# Impact of Circadian-Microbiome Interaction on the Gut-Pancreas Axis in Aging

> **NIH NIH U01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $671,922

## Abstract

Abstract
 Low grade systemic inflammation (or inflammaging) associates with many age-associated diseases.
Among the mechanisms that incite inflammaging, damage to the intestinal barrier is likely among the most
important. As a common feature of aging, several studies have indicated a close connection between intestinal
barrier dysfunction, changes in the gut microbiota and chronic inflammation along with systemic multi-organ
injuries. One such organ is the pancreas where barrier impairment is known to contribute to several age-
associated disorders, including impaired insulin secretion and cancer. Despite these connections, why the
intestinal barrier becomes dysfunctional as we age, what drives the changes in microbiome with aging and how
these factors affect the quality of aging are unknown. Answers to these questions will help us identify
mechanisms of healthy aging which is a critical knowledge gain towards increasing quality of life in our aging
population.
 Studies from our group suggest that both the intestinal barrier and microbiome can change in response
to exposure to lifestyle factors (e.g., diet, eating time), that are important modifiable determinant of healthy aging.
In fact, changes in our lifestyle are likely why “aging”-related pathologies are on the rise. Of the several lifestyle
factors that may affect aging, disruption of circadian rhythms that govern a wide spectrum of host physiology is
quite common in our modern society. We and others have shown that disruptions of circadian rhythms negatively
affect intestinal microbiota and barrier function, leading to intestinal and extra-intestinal injuries including in
pancreas. Here we will study the impact of circadian disruptions on the gut-pancreas axis in aging through
microbial signaling. In Aim 1, we will study how food timing (as a proxy for peripheral circadian disruption) affects
intestinal driven inflammation and pancreas aging in mice. We will determine novel microbiome-host rhythms
that are under circadian cues and are connected to the gut-pancreas aging processes. Human studies in Aim 2
will aid in establishing the causal role of microbial signaling in mediating the effect of the host circadian disruption
on the gut-pancreas physiology. Our work will provide critical insights into targetable gut-centric anti-aging
mechanisms that could be considered for future trials as well as for developing prophylactic therapies.

## Key facts

- **NIH application ID:** 10851568
- **Project number:** 1U01AG086145-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Faraz Bishehsari
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $671,922
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851568

## Citation

> US National Institutes of Health, RePORTER application 10851568, Impact of Circadian-Microbiome Interaction on the Gut-Pancreas Axis in Aging (1U01AG086145-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10851568. Licensed CC0.

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