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New model defines essential gut microbiome components for human health

Researchers have developed a novel approach to identifying the critical set of gut microbes necessary for human health, offering fresh insights into how microbiome imbalances may contribute to chronic diseases.

Understanding bacterial communities
The study represents a significant departure from conventional microbiome analysis methods, which typically define core microbiota based on commonly shared taxonomic units within human populations. These traditional approaches have been limited by their inability to differentiate between beneficial and harmful strains within the same species.

The new methodology employs high-quality genomes assembled directly from metagenomic sequencing datasets, with each genome receiving a universal unique identifier to track its ecological behaviour. This approach enables researchers to include previously unclassifiable novel bacteria whilst maintaining high-resolution analysis.

Competing bacterial guilds
Central to the new model is the identification of two distinct bacterial groups: the Foundation Guild and the Pathobiont Guild. These communities exist in a dynamic balance that appears crucial for maintaining optimal health.

The Foundation Guild serves as a cornerstone for gut microbiome stability, primarily through its role in dietary fibre degradation and the production of short-chain fatty acids (SCFAs), particularly butyrate. These metabolites are essential for maintaining the gut barrier, reducing inflammation, and providing energy to colonic cells.

In contrast, the Pathobiont Guild, whilst necessary in small quantities for immune system education, can potentially trigger disease processes if it becomes dominant. This delicate balance between the two guilds appears to be a key determinant of gut health.

Clinical implications
Professor Liping Zhao, the Eveleigh-Fenton Chair of Applied Microbiology at Rutgers University, explained: “Our research identifies the bacteria in the gut that stay connected, no matter what challenges the body faces, such as dietary changes or illness. By focusing on these resilient and interconnected bacteria, we’ve developed a new method for pinpointing the microbes that are most crucial for maintaining our health.”

The research suggests that when the Foundation Guild maintains dominance, gut health is preserved. However, if the balance shifts towards the Pathobiont Guild, dysbiosis may occur, potentially exacerbating various chronic conditions including inflammatory bowel disease, metabolic disorders, and certain cancers.

“Our model not only helps us identify these core bacterial guilds but also shows how they can be nurtured to maintain their dominance,” Zhao added. “This opens up new possibilities for personalized nutrition and targeted therapies that can restore balance in the gut microbiome.”

The researchers are now planning clinical trials to refine personalised therapeutic approaches aimed at restoring and maintaining Foundation Guild dominance in patients with severe dysbiosis. The model’s ability to predict personalised responses to immunotherapy across four different diseases suggests potential applications beyond gut health.

The study involved collaboration between experts from Rutgers, Shanghai Jiao Tong University, Tufts University Medical School, and other institutions, with financial support from various organisations including the New Jersey Institute for Food, Nutrition, and Health at Rutgers and the Canadian Institute for Advanced Research.

Reference:

  1. Zhao, L., et al. (2024). A core microbiome signature as an indicator of health. Cell. DOI: https://doi.org/10.1016/j.cell.2024.09.019
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