Despite considerable variation in gut microbiome composition across geography, a healthy gut microbiome is defined by a high microbial diversity and richness of microbial genes, ecologic stability (defined as resistance against community structure change under stress and resilience to return to baseline following perturbation rapidly), and functional competence (including desirable metabolic and trophic provisions to the host)1.

While early life is a critical period in gut microbiome development due to its influence on the host immune system and metabolism, little is known about how gut microbiome changes are associated with health outcomes in the first years of life.

A new observational study shows that gut microbiome development in the first two years of life is predictable, relies on infant exposures, and is associated with current or later health problems2.

The authors explored how stool microbiome changes mirror health outcomes and well-being in a cohort of 984 term-born Finnish infants from birth to 5 years. The infants’ previous gut microbiome composition, birth mode, defecation rate, and diet and family composition were the factors that most affected microbiome development.

The infants’ gut microbiome development followed one of five distinct trajectories that were more informative in predicting later health outcomes compared to specific community members, with differences more apparent for the first 6 months. The most common trajectory consisted of an initial high abundance of Bifidobacterium and Bacteroides that later declined and were replaced by Veillonella and then by Faecalibacterium and Lachnospiraceae members, which showed the most stable composition compared to the other four trajectories. This trajectory was associated with a reduced risk of allergy symptoms and upper respiratory infections in the first 2 years, allergic rhinitis at 5 years, and overweight at 5 years.

In contrast, some particular dysbiotic trajectories were linked to different health outcomes. Infants showing a rapid decline in Bifidobacterium and a transient increase in Clostridium and Klebsiella had a higher risk of atopy at 2 years, and allergy symptoms during the first 2 years. Similarly, infants with a high abundance of Clostridium and Klebsiella throughout the first 6 months had a high risk of being diagnosed with atopy at 5 years. The authors noted that some of the trajectories identified can be reiterated in other cohorts collected in the first two years of life from infants from other countries.

In line with these findings, Mayo researchers recently developed a tool based on stool microbiomes, called Gut Microbiome Wellness Index 2, that shows 80% accuracy in differentiating healthy individuals from those with 11 disease conditions. The findings are based on 8069 stool shotgun metagenomes spanning six continents (26 countries) and including diverse ethnicities and cultures. The higher (or more positive) the index, the higher the confidence in classifying stool metagenomes as healthy, while a negative value classifies it as non-healthy3.

This tool is an improvement of a previous tool developed by the same researchers. It is suggested that the tool can detect even subtle changes in gut health, thus identifying if a person might recover from a disease or has a high risk of disease. The authors also found that this index could be a valuable tool for studying the impact of diet on the gut microbiome and how it recovers following antibiotics3.

Another new study by Liping Zhao and colleagues at the Rutger Center for Microbiome Analysis, along with international collaborators, has utilized artificial intelligence models for identifying a set of gut microorganisms that play a critical role in digestion, immune responses, and mental health. What is new with the analysis is that it is based on genome-specific analysis and database independence, and it is focused on stable gut microbiome interactions4.

The core microbiome’s structure includes two distinct groups of bacteria (i.e., the Foundation Guild and the Pathobiont Guild) that compete with each other as an indicator of health and help differentiate cases from controls across 15 diseases across three continents and predict immunotherapy outcomes. Stable interactions within gut microbiome members appear more relevant than the abundance of microorganisms. These findings open a new potential way to disease prediction and classification and manage microbiome-related diseases through specific interventions that target the core microbiome related to health4.

 

References:

  1. Bäckhed F, Fraser CM, Ringel Y, et al. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe. 2012; 12(5):611-622. doi: 10.1016/j.chom.2012.10.012.
  2. Hickman B, Salonen A, Ponsero AJ, et al. Gut microbiota wellbeing index predicts overall health in a cohort of 1000 infants. Nat Commun. 2024; 15(1):8323. doi: 10.1038/s41467-024-52561-6.
  3. Chang D, Gupta VK, Hur B, et al. Gut microbiome wellness index 2 enhances health status prediction from gut microbiome taxonomic profiles. Nat Commun. 2024; 15(1):7447. doi: 10.1038/s41467-024-51651-9.
  4. Wu G, Xu T, Zhao N, et al. A core microbiome signature as an indicator of health. Cell. 2024. doi: 10.1016/j.cell.2024.09.019.