMAP purified ingredient diets, streptococcaceae was lower in control mice fed the high-FODMAP diet compared to control mice fed the low-FODMAP diet 18 , suggesting that the changes to the microbiota seen in the current study may have been in part driven by the differences in FODMAP content. However, due to the variation in many aspects of the diets such as macronutrient sources and percentage contribution, the results cannot elucidate the specific dietary compositional factors driving change.…”

“…Normal distribution was determined by D' Agustino-Pearson omnibus normality test, Shapiro-Wilk test and Kolmogorov-Smirnov test with Dallal-Wilkinson-Lillie correction. A p value ≤ 0.05 was selected to reject the null hypothesis by 2-tailed tests 18 . Microbiota analyses were conducted using either QIIME1 29 , MaAsLin (Multivariate Analysis by Linear Models) 30 , Phyloseq package (1.24) 31,32 for R (3.5), and SPSS software 23 (SPSS Inc., IL, USA).…”

“…The FODMAP content of the commercial rodent diets was then compared to custom-made low-and high-FODMAP rodent purified ingredient diets that were developed to mimic that of human consumption. The custom-diets were used previously in the laboratory for separate experiments 18 . One purified ingredient diet was designed to be low in FODMAP content (Envigo Teklad Custom Diet TD.170455; Wisconsin, USA), the other designed to be high in FODMAP content (Envigo, Teklad Custom Diet TD.170456; Wisconsin, USA).…”