Our group was the first to identify specific members of the human gut microbiome whose relative abundance in the gut microbiome is explained in part by the genotype of the host (so-called ‘heritable’ microbiota). Using gut microbiome data that we generated for >3000 fecal samples obtained from genotyped twins in the UK, we generated a list of gut microbes under host genetic influence (Goodrich, 2014). This list is not unique to UK twins: it has since been validated in similar studies of populations from various parts of the world (Goodrich, 2017). We now use this list to guide our studies: what is special about the heritable microbes? What is it about human genetic variation that they respond to? Are they more likely than non-heritable microbes to be passed between close relatives? Does their strain diversity map on patterns of human migration?
We have identified aspects of human genetic variation that are associated with specific aspects of the microbiome (Goodrich, 2016). We have investigated further two that have functional consequences: (1) variation in the lactase LCT gene, which dictates lactose tolerance, and (2) salivary amylase AMY1 gene copy number, which dictates how readily starch is degraded in the mouth. How these are linked to the microbiome is described in Schmidt et al. (2020) and Poole et al. (2019). A conceptual view of how the microbiome interacts with the process of host genetic adaptation to new environments is provided in Suzuki and Ley (2020).
We take a broad view of the evolution of the human gut microbiome by placing it in the context of the vertebrate microbiome (Goodrich 2016). In a series of studies that survey the microbiome of wild animals, we have identified mammalian clades where bacteria and archaea show signs of having tracked with the diversification of their hosts (Youngblut 2019, 2020).
Within the human gut microbiome, bacteria of the little-studied family Christensenellaceae are highly heritable. We showed that they are also, along with a suite of other microbiota, enriched in lean versus obese individuals, and could show causality in germfree mice (Goodrich, 2014). We are currently delving into the multi-part symbiosis of these bacteria and archaea (Ruaud 2020). Our aim is to elucidate how they interact with each other and with the host to impact phenotype.