UC Irvine

The lifespan of people living in westernized countries is increasing, suggesting we are getting healthier; however, we are now struggling with a new health problem: the increasing incidence of chronic disease. We have only recently begun to appreciate the association of microbial colonization with health, and how changes in our lifestyles (i.e. diet, urbanization, sanitation) are affecting this association. Changes in microbial community composition have been linked with numerous acute and chronic disease states. Despite the microbiome’s strong correlation with health, there is still much work to be done in understanding the ideal structure and function of these human associated microbial communities.Humans first experience with microorganisms occurs during birth, when we are exposed to the maternal microbiome. Cervicovaginal microbes and their metabolic by-products critically influence the structuring and functioning of the early infant microbiome and immune system; however, global assessments of maternal microbes and metabolites are lacking. In Chapter 1, my co-authors and I address this knowledge gap by sequencing cervicovaginal fluid from 18 healthy mothers longitudinally throughout their pregnancy. Parallel to microbiome sequencing, we examined the vaginal metabolomes using GF-TOF and LC-MS/MS to broadly capture metabolites within this system. Additionally, we analyzed the metabolomes of offspring through their first year of life. We report strong metabolic biomarkers of microbiome composition within the cervicovaginal tract, which may ultimately be useful in future diagnostic and therapeutic endeavors for vaginal diseases like bacterial vaginosis (BV). We show a strong correlation between mannitol and the presence of Lactobacillus crispatus and speculate as to why a homofermentative vaginal lactobacillus may be generating mannitol via fructose reduction for redox purposes. In chapter 1, I focus on describing the early microbes and metabolites infants are exposed to during pregnancy and birth. Throughout our lives, our microbiomes are under constant selection by intrinsic (e.g., phage predation) and extrinsic (e.g., antibiotic use) factors. One strong architect of gut microbial composition is diet. Dietary fiber is a favored substrate of microbes deep within the colon, which is able to resist digestion by endogenous enzymes in order to feed the dense bacterial communities throughout the gut. In chapter 2, we conducted a two-week diet intervention study, asking whether an increase in dietary fiber intake through whole foods was capable of changing the gut microbial communities and associated metabolome. We show on a short time scale, increasing dietary fiber in the gut alters the microbial composition significantly, but does not change the abundance of metabolic by-products of fiber fermentation (short-chain fatty acids). While more work needs to be done to disentangle the relationship between how diet influences bacterial metabolites, our work illustrates how malleable gut microbial communities are to a change in diet. Finally, in chapter 3, I contributed context to a growing body of microbiome research that is woefully lacking microbiome characterizations from non-industrialized populations. We teamed up with anthropologists to study the microbiome of a remote community of people deep within the Ecuadorian Amazon. Our findings show that the microbiomes from these Conambo people are distinct from the microbiomes of industrialized individuals, containing a high abundance of VANISH taxa (volatile and/or associated negatively with industrialized societies of humans). Notably, nearly 40% of the average fecal metagenome consisted of reads mapping to Prevotellaceae. The Conambo people have unique diets, with a significant portion of their caloric intake coming from a cultural variant of cassava beer (“chicha”). Chicha is made by mastication and re-mastication of yuca root by women within each household. We show that while the initial inoculums of chicha are household specific, over the course of fermentation the communities converge on a more similar microbiome irrespective of household origin. These data contribute vitally towards the open question: how has industrialization shaped the microbiome?