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Designing fiber-gut microbiome interactions with active learning.

Journal articles  - Journal Article
Connors, BM; Thompson, J; Gangan, MS; Quinn-Bohmann, N; Gibbons, SM; Grant, J; Castellanos-Sanchez, A; McCann, JR; Rawls, JF; Venturelli, OS
Published in: Nat Chem Biol
August 2026

Identifying synergies between dietary fibers and beneficial bacteria holds promise for precision interventions that optimize gut health, yet these interactions remain largely unexplored. Here we integrate machine learning, Bayesian optimization and high-throughput community construction to investigate how dietary fibers shape health-relevant functions of human gut microbial communities. To efficiently navigate the landscape of fiber-microbiome interactions, we implemented a design-test-learn cycle to identify fiber-species combinations that maximize a multiobjective function capturing beneficial community properties. Our model-guided approach revealed a highly butyrogenic and robust ecological motif characterized by the copresence of inulin, Bacteroides uniformis and Anaerostipes caccae and a higher-order interaction with Prevotella copri. Human fecal communities invaded with model-designed species-fiber combinations displayed predictable gut-beneficial outputs. In sum, we demonstrate a framework for designing synthetic microbial communities with desired functions in response to key nutrients.

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Published In

Nat Chem Biol

DOI

EISSN

1552-4469

Publication Date

August 2026

Volume

22

Issue

8

Start / End Page

1286 / 1298

Location

United States

Related Subject Headings

  • Prevotella
  • Machine Learning
  • Inulin
  • Humans
  • Gastrointestinal Microbiome
  • Feces
  • Dietary Fiber
  • Biochemistry & Molecular Biology
  • Bayes Theorem
  • Bacteroides
 

Citation

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Connors, B. M., Thompson, J., Gangan, M. S., Quinn-Bohmann, N., Gibbons, S. M., Grant, J., … Venturelli, O. S. (2026). Designing fiber-gut microbiome interactions with active learning. Nat Chem Biol, 22(8), 1286–1298. https://doi.org/10.1038/s41589-026-02272-4
Connors, Bryce M., Jaron Thompson, Manasi Subhash Gangan, Nick Quinn-Bohmann, Sean M. Gibbons, Job Grant, Alejandro Castellanos-Sanchez, Jessica R. McCann, John F. Rawls, and Ophelia S. Venturelli. “Designing fiber-gut microbiome interactions with active learning.Nat Chem Biol 22, no. 8 (August 2026): 1286–98. https://doi.org/10.1038/s41589-026-02272-4.
Connors BM, Thompson J, Gangan MS, Quinn-Bohmann N, Gibbons SM, Grant J, et al. Designing fiber-gut microbiome interactions with active learning. Nat Chem Biol. 2026 Aug;22(8):1286–98.
Connors, Bryce M., et al. “Designing fiber-gut microbiome interactions with active learning.Nat Chem Biol, vol. 22, no. 8, Aug. 2026, pp. 1286–98. Pubmed, doi:10.1038/s41589-026-02272-4.
Connors BM, Thompson J, Gangan MS, Quinn-Bohmann N, Gibbons SM, Grant J, Castellanos-Sanchez A, McCann JR, Rawls JF, Venturelli OS. Designing fiber-gut microbiome interactions with active learning. Nat Chem Biol. 2026 Aug;22(8):1286–1298.

Published In

Nat Chem Biol

DOI

EISSN

1552-4469

Publication Date

August 2026

Volume

22

Issue

8

Start / End Page

1286 / 1298

Location

United States

Related Subject Headings

  • Prevotella
  • Machine Learning
  • Inulin
  • Humans
  • Gastrointestinal Microbiome
  • Feces
  • Dietary Fiber
  • Biochemistry & Molecular Biology
  • Bayes Theorem
  • Bacteroides