# A new paradigm of respiration in the human gut Bacteroides

> **NIH NIH R01** · RENSSELAER POLYTECHNIC INSTITUTE · 2020 · $596,165

## Abstract

Project Summary/Abstract
Despite the tremendous amount of data that has been generated over the last decade regarding
the human intestinal microbiota, we still know little about energy generation processes of most
of the abundant members of this ecosystem. This gap in our fundamental knowledge of the gut
microbiota hinders our understanding of how the Bacteroides interact with other community
members, the conditions in the gut environment that contribute to microbial compositional
changes, and how we may appropriately alter the composition of the ecosystem to improve
human health. Bacteroides is the most abundant and stable genus of the human intestinal
microbiota with strains colonizing their hosts for decades. Currently, Bacteroides are predicted
to have a primitive anaerobic respiration pathway that would produce little energy to power
cellular processes. In this application, based on strong supporting data, we will test our premise
that Bacteroides have a more complex respiration pathway that creates a much larger amount
of energy including the direct generation of both H+ and Na+ gradients to power cellular
processes. Central to this new paradigm is our prediction that Bacteroides have a complete
aerobic respiration pathway that allows them to utilize oxygen at the mucus layer of the colonic
epithelium, which we predict significantly contributes to their fitness in the gut. In addition, we
will test our hypothesis that aerobic respiration by the Bacteroides has community-wide effects,
significantly contributing to the low oxygen environment of the colon, allowing oxygen intolerant
members to colonize the gut, especially near the mucus layer. The objectives of this application
will be addressed in three aims, taking advantage of the diverse strengths of three co-PIs. In
Aim 1, we will use genetics, functional assays and biochemistry to completely elucidate both the
aerobic and anaerobic pathways of Bacteroides. In Aim 2, we will focus on the ion gradients
that the respiration pathway creates and the cellular processes that they energize. In Aim 3, we
will use gnotobiotic mouse models to test which enzymes of the respiration pathway are critical
for in vivo fitness, the role of aerobic respiration in conferring a fitness advantage to the
Bacteroides, and the community wide effects of aerobic respiration on the gut microbiota and
colonization of enteric pathogens. We predict this project will reveal new paradigms that will
alter our thinking about Bacteroides, their ecological effects in the gut microbiota, and the
conventional wisdom that these bacteria are strict anaerobes.

## Key facts

- **NIH application ID:** 9974458
- **Project number:** 5R01AI132580-04
- **Recipient organization:** RENSSELAER POLYTECHNIC INSTITUTE
- **Principal Investigator:** Blanca Barquera
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $596,165
- **Award type:** 5
- **Project period:** 2017-08-18 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974458

## Citation

> US National Institutes of Health, RePORTER application 9974458, A new paradigm of respiration in the human gut Bacteroides (5R01AI132580-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9974458. Licensed CC0.

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