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Updated: May 9, 2026
An In Vitro Batch-culture Model to Estimate the Effects of Interventional Regimens on Human Fecal Microbiota
Published on: July 31, 2019
Gut microbiota responses to isocaloric macronutrient modulation in tissue-specific insulin resistance: a secondary
Kelly M Jardon1, Alexander Umanets2, Koen Venema2
1TiFN, Wageningen, The Netherlands; Department of Human Biology, NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands.
Background:
Precision nutrition strategies can be effective in optimizing health outcomes. We previously showed that dietary macronutrient modulation targeting tissue-specific insulin resistance (IR) phenotypes induced pronounced improvements in cardiometabolic health. It remains unclear whether these improvements may partially be explained by gut microbiota-related mechanisms.
Objectives:
We investigated whether 12-wk high monounsaturated fatty acid (HMUFA) and low-fat, high-protein, high-fiber diets (LFHP) impact gut microbiota composition and functionality in people with predominant muscle IR (MIR) compared with liver IR (LIR) in relation to cardiometabolic health improvements.
Methods:
This 2-center, randomized, double-blind, dietary intervention trial included 179 individuals with LIR or MIR [40‒75 y, body mass index (in kg/m2) 25‒40], who followed either a 12-wk isocaloric HMUFA or LFHP diet. A 7-point oral glucose tolerance test was performed to determine tissue-specific IR and cardiometabolic risk factors. Fecal microbiota composition was profiled using 16S ribosomal ribonucleic acid amplicon sequencing (V3‒V4 region), and GLP-1 and gut microbial products were determined in plasma and feces.
Results:
The HMUFA diet induced significant shifts in overall gut microbial composition (P < 0.05) and short-chain fatty acid-producing bacteria (q < 0.05) in the LIR phenotype, but not in MIR. The LFHP diet induced only modest changes in gut microbiota features. We found phenotype-specific correlations between specific baseline taxa abundance and change in metabolic outcomes (MIR-HMUFA: Barnesiella-ΔMISI (Spearman ρ = 0.45, P < 0.001); LIR-HMUFA: Sutterella-Δplasma-C-reactive protein (Spearman ρ = 0.57, P = 0.0001) and a Rhodospirillales genus-Δhomeostasis model assessment of insulin resistance (Spearman ρ = ‒0.58, P < 0.001).
Conclusions:
Individuals with predominant LIR seem more prone to diet-induced gut microbiota-related improvements in cardiometabolic health than those with MIR, highlighting the importance of understanding heterogeneity in IR. Our findings support a role for the gut microbiota in precision nutrition targeting tissue-specific IR.
Clinicaltrials:
gov registration: This is a secondary analysis of the PERSonalized glucose Optimization through Nutritional intervention (PERSON) randomized trial.
Registration Number:
NCT03708419, https://clinicaltrials.gov/study/NCT03708419.
