Senior author and lead investigator of the clinical trial, Dr. Eliana Marino from Monash University, said the study tested twenty-one adults with type 1 diabetes that incorporated a six-week supplement into their daily diet.
“People with 1 diabetes have shown altered gut microbiota and reduced production of short-chain fatty acids in stools and blood. We previously have demonstrated that the supplement used in this human study protected mice from diabetes (Marino et al., Nat Immunol 2017),” said Dr. Marino.
Short-chain fatty acids (SCFAs) are metabolites produced by the gut microbiota, that greatly affect human health and disease [1]. Mostly produced from fermentation of non-digestible dietary carbohydrates, SCFAs, primarily acetate, propionate, and butyrate, are anti-inflammatory and critical for maintaining gut homeostasis as well as playing a role in host energy metabolism [2].
Indeed, studies in mice and humans have shown that a deficiency in production of SCFAs by the gut microbiota is associated with the development of T1D, starting well before clinical diagnosis [5,6,7,8], which may be linked to altered gut homeostasis [9,10,11].
Insufficient intake of dietary fiber, or a gut microbiota that is poor at SCFA production may underpin the increased incidence of T1D and many other Western diseases [1, 2]. Thus, 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].
Clinical studies have begun to show the potential of modulating the microbiota composition via the use of prebiotics, probiotics, and fecal transplantation as an alternative approach to treat inflammatory diseases [12]. Most microbiota-based therapies identify bacterial communities or pathways associated with disease and then aim to restore specific health-associated species, an approach with inherent caveats.
For example, the wide inter-individual variability in the gut microbiota associated with diseases such as T1D [3, 7] and key factors such as diet and host genetics, which affect microbiota colonization and adaptation, are all barriers to current investigative approaches [13].
Post-biotic targets (metabolites produced by the gut microbiota) have recently emerged as a novel alternative to promote health and circumvent these barriers [14]. We have developed a high-SCFA–yielding dietary supplement that ameliorates gut infection, improves chemotherapy efficacy, and protects mice against T1D via regulating the immune system [5, 10, 15].
The HAMSAB diet prevented beta-cell destruction by T cells and protected against T1D in 90% of NOD mice. Protection against T1D was associated with microbiota composition changes. The mechanism behind this SCFA-induced T1D protection involved synergistic effects of acetate and butyrate; expansion of regulatory T cells (Treg) was butyrate dependent, and a decrease in pathogenic B cells and CD4+ and CD8+ T cells was acetate dependent [5]. Therefore, this dietary intervention targets microbiota–host interactions, nutrition, and phylogeny.
Several human studies support the positive effects of increasing total fiber consumption in the form of high-amylose maize-resistant starch (HAMS) or butyrate-yielding HAMS (HAMSB) supplementation alone in glycemic control [17, 18] or gastrointestinal conditions [19,20,21].
We report the first interventional study in humans with T1D to determine the effects of delivering a combination of dietary acetate and butyrate on the immune system via the gut microbiota. We therefore, conducted a single-arm pilot-and-feasibility study using HAMSAB administered for 6 weeks with follow-up at 12 weeks in adults with long-standing T1D.
More information: Kirstine J. Bell et al, Metabolite-based dietary supplementation in human type 1 diabetes is associated with microbiota and immune modulation, Microbiome (2022). DOI: 10.1186/s40168-021-01193-9
