ECCO Grant Study Synopsis: Bahtiyar Yilmaz
Bahtiyar Yilmaz, ECCO Grant Awardee
Identification of gut microbial strains contributing to chronic inflammation in human and mice
© Bahtiyar Yilmaz
Background & aim of research
The relationship between host and microbiota can turn negative, leading to changes in microbial composition and metabolism that result in diseases such as Inflammatory Bowel Disease (IBD). Enteropathogenic strains increase due to the presence of reactive oxygen species in an altered metabolic environment. This study aims to understand how an IBD microbiota carrying an oxidative stress signature adapts over time and how these strains contribute to the disease's trajectory and fluctuations of oxidative stress in the outer mucus layer.
Aim 1: To isolate and characterise the capacity of freshly isolated human small and large intestinal microbial members contributing to oxidative stress.
Aim 2: To colonise germ-free or defined microbiota colonised mice with isolated bacterial strains to test their contributions and resilience to inflammation/oxidative stress in the mouse intestines.
Methodology/experiments that will be used
The study will use ileo- or colostomy samples from patients with IBD and cured colorectal cancer. Outer mucus layer resident gut bacteria will be isolated using different culture media based on their nutritional preferences and stress resistance. The isolated strains will be identified using MALDI-TOF and whole genome sequencing. The study will assess growth dynamics, stress resistance and genomic functions of the strains using different assays and meta-transcriptomics. Selected strains will be introduced into defined microbiota colonised mice to understand their contribution to inflammation.
Anticipated main impact
It is anticipated that this interdisciplinary project will elucidate how the host deals with oxidative stress in the presence of specific intestinal strains, how microbial consortia contribute to oxidative stress production and its potential effect on IBD patients. The study will use gnotobiotic modelling and microbiology to identify bacterial strains with functional importance in generating or diminishing oxidative stress within the real intestinal consortia in vivo. This research goal has clinical relevance and may lead to microbiota manipulation as adjunctive therapy to improve disease course and responsiveness.
April 2023 to December 2024