Intestinal Microbiome Balance Test: Background

The human gastrointestinal tract is teeming with microbes… indeed, with up to 100 billion of them they outnumber the number of cells in our bodies.  These microbes are comprised largely of bacteria which distribute across a wide array of classifications including kingdom, phylum, class, genus, species, and strain. Over the past few years our ability to differentiate between these classifications has improved, first using pyrosequencing analysis differentiation and now utilizing more sophisticated shotgun metagenomics approaches.  Applying these approaches, much has been learned about how an individual’s microbial composition is unique both quantitatively and qualitatively. What is now understood is that extreme inter-individual variation exists in the relative amounts of microbial taxon. However, a core of pattern of microbiota persists through the majority of the population, which is accompanied by smaller inter-individual variation for specific microbiota, and is largely unique to a given individual. The inter-individual differences in the microbiome make-up across 29 participants each tested multiple times in a recent clinical trial are shown in Figure 1.

Figure 1: Inter-individual Variation in the Gut Microbiome

Note. Bars reflect repeated profiling in each of 29 individuals

It is now understood that manifold factors impact the composition of the gut microbiome. Such factors including diet, stress, infant feeding method, pharmaceuticals, geography, and life cycle stage can profoundly alter the make-up of the gut microbial population (Figure 2).

Figure 2:  Microbiome: Onset and Shaping Through Life Stages

As importantly, recent research has delineated how these various factors shape the gut microbiome in ways that can both contribute to either disease states or improve health and wellness. A depiction of mechanisms through which the composition of the microbiome contributes negatively or positively to health is found in Figure 3. Secondary metabolites produced by certain bacteria in the GI tract which possess the capacity to alter health either negatively or positively include short chain fatty acids (SCFA), trimethylamine oxide (TMAO), lipopolysaccharides (LPS), antioxidants, and indoxyl sulphate.

Figure 3: The Gut Microbiome in Health and Disease

Intestinal Microbiome Balance Test: Rationale

It is now increasingly recognized that the microbiome architecture can inform as to optimal dietary and natural health product use strategies. As indicated in Figure 4, scientific evidence based on robustly designed and implemented clinical trials can predict what is the best food or natural product supplement to use to optimize health outcomes, based on an individual’s specific microbiome pattern. This is done through use of randomized clinical trials which represent the gold standard to achieve evidence-based medicine. These trials allow for identification of the numerous factors that coexist and interact to influence the effect diet and natural products can have on health outcomes. Data-processing algorithms can now be used to identify aspects of the clinical profile of individuals including data on the microbiome that predict such health responses.

Figure 4: Dietary Intervention to Modulate the Gut Microbiome- How Far Away Are We From Precision Medicine

Francesca De Filippis, PhD, Paola Vitaglione, PhD, Rosario Cuomo, MD, Roberto Berni Canani, PhD, and Danilo Ercolini, PhD

Using such approaches, evidence has been accumulating showing that individuals with certain gut profiles will show distinct responses to dietary interventions. The metabolic response to a diet intervention is thus person-specific where the same food or natural product will produce different responses across individuals. For instance, when health marker responsiveness to a high fibre-low calorie diet was assessed across a group of individuals using a carefully controlled clinical trial, the level of responsiveness was found to be related to the level of microbiome diversity as well as the ratio of Prevotella to Bacteriodes. These data suggest that encouraging diet or supplement strategies favoring a high Prevotella/Bacteroides ratio, in individuals identified through microbiome testing as having low ratios, would improve overall health outcomes (Figure 5).

Figure 5: Dietary Interventions to Modulate the Gut Microbiome

Similarly, researchers have shown that using data from gut microbiome analysis, blood testing, questionnaires, and anthropometrics, together with AI based computational analysis, a personalized nutrition strategy could be predicted which would lower postprandial glucose level responses across a group of 800 individuals (Figure 6). These data again point to the usefulness of measuring microbiome distribution as a means of predicting optimal dietary and natural health product interventions. These results collectively point to the concept of a mechanism-free, empirical predictive strategy for determining a natural health product strategy that is appropriate for a given individual, based on parameters including the microbiome composition. This research highlights the usefulness of a next generation of probiotics as a means of converting non-responders to responders to natural products.

Figure 6: Study Results Support Microbiome-based Recommendations

Dietary intervention based on the algorithm resulted in significantly lower postprandial responses and consistent alterations to gut microbiota configuration.

Intestinal Microbiome Balance Test: Description

Accordingly, NFH is working in partnership with CosmosID to provide a comprehensive determination of the gut microbiome profile using whole shotgun metagenome sequencing. This sequencing approach is far more powerful than the commonly used bacterial 16s rRNA sequence method. By using the latest Illumina next generation sequencing platforms, we enable detection of whole DNA sequences, host DNA, multiple bacterial genes, and functions, as well as, metabolites and functional pathways. With over 3,000,000 NGS reads, the shotgun metagenome sequencing approach provides the most comprehensive assessment of gut microbiota available today.

Approaches to interpreting the results of shotgun sequencing results have also been advancing. For instance, recently Gupta et al aggregated abundance values for individual species to generate the Gut Microbiome Health Index (GMHI), a biologically-interpretable mathematical formula for predicting the likelihood of disease independent of the clinical diagnosis. The GMHI is formulated based on 50 microbial species associated with a healthy gut ecosystem. The 50 species were identified through a multi-study, integrative analysis on 4347 human stool metagenomes from 34 published studies across healthy and 12 different non-healthy conditions (Gupta et al). Your NFH gut microbiome adopts a similar approach to the GMHI, providing listings of both beneficial and deleterious microbial species associated with the gut ecosystem.

Gupta, V.K., et al. A predictive index for health status using species-level gut microbiome profiling. Nat Commun 11, 4635 (2020).

The NFH Testing/CosmosID results report interprets the complete microbial profile in terms of functional capacity and relation to health using a variety of useful indices that reflect risk for health disorders. This interpretation feature of the report makes it easy to discuss a patient’s personalized findings with them and facilitates arriving at the correct probiotic and prebiotic supplementation strategy to optimize health.