High-Molecular-Weight Pectin Alleviates Fiber-Free High-Fat Diet-Induced Obesity by Regulating the Colonic Microenvironment and Spatial Microbiota Distribution.

Obesity is increasingly linked to high-fat, fiber-deficient dietary patterns that disturb the intestinal microenvironment and gut microbiota. Here, we tested whether pectin molecular weight determines efficacy by comparing high-molecular-weight apple pectin (HAP) with low-molecular-weight pectin (LAP) in a fiber-free, high-fat-diet (FF-HFD) mouse model. In young C57BL/6J mice, HAP more strongly improved body weight gain, glucose homeostasis, and lipid abnormalities than LAP, accompanied by enhanced barrier markers, reduced systemic inflammation, lower brain LPS, and partial normalization of fecal microbiota and fermentation outputs. Segment-resolved profiling further showed that HAP partially restored proximal-distal luminal microbiota patterns disrupted by FF-HFD. In an aged cohort, HAP also alleviated obesity-associated hepatic steatosis and behavioral deficits. These findings highlight molecular weight as a practical lever to optimize pectin-based interventions under fiber-deficient, high-fat feeding.