# Host-microbe interactions: Harnessing co-evolution to treat disease

> **NIH NIH DP1** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2020 · $1,346,800

## Abstract

Abstract
A new perspective for treating disease. There is a disconnect between our methods for treating diseases
and our understanding of the mechanisms that keep us healthy; this needs to change. The past fifty years of
biological research have done an excellent job of understanding disease pathogenesis by reducing the
organism to its component parts, in order to understand the intricate details of how dysfunction of these parts
leads to disease. A significant limitation to this approach, however, is that physiologies do not exist in
isolation; when one system becomes dysfunctional, the whole body is affected. A second issue that
complicates this approach is that current methods for treating disease primarily involve blocking pathogenic
responses rather than inducing pathways that work to maintain health. The reason for this is two-fold: 1)
scientists study disease, not health, and therefore do not understand the mechanisms that promote health;
and 2) It is commonly assumed that blocking a pathogenic response will bring the patient back to a healthy
state, which is not necessarily true. Therefore, rather than asking how we should treat disease, the question
that should be asked is, “How is health maintained?”
 To understand and ultimately manipulate the complex multi-directional interactions that occur between all
of our physiologies, a novel approach is proposed in this application. This approach is based on
understanding that the body and its resident microbiota have co-evolved to rely on communication between all
physiologies in order to maintain proper physiological function. The overall hypothesis of this proposal is that
health is an active process that includes the induction of physiological mechanisms coordinated by microbes.
By understanding the physiological mechanisms our bodies encode and how microbes coordinate these
processes to maintain health, treatments that work to extend health-span and lifespan by overriding
physiological decline can be developed, enabling patients to stay healthy despite infection. This application
proposes a new paradigm for studying disease, where whole animal models, evolutionary principles and host-
microbe interactions are used to define the properties and fundamental principles governing health. The work
resulting from this application will establish a new conceptual framework and approaches in which to
mechanistically understand what it means to be healthy and how this can be applied to treat diseases.

## Key facts

- **NIH application ID:** 9977129
- **Project number:** 5DP1AI144249-03
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Janelle S Ayres
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,346,800
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977129

## Citation

> US National Institutes of Health, RePORTER application 9977129, Host-microbe interactions: Harnessing co-evolution to treat disease (5DP1AI144249-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977129. Licensed CC0.

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