TOPLINE:

Patients with celiac disease had a reduced ability to metabolize dietary fiber in the small intestine due to a depletion of fiber-degrading microbes, such as Prevotella spp., regardless of treatment with a gluten-free diet. In preclinical mouse models, introducing microbes from the Prevotellaceae family together with a diet enriched in the soluble fiber inulin increased small intestinal levels of short-chain fatty acids, metabolites that support gut health and mucosal healing.

METHODOLOGY:

• Although a lifelong gluten‑free diet is the only treatment for celiac disease, it can cause nutrient shortfalls, such as low fiber intake; furthermore, although the duodenal microbiota is altered in patients with celiac disease, its effect on microbial fiber metabolism in the small intestine remains unclear.
• Researchers recruited 53 participants from Canada, including 16 patients newly diagnosed with celiac disease within the past 3 months, 11 patients treated with a gluten-free diet for 2 or more years, and 26 healthy control individuals, for duodenal aspirate and fecal sample collection.
• Duodenal microbiota composition was assessed via 16S ribosomal RNA gene sequencing, fecal short-chain fatty acids were measured as a marker of fiber fermentation using gas chromatography-mass spectrometry, and dietary intake was assessed using a food frequency questionnaire and through sequencing of plant DNA from fecal samples.
• In mouse experiments, genetically susceptible nonobese diabetic DQ8 mice were sensitized to gluten to induce small intestinal immune responses and subsequently fed a gluten-free diet with no added fiber or supplemented with either the soluble fiber inulin or the resistant starch Hylon VII; in separate germ-free experiments, mice were colonized with 10 Prevotellaceae strains, and small intestinal short-chain fatty acid production on an inulin-supplemented gluten-free diet was compared with that in noncolonized control mice.
• The study outcomes included duodenal microbial composition and predicted abundance of specific fiber‑degrading enzymes in humans and small intestinal short-chain fatty acid production in mice.

TAKEAWAY:

• Patients with newly diagnosed celiac disease had lower duodenal alpha-diversity than control individuals; those with celiac disease showed a reduced relative abundance of bacteria from the Prevotellaceae family in the duodenum, regardless of treatment with a gluten-free diet.
• Patients with newly diagnosed celiac disease had significantly lower levels of total fecal short-chain fatty acids, specifically acetic acid, than control individuals (P = .00019); butyric acid levels were lower in both the newly diagnosed and treated celiac disease groups than in the control group.
• In gluten-sensitized DQ8 mice, supplementation with inulin during a gluten-free diet significantly improved histologic parameters compared with no added fiber; inulin, but not Hylon VII, supplementation during the gluten-free diet increased small intestinal short-chain fatty acids — primarily acetate — in these mice.
• Colonization of germ-free mice with a collection of Prevotella spp. combined with dietary inulin markedly increased small intestinal short-chain fatty acid concentrations, demonstrating that Prevotella can ferment soluble dietary fiber into short-chain fatty acids in the small intestine when an appropriate substrate is present.

IN PRACTICE:

“Our study provides clinical evidence that the small intestinal microbiota in CeD [celiac disease] contains less fiber-degrading bacteria, such as Prevotellaceae, independently of diet, and provides preclinical evidence that certain fibers could be used as adjuvant therapy for the GFD [gluten-free diet] to promote mucosal healing when metabolizing taxa are present,” the authors of the study wrote.

SOURCE:

The study was led by Mark Wulczynski, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. It was published online in Nature Communications.

LIMITATIONS:

The human cohort was small and exploratory, with limited sample sizes. The food frequency questionnaire was not specifically designed to assess the gluten-free diet, and not all participants completed it. The use of 16S ribosomal RNA gene sequencing rather than shotgun metagenomics may have provided less robust functional analysis.

DISCLOSURES:

The study was supported by a Canadian Institutes of Health Research grant, the US National Institute of Diabetes and Digestive and Kidney Diseases, and other sources. Some authors declared having leadership or committee roles in professional societies, providing consultancy and advisory board roles, co-founding or holding executive positions in commercial ventures, receiving speaker honoraria, obtaining research funding and grants, earning royalties, holding equity or company shares, and serving on professional or foundation boards.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.