Contribution of Colonic Fermentation and Fecal Water Toxicity to the Pathophysiology of Lactose-Intolerance

Abstract

Whether or not abdominal symptoms occur in subjects with small intestinal lactose malabsorption might depend on differences in colonic fermentation. To evaluate this hypothesis, we collected fecal samples from subjects with lactose malabsorption with abdominal complaints (LM-IT, n = 11) and without abdominal complaints (LM-T, n = 8) and subjects with normal lactose digestion (NLD, n = 15). Lactose malabsorption was diagnosed using a 13C-lactose breath test. Colonic fermentation was characterized in fecal samples at baseline and after incubation with lactose for 3 h, 6 h and 24 h through a metabolomics approach using gas chromatography-mass spectrometry (GC-MS). Fecal water cytotoxicity was analyzed using a colorimetric assay. Fecal water cytotoxicity was not different between the three groups (Kruskall-Wallis p = 0.164). Cluster analysis of the metabolite patterns revealed separate clusters for NLD, LM-T and LM-IT samples at baseline and after 24 h incubation with lactose. Levels of 5-methyl-2-furancarboxaldehyde were significantly higher in LM-IT and LM-T compared to NLD whereas those of an unidentified aldehyde were significantly higher in LM-IT compared to LM-T and NLD. Incubation with lactose increased short chain fatty acid (SCFA) concentrations more in LM-IT and LM-T compared to NLD. In conclusion, fermentation patterns were clearly different in NLD, LM-IT and LM-T, but not related to differences in fecal water cytotoxicity.

Lactose-Induced Chronic Diarrhea Results From Abnormal Luminal Microbial Fermentation and Disorder of Ion Transport in the Colon

“…In our results, we found that the concentrations of SCFAs in the cecal contents of the model group was significantly decreased compared with that of the control group, which was different from a previous study that showed that an increase in SCFAs resulted in acute ingestion of lactose in vivo and in vitro (He et al, 2006;Windey et al, 2015). Few studies have focused on the effect of chronic lactose intervention on SCFAs, and a recent study (Zhai et al, 2018) found no significant difference in the SCFA concentration of feces after 3 weeks of lactulose intervention in mice, suggesting a different mechanism between acute and chronic ingestion.…”

Predictors of response to a low‐FODMAP diet in patients with functional gastrointestinal disorders and lactose or fructose intolerance

“…Association of outcome with peak gas concentrations, rather than concentration‐time profiles, indicates maximum changes in intestinal distension to be more important for symptoms than total gas load or degree of malabsorption and fermentation . Visceral hypersensitivity due to either peripheral sensitisation or altered endogenous sensory modulation will pre‐dispose to increased symptoms with distension and may be triggered by chemosensitivity to a fermentation product . The resident intestinal microbiome is therefore likely to be an important determinant in FODMAP‐related symptoms and the outcome of a low‐FODMAP diet and a recent small study in children demonstrated a baseline microbiome with greater saccharolytic capacity was associated with a beneficial symptomatic response to a 48 h reduction in FODMAPs .…”

Fecal Fermentation in Irritable Bowel Syndrome: Influence of Dietary Restriction of Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols

“…However, we did not demonstrate a clear relation between SCFA levels and IBS symptoms. Previous investigations have evidenced a possible link between microbial fermentation products and abdominal complaints, as well as extra-intestinal symptoms, both in human studies [8,25,26] and in animal models [27,28]. The major SCFAs - acetic, propionic and n-butyric acids - have been particularly incriminated.…”