Short-chain fatty acids as anti-inflammatory agents in overweight and obesity: a systematic review and meta-analysis.

Nutrition reviews

Sep 2021

DOI: 10.1093/nutrit/nuab059

Citations:40

Influential Citations:1

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Participants were adults who were overweight or obese; some studies included individuals with type 2 diabetes, prediabetes or insulin resistance, metabolic syndrome, nonalcoholic fatty liver disease, or bariatric status; study designs among humans included randomized controlled trials (27, with 10 crossover trials), 1 intervention study, and 1 secondary analysis of an RCT; other included designs encompassed quasi-experimental, cohort, case-control, before-and-after, and cross-sectional studies.

Intervention

Regimens varied across studies; SCFAs (sodium acetate and sodium butyrate) were delivered orally, intravenously, by infusion, or enema; Prebiotics included resistant starch, inulin, oligofructose, galacto-oligosaccharides, fructo-oligosaccharides, arabinoxylan-oligosaccharides, isomalto-oligosaccharides, psyllium, guar gum, acorn- and sago-derived prebiotics, and apple-derived pectin; durations ranged from 1 hour to 36 weeks. Minimum effective prebiotic dose for reducing plasma LPS observed was 6 g/day galacto-oligosaccharide.

Results

Prebiotic interventions in overweight/obese humans significantly reduced circulating high-sensitivity C-reactive protein (hs-CRP) and lipopolysaccharide (LPS); randomized meta-analysis showed hs-CRP decreased (SMD −0.83; 95% CI −1.56 to −0.11; I2 = 86%; P = 0.02) and LPS decreased (SMD −1.20; 95% CI −1.89 to −0.51; I2 = 87%; P = 0.0006). In animals, prebiotics lowered TNF-α (SMD −0.63; 95% CI −1.19 to −0.07; P = 0.03). For SCFAs in humans, 3 of 4 interventions reduced a systemic inflammatory biomarker. The evidence supports SCFAs and prebiotics as novel aids to reduce obesity-related systemic inflammation, though substantial heterogeneity across studies limits precise dosing/form recommendations; more research is needed to identify optimal regimens and mechanisms.

Limitations

Heterogeneity across supplement types, doses, durations, and outcomes; small sample sizes for some analyses; variable study designs; background diet not consistently controlled; exclusion of non-English studies; animal data may involve nontranslatable high-fiber doses; limited data on plasma SCFA measurement as a proxy for production.

Abstract

CONTEXT Short-chain fatty acids (SCFAs) derived from microbial fermentation of prebiotic soluble fibers are noted for their anti-inflammatory benefits against obese systemic inflammation. OBJECTIVE A systematic review and meta-analysis were undertaken to investigate the effect of SCFAs and prebiotic interventions on systemic inflammation in obesity. DATA SOURCES Relevant studies from 1947 to August 2019 were collected from the Cumulative Index to Nursing and Allied Health Literature, Embase, Medline, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. STUDY SELECTION Of 61 included studies, 29 were of humans and 32 of animals. DATA EXTRACTION Methodological quality of studies was assessed using the critical appraisal checklist of the Academy of Nutrition and Dietetics. Data pertaining to population, intervention type and duration, and markers of systemic inflammation were extracted from included studies. RESULTS Of 29 included human studies, 3 of 4 SCFA interventions and 11 of 25 prebiotic interventions resulted in a significant decrease in ≥1 biomarker of systemic inflammation. Of 32 included animal studies, 10 of 11 SCFA interventions and 18 of 21 prebiotic interventions resulted in a significant reduction of ≥1 biomarker of systemic inflammation. Meta-analysis revealed that prebiotics in humans reduced levels of plasma high-sensitivity C-reactive protein (standard mean difference [SMD], -0.83; 95%CI: -1.56 to -0.11; I2: 86%; P = 0.02) and plasma lipopolysaccharide (SMD, -1.20; 95%CI: -1.89 to -0.51; I2: 87%; P = 0.0006), and reduced TNF-α levels in animals (SMD, -0.63; 95%CI: -1.19 to -0.07; P = 0.03). Heterogeneity among supplement types, duration, and dose across studies was significant. CONCLUSION Evidence from this review and meta-analysis supports the use of SCFAs and prebiotics as novel aids in treatment of obese systemic inflammation. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42020148529. show less