# The role of the gut microbiome in susceptibility to Mycobacterium tuberculosis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $187,120

## Abstract

PROJECT SUMMARY
Tuberculosis (TB) is a deadly infectious disease that kills over 1.7 million people per year. The
majority of individuals are able to control Mycobacterium tuberculosis (Mtb) infection, yet others are
extremely vulnerable. Life-threatening disease symptoms, including extreme weight loss or cachexia,
are also heterogenous across individuals. Immunocompromised people are particularly susceptible to
TB, and less extreme variations in immune system function may also contribute to susceptibility. The
mammalian gut microbiome is a complex community of microbes with extreme variation across
individuals. Gut microbiome composition impacts immune function and susceptibility to a variety of
pathogens. Our pilot data suggests that genetically identical mice with distinct gut microbiomes have
altered ability to control Mtb infection. In this proposal we will interrogate the role of the microbiome in
Mtb control and cachexia. First, we will expand our comparison of mice from different housing
conditions to determine the extent of variation in Mtb burden. To confirm the role of the microbiome in
Mtb infection control, we will transplant fecal microbiomes of interest into germ-free mice and repeat
Mtb infection. We will also profile the immune response to infection in each case. Second, we will
explore the role of the gut microbiome in mediating TB associated cachexia by measuring microbial
and metabolic changes over time in genetically identical mice with diverse microbiomes. In follow up,
we will isolate gut bacteria of interest from these microbiomes to investigate how microbial
metabolism may impact immune function. This proposal will open up a new area of research to probe
the role of the gut microbiome in the pathogenesis of TB. This research has the potential to identify
new microbial and host directed therapeutic targets for TB prophylaxis and treatment.

## Key facts

- **NIH application ID:** 10647554
- **Project number:** 1R21AI176295-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Ashley Robin Wolf
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $187,120
- **Award type:** 1
- **Project period:** 2023-07-03 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10647554

## Citation

> US National Institutes of Health, RePORTER application 10647554, The role of the gut microbiome in susceptibility to Mycobacterium tuberculosis (1R21AI176295-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10647554. Licensed CC0.

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