Maternal supplementation of resistant starch type 4 improves energy balance, reprograms gut microbiota and protects offspring against diet-induced obesity

Published: 12 December 2025| Version 1 | DOI: 10.17632/xptxhtzfzm.1
Contributors:
Souvik Patra, Yesica Botero, Gizem Levent, Prasanth Chelikani

Description

Our central hypothesis was that maternal RS-4 supplementation reshapes the maternal gut microbiota during gestation and lactation, and that these shifts contribute to programming offspring microbiota structure and obesity risk. To test this, we profiled maternal fecal microbiota on gestational days 8 and 14, and cecal microbiota in dams and offspring at weaning and adulthood using 16S rRNA sequencing. In mothers, RS-4 produced a distinct microbial signature characterized by increased Bacteroidota and reduced Firmicutes, alongside stable alpha-diversity over time, contrasting with the high-fat diet (HFD), which showed a pronounced decline in richness and evenness as gestation progressed. Beta-diversity analyses revealed that RS-4 generated community structures that were significantly different from both LFD and HFD, indicating robust microbial remodeling. In the cecum, RS-4 dams again exhibited higher Bacteroidaceae abundance and reduced Lachnospiraceae relative to HFD, demonstrating consistent fiber-driven shifts across gut compartments. Offspring microbiota were markedly different from their dams, but both prenatal diet and lactation environment shaped their microbial communities. Internal (biological) offspring from RS-4 mothers displayed greater phylogenetic diversity than their dams and distinct community structures compared with LFD and HFD groups. Cross-fostering revealed strong lactational imprinting: pups nursed by HFD dams—regardless of birth mother, developed microbial communities that diverged significantly from their biological siblings. Conversely, RS-4 foster pups maintained similar richness and evenness to RS-4 internal controls, although community composition still shifted, indicating that RS-4 primarily influences lineage selection rather than overall diversity. Collectively, these findings demonstrate that RS-4 promotes a stable, saccharolytic maternal microbiota and partially transmits this ecological advantage to offspring, while lactation remains a dominant window through which microbiota structure and thus metabolic programming is determined.

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Institutions

  • Texas Tech University

Categories

Metagenomics, Gut Microbiota, Prebiotics

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