What constitutes a healthy human gut microbiome? ILSI NA investigates…

The paper is open access in the Journal of Nutrition , was described as “timely and very much needed” by Dr Jessica Ter Haar, PhD, scientific director at the International Probiotics Association, as it addresses the knowledge gaps regarding a healthy and dysbiotic gut microbiome. The expert panel was convened following a December 17, 2018 workshop that included over 40 invited academic, government, and industry experts in Washington, DC. One of the key objectives was to establish if the current evidence was sufficient could clarify measurable gut microbiome characteristics, which could serve as biomarkers of “health”. The authors, led by Dr Michael McBurney, reached seven conclusions, including: 1) There are not yet mechanistic links between how specific changes in the structure of the gut microbiome affect function or markers of human health; 2) We also still do not know if dysbiosis is a “cause, consequence, or both of changes in human gut epithelial function and disease” , they wrote; 3) People have highly individualized microbiome communities, and there is a lot of variation between people for how they respond to perturbation of their microbiome. Also, microbiome communities tend to be stable over long time periods (years); 4) A “comprehensive, multidisciplinary research agenda” is needed to elucidate the relationships between gut microbiome and host health; 5) Research is needed to determine and validate “biomarkers and/or surrogate indicators of host function and pathogenic processes based on the microbiome need” , wrote the authors. Normal ranges for such indicators and biomarkers also need to be determined; 6) Future studies should combine measurements of how the microbiome responds to an exposure or intervention with “validated microbiome-related biomarkers and/or surrogate indicators with multi-omics characterization of the microbiome” ; and 7) Future studies should also require repeated measures within individuals to account for important short- and long-term microbiome-related dynamic changes to the health of the host. Such changes may be missed using static genetic sampling. “Extremely helpful” Commenting independently on the findings of the research, Dr Jessica Ter Haar, PhD, scientific director at the International Probiotics Association, called the paper a “Timely and very much needed initiative by NA ILSI”. Dr Ter Haar added that the collective insights on attributes of a healthy microbiome that could be extremely helpful for probiotic research include: “ Microbial diversity [in adults] is negatively correlated with stool consistency and stool frequency, and stool consistency was shown to make the largest contribution to interindividual fecal microbiota variation, although its overall contribution to the total variation is still small.” and “ Longer colonic transit times [in adults] have been positively correlated with gut microbiota diversity and richness, a shift in microbial metabolism from carbohydrate fermentation to protein catabolism, and higher urinary levels of potentially deleterious protein-derived compounds .” The acknowledgement of the substantial knowledge gap regarding a healthy and dysbiotic gut microbiome and also if such things can actually be defined and so on is responsible, she said, and must be re-emphasized until the microbiome field can adequately form consensus. “Until then, the microbiome cannot be utilized or expected to be utilized as a biomarker of health or dysbiosis,” said Dr Ter Haar. “Another encouraging section of the manuscript was the discussion of the technical challenges to studying the microbiome, though proposing the way forward has been suggested by many in the field, we still have yet to see strong consensus and standards emerge on the whole. This cannot simply rest at ‘we need to do more’, but rather must migrate into the phase of actually doing more to harmonize the research approaches and standards,” she said. Dr Ter Haar did note that she was disappointed with the authors’ discussion around probiotic colonization and alteration of microbiome communities, as these two points are not established markers of probiotic efficacy. “However, to their credit, the authors did go on to mention the hypothesis that probiotics may functionally affect the gut microbiota,” she added. “The last part of the manuscript described useful high level thoughts on limitations, how to study the microbiome and what is missing, but again, we must wait and see if this excellent synthesis of the state of the field will catapult further developments in the right direction. It is clear that the microbiome is essential to health (especially the gut microbiome), but until we stop comparing apples to cold meat, we will be unable to capitalize on the huge potential of the field,” concluded Dr Ter Haar. Source: Journal of Nutrition Published online ahead of print, doi: 10.1093/jn/nxz154 “Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions” Authors: M.I. McBurney et al.