Abstract
BackgroundShort-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.ResultsHAMSAB 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.ConclusionChanges 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 registrationACTRN12618001391268. Registered 20 August 2018,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375792CkvdGnDkuZG7nQTZ5dAk_pVideo
Highlights
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
Clinical characteristics and protocol adherence The primary outcome of our study was to determine the safety and feasibility of delivery of a HAMSAB dietary supplement in adults with T1D, while the secondary outcomes included determining the effects of the supplement on glycemic control, the gut microbiota, and immune cell function
HAMSAB supplementation was followed by increased circulating marginal zone B cells with a lower activation status Previously, we reported that increasing SCFAs in nonobese diabetic (NOD) mice modulated autoimmune B and T cell responses in T1D, and this was associated with protection against disease [5]
Summary
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 ben‐ eficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Short-chain fatty acids (SCFAs) are metabolites produced by the gut microbiota, that greatly affect human health and disease [1]. Reduced SCFA production is an indicator of a loss of beneficial bacteria (dysbiosis), which is commonly associated with chronic autoimmune and inflammatory diseases including type 1 diabetes (T1D) and type 2 diabetes [3, 4]. A microbiota-targeted dietary intervention that tackles the underlying functional dysbiosis (i.e., deficiency of SCFAs and altered microbiota function) may have great potential in humans to prevent or treat T1D, as it does in autoimmune diabetes-prone nonobese diabetic (NOD) mice [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
