In a groundbreaking study published in Cell, researchers at Rutgers University-New Brunswick, in collaboration with international partners, have unveiled a revolutionary method for pinpointing the essential set of gut microbes crucial for human health. This discovery opens up new avenues for precision nutrition and personalized therapies aimed at managing chronic diseases linked to imbalances in the gut microbiome, such as diabetes, inflammatory bowel disease, and cancer.
The core microbiome, a collection of microbes within the digestive tract, plays a pivotal role in sustaining essential functions like digestion, immune defense, and mental well-being. When there is a decrease or loss of the core microbiome, a condition referred to as dysbiosis occurs, characterized by an imbalance between beneficial and harmful microbes in the gut. Dysbiosis is associated with a host of chronic diseases, including inflammatory bowel disease, metabolic disorders, neurological conditions, chronic kidney disease, and certain cancers.
Numerous studies have demonstrated that transferring beneficial fecal microbiota from a healthy individual to someone with a disease can alleviate symptoms, underscoring the importance of a core microbiome in maintaining overall health.
The research team employed artificial intelligence models to develop the “Two Competing Guilds” approach, which identifies the core microbiome’s essential structure composed of two distinct groups of bacteria: the Foundation Guild and the Pathobiont Guild. These groups engage in dynamic and stable interactions crucial for supporting human health and can predict personalized responses to immunotherapy in various diseases, irrespective of ethnicity, geography, or disease type.
Unlike conventional methods that rely on shared taxonomic units for microbiome analysis, the researchers utilized high-quality genomes assembled from metagenomic sequencing datasets. Each genome is labeled with a unique identifier, allowing for precise tracking of its ecological behavior. This genome-specific approach offers high resolution for analysis, includes genomes of novel bacteria not present in incomplete databases, and avoids mixing signal with noise.
According to Liping Zhao, the Eveleigh-Fenton Chair of Applied Microbiology at Rutgers, this research identifies resilient and interconnected bacteria in the gut that play a vital role in maintaining health, even in the face of challenges like dietary changes or illness. By focusing on these key microbes, the team has developed a new method for identifying the most crucial microbes for human health, leading to the discovery of the Foundation Guild and the Pathobiont Guild.
The Foundation Guild, essential for structuring and stabilizing the gut microbiome, breaks down dietary fibers and produces short-chain fatty acids crucial for gut health. On the other hand, the Pathobiont Guild, while necessary for immune education, can drive disease progression when it becomes dominant. Maintaining a balance between these two guilds is critical for gut health, with dysbiosis occurring when the balance shifts in favor of the Pathobiont Guild.
The model developed by the research team not only identifies these core bacterial guilds but also shows how they can be nurtured to maintain dominance. By targeting the fiber-degradation genes of the Foundation Guild, personalized dietary recommendations can be made to support the ecological dominance of these key microbes. This model sets a new standard for identifying members of the core microbiome, requiring stability even in the face of environmental changes.
Moving forward, Zhao and his team plan to conduct trials to refine personalized therapies aimed at restoring and maintaining the dominance of the Foundation Guild in patients with severe dysbiosis. By applying the Two Competing Guilds model in clinical settings, they aim to develop practical treatments that can significantly improve patient outcomes in conditions previously deemed irreversible.
This collaborative effort, involving experts from Rutgers, Shanghai Jiao Tong University, Tufts University Medical School, and other institutions, was supported by the New Jersey Institute for Food, Nutrition, and Health at Rutgers, CIFAR, Notitia Biotechnologies Company, and the Eveleigh-Fenton Endowed Chair Fund. This research marks a milestone in microbiome studies, offering insight into the crucial role of gut microbes in human health and paving the way for personalized therapies and precision nutrition tailored to individual needs.
