Challenges and opportunities of strain diversity in gut microbiome research

Abstract

Just because two things are related does not mean they are the same. In analyzing microbiome data, we are often limited to species-level analyses, and even with the ability to resolve strains, we lack comprehensive databases and understanding of the importance of strain-level variation outside of a limited number of model organisms. The bacterial genome is highly plastic with gene gain and loss occurring at rates comparable or higher than de novo mutations. As such, the conserved portion of the genome is often a fraction of the pangenome which gives rise to significant phenotypic variation, particularly in traits which are important in host microbe interactions. In this review, we discuss the mechanisms that give rise to strain variation and methods that can be used to study it. We identify that while strain diversity can act as a major barrier in interpreting and generalizing microbiome data, it can also be a powerful tool for mechanistic research. We then highlight recent examples demonstrating the importance of strain variation in colonization, virulence, and xenobiotic metabolism. Moving past taxonomy and the species concept will be crucial for future mechanistic research to understand microbiome structure and function.

Pangenome-based design of strain-specific primers allows the specific monitoring of engraftment in different habitats

“…Similarly, for L. plantarum, one genome with an ANI above 99.99% compared to L. plantarum WCFS1 is available. A signi cant challenge in developing strain-speci c primers is the debate on the criteria that differentiate two strains from one another [22][23][24][25] . We used a pragmatic strain de nition similar to Dijkshoorn et al (2000) 23 .…”

Akkermansia muciniphila modifies the association between metal exposure during pregnancy and depressive symptoms in late childhood

“…Additionally, a convenience sampled subset of participants (n = 123) contributed stool samples when the children reached ages 9–11 years. 26 Of the 123 participants with stool samples, 112 also had complete outcome data. The research protocols for both the main PROGRESS study and its microbiome sub-study underwent thorough review and were granted approval by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai in New York and the National Institute of Public Health in Cuernavaca, Mexico.…”

“…Details of the gut microbiome sampling and processing procedures have been previously published. 26 Briefly, participants were recruited during the 9–11-year PROGRESS study visit. Stool samples were collected by participants at home, processed using the Fast method at the clinic in Mexico City, and promptly stored −70°C.…”

“…Exposure to toxic metals is also associated with the composition, diversity, and functional activities of the GM. 22 – 25 We previously found that higher prenatal lead exposure reduced the diversity and abundance of beneficial taxa within the GM in children during mid-childhood (9-11 years) 26 , 27 Although metals have been linked to both alterations of the GM and increased depression symptoms, the specific role of A. muciniphila in modifying the association between metal exposure and depression has yet to be examined. This study, therefore, investigates the role of A. muciniphila in modifying the association between prenatal metal clique and depressive symptoms in late childhood.…”

Molecular ecology of microbiomes in the wild: Common pitfalls, methodological advances and future directions

“… Determine microbial strain diversity and evolution within hosts . Microbial communities are often highly heterogeneous and different strains of a single microbial species can exhibit significant genetic and functional variability (Anderson & Bisanz, 2023; Goyal et al., 2022). For example, a shift in Escherichia coli clones was documented in the gut microbiome of ageing mice, and these were characterized by an increase in bacterial mutations targeting stress‐response genes (Barreto et al., 2020).…”