AI models help redefine core microbiome for personalized therapies

Researchers at Rutgers University-New Brunswick, along with international collaborators, have introduced a novel method for identifying the crucial set of gut microbes commonly found in humans and essential for health.

The researchers, whose study was published in Cell, said the discovery offers innovative opportunities for precision nutrition and personalized therapies aimed at managing chronic diseases associated with gut microbiome imbalances, including diabetes, inflammatory bowel disease and cancer.

The core microbiome refers to a set of microbes in the digestive tract that play a critical role in maintaining functions such as digestion, immune defense and mental health. When the core microbiome is reduced or lost, it can lead to a condition known as dysbiosis—an imbalance between beneficial and harmful microbes in the gut. Dysbiosis has been linked to numerous chronic diseases, including inflammatory bowel disease, metabolic disorders, neurological conditions, chronic kidney disease and certain cancers.

Many studies have shown that the transfer of beneficial fecal microbiota from a healthy colon to a diseased colon can alleviate these conditions, strongly indicating that a core microbiome is crucial for maintaining our health.

The core microbiome’s essential structure—two distinct groups of bacteria, termed the foundation guild and the pathobiont guild—engages in dynamic and stable interactions that are crucial for supporting human health. Utilizing artificial intelligence models, the “two competing guilds” approach classifies cases from controls across diverse populations, unaffected by ethnicity, geography or disease types, and predicts personalized responses to immunotherapy in four different diseases.

The field has yet to reach a consensus on what exactly constitutes the core microbiome or how to accurately identify these key microbial players.

Conventional methods of microbiome analysis often define the core microbiome using commonly shared taxonomic units, such as species or genus, within a human population. However, these taxa can have limited resolution. For example, within a single species, there may be both beneficial and harmful strains. The well-known gut bacterial species E. coli includes mostly benign strains, but E. coli O157 can cause serious foodborne illness.

This new study overcomes these limitations by using high-quality genomes directly assembled from metagenomic sequencing datasets. Each genome is labeled with a universal unique identifier for tracking its ecological behavior. This genome-specific approach not only provides high resolution for analysis, avoiding the mixing of signal with noise, but includes genomes of novel, unclassifiable bacteria not constrained by incomplete databases.

“Our research identifies the bacteria in the gut that stay connected, no matter what challenges the body faces, such as dietary changes or illness,” said Liping Zhao, the Eveleigh-Fenton Chair of Applied Microbiology and a professor in the Department of Biochemistry and Microbiology in the Rutgers School of Environmental and Biological Sciences. “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.”

This approach led to the identification of two distinct and opposing groups of core gut bacteria: the beneficial foundation guild and the necessary but potentially harmful pathobiont guild.

The foundation guild is crucial for structuring and stabilizing the whole gut microbiome. These bacteria break down dietary fibers and produce short-chain fatty acids (SCFAs) such as butyrate, which are crucial for gut health by supporting the gut barrier, reducing inflammation and serving as an energy source for colon cells. SCFAs are also critical for suppressing harmful bacteria.

In contrast, the pathobiont guild, while necessary in small amounts for immune training and vigilance, can drive disease progression when it becomes ecologically dominant.

The seesaw-like balance between these two guilds is critical. When the foundation guild dominates, gut health is maintained. However, when the balance tips in favor of the pathobiont guild, dysbiosis occurs, potentially leading to inflammation that can aggravate various chronic conditions.

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

Targeting the fiber-degradation genes of the foundation guild, personalized dietary recommendations can be made to support the ecological dominance of these key microbes.

The two competing guilds model provides both a new method and a new standard for identifying members of the core microbiome. By requiring that the members of the core microbiome aren’t only commonly shared within a population, but stably connected despite dramatic changes in their environments, the model sets a new benchmark for microbiome research, according to Zhao.

Zhao and his team plan to conduct a series of trials to further refine personalized therapies aimed at restoring and maintaining the ecological dominance of the foundation guild in patients with severe dysbiosis. By applying the two competing guilds model in clinical settings, they aim to translate their research into practical treatments that can significantly improve patient outcomes in conditions previously considered irreversible.