Short-chain fatty acids and insulin sensitivity: a systematic review and meta-analysis

Abstract

Context: There is substantial evidence that reduced short-chain fatty acids (SCFAs) in the gut are associated with obesity and type 2 diabetes, although findings from clinical interventions that can increase SCFAs are inconsistent.

Objective: This systematic review and meta-analysis aimed to assess the effect of SCFA interventions on fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR).

Data sources: Relevant articles published up to July 28, 2022, were extracted from PubMed and Embase using the MeSH (Medical Subject Headings) terms of the defined keywords [(short-chain fatty acids) AND (obesity OR diabetes OR insulin sensitivity)] and their synonyms. Data analyses were performed independently by two researchers who used the Cochrane meta-analysis checklist and the PRISMA guidelines.

Data extraction: Clinical studies and trials that measured SCFAs and reported glucose homeostasis parameters were included in the analysis. Standardized mean differences (SMDs) with 95%CIs 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 randomized and crossover studies.

Data analysis: In total, 6040 nonduplicate studies were identified, 23 of which met the defined criteria, reported fasting insulin, fasting glucose, or HOMA-IR values, and reported change in SCFA concentrations post intervention. Meta-analyses of these studies indicated that fasting insulin concentrations were significantly reduced (overall effect: SMD = -0.15; 95%CI = -0.29 to -0.01, P = 0.04) in treatment groups, relative to placebo groups, at the end of the intervention. Studies with a confirmed increase in SCFAs at the end of intervention also had a significant effect on lowering fasting insulin (P = 0.008). Elevated levels of SCFAs, compared with baseline levels, were associated with beneficial effects on HOMA-IR (P < 0.00001). There was no significant change in fasting glucose concentrations.

Conclusion: Increased postintervention levels of SCFAs are associated with lower fasting insulin concentrations, offering a beneficial effect on insulin sensitivity.

Systematic review registration: PROSPERO registration number CRD42021257248.

Keywords: HOMA-IR; acetate; butyrate; insulin sensitivity; propionate; short-chain fatty acids; type 2 diabetes.

Figure 1

Flow diagram of the literature search process.

Figure 2

Fasting insulin concentrations from each study were compared between placebo group and treatment group at the end of the intervention period. Data are presented as the standardized mean difference (SMD) in fasting insulin (µU/mL) and have been separated into two subgroups: one with evidence of an increase in short-chain fatty acids (SCFAs) concentration(s) post intervention, and the other without any change in SCFAs post intervention. The type of intervention (M, meal/mixed; C3, propionate) is noted at the end of each study. Abbreviation: IV, inverse variance.

Figure 3

Fasting glucose concentrations from each study were compared between placebo group vs treatment group at the end of the intervention period. Data are presented as the standardized mean difference (SMD) in fasting glucose (mmol/L) and have been separated into two subgroups: one with evidence of an increase in short-chain fatty acids (SCFAs) concentration(s) post intervention, and the other without any change in SCFAs post intervention. The type of intervention (M, meal/mixed; C3, propionate) is noted at the end of each study. Abbreviation: IV, inverse variance.

Figure 4

Homeostatic model assessment of insulin resistance (HOMA-IR) values were compared between placebo group and treatment group at the end of the intervention period. Data are presented as the standardized mean difference (SMD) in HOMA-IR and have been separated into two subgroups: one with evidence of an increase in short-chain fatty acids (SCFAs) concentration(s) post intervention, and the other without any change in SCFAs post intervention. The type of intervention (M, meal/mixed; C3, propionate) is noted at the end of each study. Abbreviation: IV, inverse variance.

Figure 5

Fasting insulin concentrations at baseline and endpoint (end of intervention) from each study in the treatment group. Data are presented as the standardized mean difference (SMD) in fasting insulin (µU/mL) and have been separated into two subgroups: one with evidence of an increase in short-chain fatty acids (SCFAs) concentration(s) post intervention, and the other without any change in SCFAs post intervention. The type of intervention (M, meal/mixed; C3, propionate; C2, acetate) is noted at the end of each study. Abbreviation: IV, inverse variance.

Figure 6

Fasting glucose concentrations at baseline and endpoint (end of intervention) from each study in the treatment group. Data are presented as the standardized mean difference (SMD) in fasting insulin (mmol/L) and have been separated into two subgroups: one with evidence of an increase in short-chain fatty acids (SCFAs) concentration(s) post intervention, and the other without any change in SCFAs post intervention. The type of intervention (M, meal/mixed; C3, propionate; C2, acetate) is noted at the end of each study. Abbreviation: IV, inverse variance.

Figure 7

Homeostatic model assessment of insulin resistance (HOMA-IR) values at baseline and endpoint (end of intervention) from available studies in the treatment group. Data are presented as the standardized mean difference (SMD) in HOMA-IR and have been separated into two subgroups: one with evidence of an increase in short-chain fatty acids (SCFAs) concentration(s) post intervention, and the other without any change in SCFAs post intervention. The type of intervention (M, meal/mixed; C3, propionate) is noted at the end of each study. Abbreviation: IV, inverse variance.