Bryan Merrill

selected publications

1. Cell

   Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes

   Carter, Matthew M., Olm, Matthew R.,  Merrill, Bryan D., Dahan, Dylan, Tripathi, Surya, Spencer, Sean P., Yu, Feiqiao B., Jain, Sunit, Neff, Norma, Jha, Aashish R., Sonnenburg, Erica D., and Sonnenburg, Justin L.

   Cell 2023

   Abs bioRxiv PubMed DOI PDF

   The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers of Tanzania and comparative populations in Nepal and California. We recovered 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource, expands our understanding of microbes capable of colonizing the human gut, and clarifies the extensive perturbation induced by the industrialized lifestyle.

2. Nature

   A metabolomics pipeline for the mechanistic interrogation of the gut microbiome

   Han, Shuo, Van Treuren, Will, Fischer, Curt R.,  Merrill, Bryan D., DeFelice, Brian C., Sanchez, Juan M., Higginbottom, Steven K., Guthrie, Leah, Fall, Lalla A., Dodd, Dylan, Fischbach, Michael A., and Sonnenburg, Justin L.

   Nature, Jul 2021

   Abs bioRxiv PubMed DOI PDF

   Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules, yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites in diverse sample types. We report the metabolic profiles of 178 gut microorganism strains using our library of 833 metabolites. Using this metabolomics resource, we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover a previously undescribed type of metabolism in Bacteroides, and reveal candidate biochemical pathways using comparative genomics. Microbiota-dependent metabolites can be detected in diverse biological fluids from gnotobiotic and conventionally colonized mice and traced back to the corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microorganisms and interactions between microorganisms and their host.

3. Cell Host Microbe

   Bacteroides thetaiotaomicron-Infecting Bacteriophage Isolates Inform Sequence-Based Host Range Predictions

   Hryckowian, Andrew J.,  Merrill, Bryan D., Porter, Nathan T., Van Treuren, William, Nelson, Eric J., Garlena, Rebecca A., Russell, Daniel A., Martens, Eric C., and Sonnenburg, Justin L.

   Cell Host Microbe, Sep 2020

   Abs bioRxiv PubMed DOI PDF

   Our emerging view of the gut microbiome largely focuses on bacteria, while less is known about other microbial components, such as bacteriophages (phages). Though phages are abundant in the gut, very few phages have been isolated from this ecosystem. Here, we report the genomes of 27 phages from the United States and Bangladesh that infect the prevalent human gut bacterium Bacteroides thetaiotaomicron. These phages are mostly distinct from previously sequenced phages with the exception of two, which are crAss-like phages. We compare these isolates to existing human gut metagenomes, revealing similarities to previously inferred phages and additional unexplored phage diversity. Finally, we use host tropisms of these phages to identify alleles of phage structural genes associated with infectivity. This work provides a detailed view of the gut’s "viral dark matter" and a framework for future efforts to further integrate isolation- and sequencing-focused efforts to understand gut-resident phages.

4. Science

   Robust variation in infant gut microbiome assembly across a spectrum of lifestyles

   Olm, Matthew R., Dahan, Dylan, Carter, Matthew M.,  Merrill, Bryan D., Yu, Feiqiao Brian, Jain, Sunit, Meng, Xiandong, Tripathi, Surya, Wastyk, Hannah C., Neff, Norma F., Holmes, Susan, Sonnenburg, Erica D., Jha, Aashish R., and Sonnenburg, Justin L.

   Science, Jun 2022

   Abs bioRxiv PubMed DOI PDF

   Infant microbiome assembly has been intensely studied in infants from industrialized nations, but little is known about this process in nonindustrialized populations. We deeply sequenced infant stool samples from the Hadza hunter-gatherers of Tanzania and analyzed them in a global meta-analysis. Infant microbiomes develop along lifestyle-associated trajectories, with more than 20% of genomes detected in the Hadza infant gut representing novel species. Industrialized infants-even those who are breastfed-have microbiomes characterized by a paucity of Bifidobacterium infantis and gene cassettes involved in human milk utilization. Strains within lifestyle-associated taxonomic groups are shared between mother-infant dyads, consistent with early life inheritance of lifestyle-shaped microbiomes. The population-specific differences in infant microbiome composition and function underscore the importance of studying microbiomes from people outside of wealthy, industrialized nations.

5. Cell

   Gut-microbiota-targeted diets modulate human immune status

   Wastyk, Hannah C., Fragiadakis, Gabriela K., Perelman, Dalia, Dahan, Dylan,  Merrill, Bryan D., Yu, Feiqiao B., Topf, Madeline, Gonzalez, Carlos G., Van Treuren, William, Han, Shuo, Robinson, Jennifer L., Elias, Joshua E., Sonnenburg, Erica D., Gardner, Christopher D., and Sonnenburg, Justin L.

   Cell, Aug 2021

   Abs bioRxiv PubMed DOI PDF

   Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.