# Novel mechanism in microbiota-brain communication: the role of the hepatoportal region

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2022 · $382,500

## Abstract

PROJECT SUMMARY
Signals from peripheral tissues play an important role in aligning sleep-wake activity with the metabolic, nutri-
tional and immune status of the organism. The intestinal microbiota is an essential source of such signals
through the production of bacterial metabolites, e.g., short-chain fatty acids (SCFAs), and the release of bacterial
cell wall components, lipopolysaccharide (LPS) and peptidoglycans. The long-term objective is to identify
mechanisms of microbiota-brain communications and its relevance to sleep regulation. The objective of the
present proposal is to investigate the newly discovered sleep-promoting viscerosensory mechanism in the
hepatoportal region. Activation of hepatoportal sensors by SCFAs and bacterial cell wall products is a potent
sleep-promoting signal. The central hypothesis is that bacterial products, such as LPS that translocate from the
intestinal lumen to the liver via the portal vein, activate hepatic macrophages. Macrophages, in turn, secrete
prostaglandins locally, which activate the sensory neurons of the hepatic vagus. Vagus carries somnogenic
signal to the nucleus tractus solitarius, a component of brain stem sleep circuits. In three specific aims, we will
1) determine the role of hepatic macrophages in LPS-induced sleep in macrophage-depleted rats, 2) determine
the contribution of hepatic prostaglandin E2 in sleep signaling 3) determine the contribution of hepatic vagal
afferents in hepatoportal sleep induction. The concept of microbiota-gut-brain axis is viewed as a major paradigm
shift in neuroscience. Changes in the composition of microbiota as well as increased translocation of microbial
products to the systemic circulation are related to pathological conditions, including disorders of the central
nervous system. Identifying the role of bacterial products in sleep regulation is important because the gut flora
is susceptible to changes in diet, environment, food additives and antibiotic treatment, which could lead to altered
sleep, but it can also provide an easily accessible target for translational research to improve sleep.

## Key facts

- **NIH application ID:** 10382242
- **Project number:** 5R01HL151853-03
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** LEVENTE KAPAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2020-04-05 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10382242

## Citation

> US National Institutes of Health, RePORTER application 10382242, Novel mechanism in microbiota-brain communication: the role of the hepatoportal region (5R01HL151853-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10382242. Licensed CC0.

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