UC Irvine

Humans harbor a diverse microbiome in their gut including a diversity of bifidobacteria species. The bacterial group bifidobacteria (genus Bifidobacterium) is fundamental to the health of humans and animals. They are inhabitants of the gastrointestinal tract, vagina, and mouth of mammals and some insects. Bifidobacteria have gained notable attention as their presence in the gut has been correlated with many health-promoting benefits. While human bifidobacteria have been well studied, most focus on one strain at a time, without considering the variety that coexist in the gut. My thesis focused on the ecological and evolutionary forces driving the assembly, coexistence, and functioning of bifidobacterial diversity. Using a multidisciplinary approach that encompasses ecological and evolutionary theory, genomics, and microbial metabolism, my objectives were to: 1) uncover the trait and evolutionary associations bifidobacteria have with their animal hosts (Chapter 1); 2) assess bacterial responses to dietary fiber consumption in the human gut (Chapter 2); and 3) identify the functional consequences of bifidobacteria diversity (Chapter 3).

To address objective 1, I used a comparative genomics approach to investigate the adaptation of bifidobacteria to their hosts. I analyzed all the bifidobacteria genomes available in The National Center for Biotechnology Information (NCBI) repository. I identified the hosts from which the bifidobacteria strains were isolated, performed a multilocus phylogenetic analysis, compared the genetic relatedness of the strains to different hosts, and tested the degree to which variation in traits can be attributed to their hosts. I found that different species of bifidobacteria colonized different animal hosts and that traits related to fiber degradation were associated with particular hosts.

To tackle objective 2, I conducted a meta-analysis that included dietary fiber interventions that have examined the human gut microbiome (n=21). By synthesizing, reanalyzing, and conducting an in-depth phylogenetic analysis, I found consistent bacterial responses to short-term increases in dietary fiber consumption in healthy humans. Specifically, I found that fiber interventions decreased bacterial diversity and explained an average of 1.5% of compositional variation. Moreover, I identified specific bacterial taxa that responded to dietary fiber in humans. One taxon that drastically increased in response to fiber consumption across interventions was bifidobacteria.

To address objective 3, I tested how the diversity and richness of bifidobacteria isolates influence their coexistence and functioning (i.e., fiber degradation) using laboratory experiments. To do this, I obtained bifidobacteria isolates from the Human Microbiome Project (HMP), and I selectively isolated new strains from fecal samples collected at the University of California, Irvine. I conducted microcosm experiments that vary the diversity of bifidobacteria and characterized the functioning of the bacterial communities using flow cytometry (to count bacterial cells), lactate assays (to measure metabolite concentration), and next-generation sequencing (to decipher the bacterial community’s composition). I found that the diversity of isolates persisted, such that up to 7 strains coexisted. Moreover, metabolite production (e.g., lactate) increased with increasing bifidobacteria diversity. However, this was not the case for biomass production.Focusing on the ecology and evolution of an important taxon like bifidobacteria within the diverse gut community will provide a deeper understanding on the community assembly mechanisms that bacteria use to colonize specific hosts.