The role of short-chain fatty acids on insulin sensitivity: a systematic review and meta-analysis

Context There is substantial evidence that reduced gut short chain fatty acids (SCFAs) are associated with obesity and type 2 diabetes, although findings from clinical interventions that could increase SCFAs are inconsistent. Objective This work aimed to assess the effect of SCFA intervention on fasting glucose, fasting insulin, and HOMA-IR by performing a systematic review and meta-analysis. Data sources Relevant published articles up to 28 th July 2022 were extracted from PubMed and EMBASE using the medical subject heading (MeSH) of the defined keywords [(short-chain fatty acids AND (obesity OR diabetes OR insulin sensitivity)] and their synonyms. Data analyses were performed using recommended Cochrane meta-analysis checklist and PRISMA guidelines and were registered in the PROSPERO system (ID: CRD42021257248). Data extraction Clinical studies and trials that measured SCFAs along with reporting glucose homeostasis parameters were included in the analysis. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model in the data extraction tool Review Manager version 5.4 (RevMan 5.4). The risk of bias assessment was performed following the Cochrane checklist for randomised and crossover studies. Data analysis We identified 6,040 non-duplicate studies; 23 met defined criteria and reported fasting insulin, fasting glucose, or HOMA-IR as well as a measured post-intervention change in SCFA concentrations. Our meta-analyses indicated that fasting insulin concentrations significantly reduced (overall effect: SMD = -0.15; 95% CI = -0.29, -0.01, p = 0.04) between placebo and treatment groups at the end of the intervention. Post-intervention increase in SCFAs had an even significant effect on lowering fasting insulin (p=0.008). Elevated levels of SCFAs were also associated with beneficial effects on HOMA-IR (p < 0.00001) compared to their baseline. Fasting glucose concentrations did not show any significant change. Conclusions Increased post-intervention SCFA is associated with lower fasting insulin, offering a beneficial effect on insulin sensitivity.