Diversifying your diet portfolio: potential impacts of dietary diversity on the gut microbiome and human health

See corresponding article on page 1049.

It is well established that the trillions of microbes that reside within the human body are not just passengers, but active participants in sustaining human health. The gut microbiome—that is, the genomic contents of the microbes present in the human gut—includes many times more genes than are present in the human genome, with critical functions including biosynthesis of essential vitamins, nutrient harvest, and generation of metabolites from undigested food products that can impact human health at sites far from the gut. What we eat is a major determinant of which microbes take up residence in our guts, with diet estimated to account for 20% of the variation in the microbial structure in humans (1). Microbiome perturbations have been linked to many, if not all, diet-related chronic diseases (2). These findings give rise to the possibility of changing our diet to change our health status, by way of changing our microbiome. Proposed microbiome-directed strategies include recommendations that are backed by current dietary guidelines, such as consuming whole-plant foods and fish and avoiding processed foods, which have been linked to potentially adverse microbiome changes (2).

An article in this issue of the American Journal of Clinical Nutrition begins to build a foundation for considering dietary diversity as another modifiable factor with relevance to microbiome compositions and human health. Increased dietary diversity intuitively would be expected to result in increased microbiome diversity and potential robustness to perturbations (3), but this has been the subject of very few studies to date, in part due to a lack of consensus on how to measure dietary diversity (4). Xiao et al. analyzed data from 1916 participants in the Guangzhou Nutrition and Health Study (GNHS), a community-based, prospective cohort study of healthy, older adults (average age, 59.2 years) living in Guangzhou, a city in South China, and sought replication using data from 1320 participants in the China Health and Nutrition Survey (CHNS), a longitudinal, population-based survey with data available from adults (average age, 48.2 years) from 11 provinces and megacities across China (5). Participants in both cohorts completed FFQs asking about intakes of over 70 foods over the prior year, and each food was assigned to 1 of 6 food groups: grains, vegetables, fruits, dairy and dairy products, legumes and legume products, and meat and meat alternatives (including fish, eggs, and nuts). Food groups where participants reported eating at least 2 servings per week were assigned 1 point, and points were summed for each participant to generate a dietary diversity score ranging from 0 to 6. Participants in both the GNHS and CHNS provided stool samples for microbiome profiling via sequencing of the 16S ribosomal RNA region. The GNHS participants underwent more extensive profiling than the CHNS participants, including shotgun metagenomic sequencing of all DNA in stool samples and blood sample measurements of markers of metabolic disease risks.

In both cohorts, a substantial proportion of subjects routinely ate foods in all 6 food groups (dietary diversity score = 6; 53% of GNHS participants and 34% of CHNS participants), and these subjects were compared to those with dietary diversity scores <6. In accordance with smaller studies utilizing different methods of determining dietary diversity, including a nutrient tree–based method in a healthy US cohort (6), the healthy food diversity index in elderly subjects (7), the Dietary Variety Score in a Chinese population (8), and dietary Shannon diversity in children with autism spectrum disorder (9), Xiao et al. found positive associations between dietary diversity and multiple gut microbial diversity metrics. Additionally, gut microbiome compositions significantly differed between those with dietary diversity scores of 6 and those with scores <6. Two fecal microbial genera, Anaerotruncus and Veillonella, were enriched in association with high dietary diversity in both cohorts, and shotgun metagenomic sequencing in the GNHS cohort identified additional genera associated with dietary diversity. These taxa exhibited minimal overlap with those identified by a study of Dietary Variety Scores and gut microbial compositions in Chinese participants (8), perhaps due to methodological differences.

Metabolomic profiling of stool and serum samples in the GNHS cohort revealed associations of dietary diversity with fecal metabolites, including positive associations with long-chain unsaturated fatty acids, and with serum metabolites, including negative associations with 4 specific secondary bile acids: glycodeoxycholic acid (GDCA), taurodeoxycholic acid (TDCA), glycolithocholic acid 3-sulfate, and nordeoxycholic acid. Intriguingly, in cross-sectional analyses, 3 of these bile acids were associated with at least 1 cardiometabolic risk factor; for example, both GDCA and TDCA were positively associated with fasting insulin. While this constellation of findings raises the possibility that dietary diversity impacts the microbiome and circulating metabolome in a manner that reduces risks of cardiometabolic diseases, the authors demonstrate in mediation analyses that these relationships are complex and that a specific causal pathway cannot be inferred from these data, and data were not available for replication of this portion of the study. So, it remains to be seen whether dietary diversity truly impacts health outcomes via microbial mechanisms.

This article points to several other open questions. Dietary diversity is 1 of several metrics for dietary assessment, along with measurements of individual nutrients and adherence to broader dietary patterns. It is not clear whether dietary diversity itself impacts the microbiome and metabolome or whether observed associations with dietary diversity are attributable to a tendency of high dietary diversity to cooccur with other nutritional features. Indeed, Xiao et al. found that dietary diversity scores were positively correlated with the Chinese Healthy Eating Index (Spearman correlation, 0.46). Determining which specific features of the diet most effectively sustain a health-promoting microbiome is a challenging but worthy goal that is critical to informing evidence-based dietary recommendations.

Interestingly, Xiao et al. analyzed repeated FFQs in both cohorts and found that dietary diversity scores exhibited relatively low intraclass correlation coefficients: 0.43 (95% CI: 0.36, 0.50) in the GNHS over an average of 6.1 years between FFQs and 0.42 (95% CI: 0.36, 0.48) in the CHNS over an average of 4.1 years between questionnaires. Changes over an individual's lifetime in dietary diversity could be related to shifts in household income, employment status, physical activity, and mental and physical health. Indeed, dietary diversity has been linked to gradients of socioeconomic status and is a marker of food security (4). If future studies confirm that dietary diversity contributes to human health via effects on the microbiome, it may represent an important modifiable contributor to dysbiotic drift, whereby environmental forces drive microbial dysbiosis in a way that disproportionately impacts socioeconomically disadvantaged populations (10). However, before such a conclusion can be reached, future studies need to reach a consensus on how to define dietary diversity and supportive functional and experimental studies are required to determine whether and how dietary diversity could be modified to optimize the human microbiome.

Notes

The authors reported no funding received for this study.

Abbreviations used: CHNS, China Health and Nutrition Survey; GDCA, glycodeoxycholic acid; GNHS, Guangzhou Nutrition and Health Study; TDCA, taurodeoxycholic acid.