Metabolite-based dietary supplementation in human type 1 diabetes is associated with microbiota and immune modulation

Abstract

Background Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Here, we addressed whether a metabolite-based dietary supplement has an impact on humans with T1D. We conducted a single-arm pilot-and-feasibility trial with high-amylose maize-resistant starch modified with acetate and butyrate (HAMSAB) to assess safety, while monitoring changes in the gut microbiota in alignment with modulation of the immune system status. Results HAMSAB supplement was administered for 6 weeks with follow-up at 12 weeks in adults with long-standing T1D. Increased concentrations of SCFA acetate, propionate, and butyrate in stools and plasma were in concert with a shift in the composition and function of the gut microbiota. While glucose control and insulin requirements did not change, subjects with the highest SCFA concentrations exhibited the best glycemic control. Bifidobacterium longum, Bifidobacterium adolescentis, and vitamin B7 production correlated with lower HbA1c and basal insulin requirements. Circulating B and T cells developed a more regulatory phenotype post-intervention. Conclusion Changes in gut microbiota composition, function, and immune profile following 6 weeks of HAMSAB supplementation were associated with increased SCFAs in stools and plasma. The persistence of these effects suggests that targeting dietary SCFAs may be a mechanism to alter immune profiles, promote immune tolerance, and improve glycemic control for the treatment of T1D. Trial registration ACTRN12618001391268. Registered 20 August 2018,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375792

The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17/Treg balance and gut-lung axis microbiota

“…On the other hand, Treg cell depletion from the intestinal lamina propria in mice influenced the intestinal microbiota composition [ 48 ]. And reduced SCFA production is commonly associated with chronic autoimmune diseases in humans[ 52 ]. A significant inflammation in the lung can also sickly transform the pulmonary microbiota composition in COPD patients [ 53 ].…”

Microbial influencers: treating diabetes through the gut

“…The pilot study by Bell et al 7 . did not observe any changes in markers of glycemic control following the intervention.…”

“…In a recent study published in Microbiome , Bell et al 7 . report on a 6‐week open label single‐arm pilot and feasibility study in patients with T1DM, using a resistant starch fiber supplement in which SCFAs had been esterified, with the aim of delivering a high SCFA load to the colon.…”

“…A major strength of the study by Bell et al 7 . was the use of mass cytometry, a state‐of‐the‐art technology in single‐cell multiparametric analysis, which utilizes mass spectrometry for simultaneous detection of multiple metal‐tagged antibodies bound to phenotypic immune markers.…”

The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease

“…Resistant starch that has been chemically modified to release additional acetate and butyrate in the colon has recently been reported to induce a regulatory immune phenotype in a small cohort of Type-1 diabetes patients ( 283 ). Consumption of 40 g/day of chemically modified high-amylose maize starch for 6 weeks increased the proportion of peripheral blood Treg cells, CTLA-4 expressing T cells and reduced the proportion of CD86 expressing on dendritic cells.…”