# Fecal Microbiota Transplant in Veterans with Cirrhosis

> **NIH VA I01** · VA VETERANS ADMINISTRATION HOSPITAL · 2021 · —

## Abstract

Liver cirrhosis is a major cause of morbidity and mortality in Veterans, primarily due to complications such as
ascites and hepatic encephalopathy (HE). HE is linked with a systemic pro-inflammatory milieu propagated by
an impaired intestinal barrier and gut dysbiosis. Despite maximal therapy (lactulose/rifaximin), a significant
proportion of Veterans have HE that continues to recur, which is a major burden on their caregivers and VHA
system. We have recently published a small randomized trial of fecal microbial transplantation (FMT), in this
population, which was safe and prevented total and HE-related hospitalizations. This was associated with
favorable bile acid (BA) and microbial changes which lasted for >1 year with one FMT. A similar small oral
capsule FMT trial is underway at our center with good safety signals. There is also evidence in non-cirrhotic
FMT studies that microbe-free portions can be as effective as full FMT. However, the mechanism of action of
FMT in cirrhosis is needs further investigation.
We hypothesize that “Fecal microbial transplant delivered from the combined oral and rectal route is safe, well-
tolerated and associated with lower hospitalizations, improved modulation of gut microbial composition and
functionality and brain function in patients with hepatic encephalopathy compared to those treated with FMT
from either routes alone or with placebo; this improvement is mediated by microbial products”. We will test this
hypothesis using two translational aims
Aim 1: To determine the effect of dual oral and rectal administration of FMT from a rational donor on
clinical outcomes (hospitalizations, brain function, quality of life) and host-microbiota interactions
(microbial composition and bile acid composition with systemic and intestinal inflammation),
compared to single route of administration and placebo, in cirrhotic patients with HE using a
randomized, phase II clinical trial. Outpatients with recurrent HE (n=100) will be randomized into four groups
(Group 1: Dual oral and rectal FMT, Group 2: Oral FMT and rectal placebo, Group 3: Oral placebo and Rectal
FMT and Group 4: Oral and rectal placebo) and followed for 6 months under an FDA IND double-blind clinical
trial. FMT donors will be selected using machine learning on the basis of beneficial taxa from OpenBiome
donors (collaborator), which will be used for all FMT-assigned subjects. The primary outcome is all-cause
hospitalizations. Patients will undergo baseline evaluation for cirrhosis severity, brain function, intestinal
permeability along with collection of serum and stool and fecal bile acid profile analysis. Patients will be
followed till 6 months for outcomes. We will define the effect of FMT on systemic inflammation, intestinal
permeability, bile acid profile, and its linkage with microbial composition and clinical outcomes between groups.
Aim 2: To determine the effect of human FMT on neuro-inflammation and gut microbial function using
germ-free mice and conv...

## Key facts

- **NIH application ID:** 9931045
- **Project number:** 5I01CX001076-06
- **Recipient organization:** VA VETERANS ADMINISTRATION HOSPITAL
- **Principal Investigator:** Jasmohan S Bajaj
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2015-01-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931045

## Citation

> US National Institutes of Health, RePORTER application 9931045, Fecal Microbiota Transplant in Veterans with Cirrhosis (5I01CX001076-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9931045. Licensed CC0.

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