Activity-based protein profiling identifies alternating activation of enzymes involved in the bifidobacterium shunt pathway or mucin degradation in the gut microbiome response to soluble dietary fiber

Journal Article · Wed Jul 20 00:00:00 EDT 2022 · npj Biofilms and Microbiomes

DOI:https://doi.org/10.1038/s41522-022-00313-z· OSTI ID:1881474

Killinger, Bryan J. ^[1]; Whidbey, Christopher-Mychael ^[2]; Sadler, Natalie C. ^[3]; DeLeon, Adrian J. ^[3]; Munoz, Nathalie ^[3]; Kim, Young-Mo ^[3]; Wright, Aaron T. ^[1]

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1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Washington State Univ., Pullman, WA (United States)
2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Seattle Univ., WA (United States)
3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

While deprivation of dietary fiber has been associated with adverse health outcomes, investigations concerning the effect of dietary fiber on the gut microbiome have been largely limited to compositional sequence-based analyses or utilize a defined microbiota not native to the host. To extend understanding of the microbiome’s functional response to dietary fiber deprivation beyond correlative evidence from sequence-based analyses, approaches capable of measuring functional enzymatic activity are needed. In this study, we use an activity-based protein profiling (ABPP) approach to identify sugar metabolizing and transport proteins in native mouse gut microbiomes that respond with differential activity to the deprivation or supplementation of the soluble dietary fibers inulin and pectin. We found that the microbiome of mice subjected to a high fiber diet high in soluble fiber had increased functional activity of multiple proteins, including glycoside hydrolases, polysaccharide lyases, and sugar transport proteins from diverse taxa. The results point to an increase in activity of the Bifidobacterium shunt metabolic pathway in the microbiome of mice fed high fiber diets. In those subjected to a low fiber diet, we identified a shift from the degradation of dietary fibers to that of gut mucins, in particular by the recently isolated taxon “Musculibacterium intestinale”, which experienced dramatic growth in response to fiber deprivation. When combined with metabolomics and shotgun metagenomics analyses, our findings provide a functional investigation of dietary fiber metabolism in the gut microbiome and demonstrates the power of a combined ABPP-multiomics approach for characterizing the response of the gut microbiome to perturbations.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
• Sponsoring Organization: National Institutes of Health (NIH); USDOE Laboratory Directed Research and Development (LDRD) Program
• Grant/Contract Number: AC05-76RL01830
• OSTI ID: 1881474
• Report Number(s): PNNL-SA-153236
• Journal Information: npj Biofilms and Microbiomes, Journal Name: npj Biofilms and Microbiomes Journal Issue: 1 Vol. 8; ISSN 2055-5008
• Publisher: Springer Nature
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES