# Effect of Gut Microbiome Dysbiosis in the Pathobiology of Multiple Sclerosis

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2021 · —

## Abstract

Despite the association between gut microbiota and multiple sclerosis (MS) being increasingly
appreciated, the mechanism through which gut bacteria and their metabolites modulate disease in MS is poorly
understood. We and others have shown a link between perturbations in the gut microbiota in MS patients. Gut
dysbiosis, a qualitative alteration in healthy gut microbiota is characterized by an increased abundance of
inflammation-promoting bacteria (pathobiont) and depletion of beneficial bacteria (symbionts). As MS is an
inflammatory disease, an increase in pathobionts and/or decrease in symbionts might promote pro-
inflammatory environment influencing disease development and progression. Pathobionts are known to
promote pro-inflammatory environment by causing increased intestinal permeability which leads to leaky gut
syndrome by allowing leakage of bacterial products (LPS and other inflammatory mediators) into the systemic
circulation. Increased systemic levels of gut permeability linked inflammatory mediators (GPLIMS) can induce
inflammation through canonical and non-canonical pathways including suppression of specialized pro-resolving
mediators (SPMs), a set of naturally occurring molecules produced within our body to dampen inflammation. It
is important to highlight that gut microbiota help in production of SPMs from diet. Alteration in the ratio of
GPLIMs and SPMs could modulate the disease course and clinical outcomes. Additionally, depletion of
symbionts responsible for maintaining immune homeostasis can also promote a pro-inflammatory environment
by tilting balance between pro- and anti-inflammatory immune responses towards pro-inflammatory response.
We have earlier reported that multiple gut bacteria associated with metabolism of dietary phytoestrogens into
Equol is depleted in MS patients, thus highlighting a critical role of phytoestrogen metabolism in mediating
beneficial effect of gut microbiome. Although, an inverse correlation between leaky gut and Equol had been
reported in some inflammatory diseases, its role in the pathobiology of MS is unknown.
 There is a knowledge gap in our understanding about the mechanism(s) of gut dysbiosis in MS
patients. To this end, our proposal is significant and critical to fill this void by determining the relative
contributions of pathobionts (leaky gut syndrome) and symbionts (phytoestrogen metabolism) in MS. Our long-
term goal is to determine mechanism(s) through which gut bacteria and their metabolites influence protection
from or predisposition/progression to MS. We hypothesize that gut dysbiosis promotes MS through
enrichment of pathobionts which leads to leaky gut syndrome in addition to depletion of beneficial Equol
producing gut bacteria. We, therefore, propose to determine the significance of leaky gut and Equol producing
gut bacteria in the pathogenesis of MS in the following three aims. In the first aim, we will test the hypothesis
that gut dysbiosis in MS patients results in leaky gut a...

## Key facts

- **NIH application ID:** 10114713
- **Project number:** 1I01CX002212-01
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** Ashutosh Kumar Mangalam
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114713

## Citation

> US National Institutes of Health, RePORTER application 10114713, Effect of Gut Microbiome Dysbiosis in the Pathobiology of Multiple Sclerosis (1I01CX002212-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10114713. Licensed CC0.

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