Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity

Abstract

Background: Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment.

Results: Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA.

Conclusions: Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

Keywords: Epidemiology; Hispanic population; Microbiome; Mycobiome; Obesity.

Fig. 1

Relative frequency (median) and variability (interquartile range) of the 20 most abundant bacterial genera, among participants born in the mainland USA and those born in Latin America. Bar plots show the top 20 OTUs by order of abundance combined at the genus level using the phyloseq package. Boxes were colored based on the degree of statistical significance between US-born and foreign-born participants according to Wilcoxon signed-rank test to evaluate statistical significance between groups

Fig. 2

Correlates of gut bacterial (left) and fungal (right) microbiome in Hispanic/Latino residents of the USA, ranked by R² values. Correlations were calculated using ordination based on pairwise Bray-Curtis distances. PERMANOVA analysis using the adonis function from the vegan package was used to assess statistical significance. The figure shows the top 35 variables, all with P values < 0.05, ranked by the estimated effect size. Variables were examined individually, rather than in a multivariable model containing all variables. Except where indicated by an asterisk, all variables met q value criteria < 0.05

Fig. 3

Association of birthplace and acculturation-related variables with bacterial 16S (a) and fungal ITS1 (b) gut microbiome features. a Bacterial microbiome associations. Shown are the results of models adjusted for age (except for the model for age at relocation), sex, field center, intake of vegetables without potatoes, intake of whole fruit, intake of whole grains, moderate-to-vigorous physical activity (continuous), BMI (six groups), diabetes (three groups), length of visit to home country (continuous), education level (four groups), income level (five groups), antibiotic in last 6 months (binary), and metformin use (binary). Plot shows linear regression beta estimates and 95% confidence intervals for mean standardized gut microbiome outcomes. Estimates for which q value was less than 0.05 are shown in blue. Groups with less than 15 individuals were excluded from comparison, specifically: among individuals born in the US mainland, group sizes were as follows: South American, 7; Cuban, 12; Central American, 7; Dominican, 5. Sample sizes (n) for panel a are the same as those displayed in panel b. b Fungal microbiome associations, analyzed in similar manner as described in A. No estimates in panel b had a q value less than 0.05. Arrows indicate that the upper confidence limit exceeded the range of the X axis. PCoA1 and PCoA2 denote first and second principal coordinate from principal coordinate analysis.

Fig. 4

Linear regression analyses relating Prevotella to Bacteroides ratio with age at relocation to the mainland USA, among individuals who relocated to the USA before age 26. At the time they were studied, all cohort members were 25 years or older. Thus, by limiting to those who relocated to the mainland USA between birth and age 25, we could make a comparable analysis of age at relocation within groups defined by attained age. For example, only the oldest age groups of 55–64 years old (blue) or 65+ years old (magenta) could have contained an individual who had migrated at age 50 years old. However, any of the groups defined by attained age could have contained an individual who had migrated during childhood. As expected, after exclusion of those who relocated after age 26, there was no correlation between age at relocation and current age (Additional file 1: Figure S4). Within each of the groups defined by attained age, we observed a trend of increasing Prevotella to Bacteroides ratio with older age at relocation to the mainland USA

Fig. 5

Summary of findings relating to acculturation and GMB among US Latinos. The graphs summarize the results relating birthplace and migration history with summary measures of GMB including Prevotella to Bacteroides ratio, bacterial and fungal diversity. Older age at arrival to the mainland USA, consistent with the least exposure to the USA and the lowest acculturation to the US lifestyle, was associated with the highest Prevotella to Bacteroides ratio. This profile also went along with high fungal alpha diversity. Results for the bacterial GMB community were more complex. High bacterial diversity was found among the US born, and also among the group who relocated to the mainland USA from Latin America in older adulthood. The lowest bacterial alpha diversity was observed among those relocating from Latin America to the mainland USA during early life. Values were derived from fitted multivariate linear regression models as predicted mean outcomes in each category of birthplace and age at relocation, holding model covariates constant at either their mean value (for continuous variables, length of visit to home country/territory, intake of whole fruits, whole vegetables and whole grains, moderate-to-vigorous physical activity) or at the value of the most frequent category variable response (sex = female, field center = Chicago, body mass index = overweight, glycemic status = abnormal, metformin use = no, education = greater than high school level, annual income = $20,000 to $40,000/year, and antibiotic use in the last 6 months = no)

Fig. 6

Association of gut microbiome features with obesity defined by body mass index. Beta and 95% confidence intervals were derived from linear regression models relating body mass index categories with 16S Shannon index (left) and Prevotella to Bacteroides ratio (right), after adjustment for age, sex, field center, intake of vegetables without potatoes, intake of whole fruit, intake of whole grains, moderate-to-vigorous physical activity (continuous), diabetes (three groups), length of visit to home country (continuous), education level (four groups), income level (five groups), antibiotic in last 6 months (binary), and metformin use (binary). Asterisks indicate P < 0.05. Body mass index (BMI) defined as normal, 18.5 to 25 kg/m²; overweight, 25 to 30 kg/m²; class I obesity, 30 to 35 kg/m²; class II obesity, 35 to 40 kg/m²; and class III obesity, BMI above 40 kg/m². CI, confidence interval