Fecal microbiota in congenital chloride diarrhea and inflammatory bowel disease

Abstract

Background and aims Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate. Subjects and methods We recruited 30 patients with CLD for an observational 3-week follow-up study. Thereafter, 16 consented to oral butyrate substitution for a 3-week observational period. Fecal samples, collected once a week, were assayed for calprotectin and potential markers of inflammation, and studied by 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing and compared to that of 19 healthy controls and 43 controls with Crohn’s disease. Data on intestinal symptoms, diet and quality of life were collected. Results Patients with CLD had increased abundances of Proteobacteria, Veillonella, and Prevotella, and lower abundances of normally dominant taxa Ruminococcaceae and Lachnospiraceae when compared with healthy controls and Crohn´s disease. No major differences in fecal microbiota were found between CLD and CLD-associated IBD (including two with yet untreated IBD). Butyrate was poorly tolerated and showed no major effects on fecal microbiota or biomarkers in CLD. Conclusions Fecal microbiota in CLD is different from that of healthy subjects or Crohn´s disease. Unexpectedly, no changes in the microbiota or fecal markers characterized CLD-associated IBD, an entity with high frequency among patients with CLD.

Bicarbonate secretion and acid/base sensing by the intestine

“…Consistent with these observations, the oral application of butyrate to patients did not result in an improvement of the CLD biomarkers [190]. However, one pediatric center was able to apply surprisingly high doses of oral butyrate to CLD children and normalize their stool and serum parameters [18,40].…”

“…However, an oral application of butyrate salt or of tributyrin did not significantly increase the cecal and colonic SCFA levels and did not reverse the diarrhea in slc26a3 −/− mice (Ye, Zhenghao and Kini, Archana, unpublished observations), demonstrating that even high doses of butyrate, taken orally, are completely absorbed in the small intestine of mice. Consistent with these observations, the oral application of butyrate to patients did not result in an improvement of the CLD biomarkers [ 190 ].…”

Causal relationship between the gut microbiome and basal cell carcinoma, melanoma skin cancer, ease of skin tanning: evidence from three two-sample mendelian randomisation studies

“…Ruminiclostridium5 and Ruminococcaceae UCG014 genera correlate positively with the amounts of butyric and valeric acid in the intestines ( 56 ), playing a critical role in maintaining intestinal homeostasis ( 57 , 58 ). Various experimental results ( 59 – 61 ) suggest that when tumor cell lines are exposed to butyric acid, it can induce cancer cell apoptosis, inhibit cellular proliferation, and promote further differentiation of phenotypes.…”

Fatty acids and lipid mediators in inflammatory bowel disease: from mechanism to treatment

“…Oral microencapsulated sodium butyrate has been found to lower calprotectin levels, sustain remission, enhance quality of life and promote SCFA-producing bacteria in IBD patients ( 239 ). Nevertheless, issues of potential poor tolerance to butyrate salts have been raised ( 240 ). The use of an herbal mixture containing chamomile flowers and charcoal has demonstrated an ability to elevate butyrate concentrations in UC patients, resulting in reduced relapses ( 241 ).…”