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bioRxiv · 10.1101/2025.10.27.684932

Microbial Feast or Famine: dietary carbohydrate composition and gut microbiota metabolic function

Abstract

Diet composition plays a major role in shaping the structure and function of the gut microbiota and influencing host health. While numerous studies have investigated the impact of macronutrient type and quantity on microbiota using in vitro systems, animal models, and human participants, most of these studies focused primarily on microbial-community composition and lacked the functional information that can be gained from transcript-level analyses. In this exploratory analysis, we use metatranscriptomic data to gain a functional perspective on how dietary composition is associated with the gut microbiota and hypothesized implications for host physiology. Data were derived from a tightly controlled, randomized cross-over feeding study conducted in a metabolic ward, where participants consumed two isocaloric and eucaloric diets differing in food processing and fiber content: A Western Diet (WD) limited in fiber, resistant starch, and whole foods and a Microbiome Enhancer Diet (MBD) composed of fiber-rich, whole foods. Our prior findings showed that a WD lead to a resource-limited microbiota enriched in mucin-degrading bacteria that resorted to metabolizing host-derived organic material, while the MBD supported a resource-replete microbiota that primarily metabolized dietary fiber. The objective of this work was to explore these findings more deeply using bioinformatic analyses of metatranscriptomic data. Our analysis showed increased transcription of fiber-degrading enzymes in the MBD and mucin-degrading enzymes in the WD. While in this analysis functional diversity of the gut microbiome was not affected, differences in resistant-starch and fiber content shifted the types of metabolic processes being actively transcribed. The MBD promoted biosynthetic and carbohydrate-fermenting pathways, while the WD was characterized by enzymes for host-glycan and protein degradation. Furthermore, the MBD-supported ecosystem benefits host health via enhanced SCFA production and reduced reliance on host glycan degradation. The WD fostered increased mucin and protein breakdown pathways that yield metabolites that may harm the gut barrier and systemic metabolism.

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BibTeXRIS

Dirks, B., Mohr, A. E., Corbin, K., Carnero, E. A., Smith, S. R., Whisner, C. M., Rittmann, B. E., Krajmalnik-Brown, R.. 2025-10-28. Microbial Feast or Famine: dietary carbohydrate composition and gut microbiota metabolic function. https://doi.org/10.1101/2025.10.27.684932

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