Tobacco Smoking and the Fecal Microbiome in a Large, Multi-ethnic Cohort.

BACKGROUND: Increasing evidence suggests that tobacco smoking, a well-known driver of carcinogenesis, influences the gut microbiome; however, these relationships remain understudied in diverse populations. Thus, we performed an analysis of smoking and the gut microbiome in a subset of 803 adults from the multi-ethnic NYU FAMiLI study. METHODS: We assessed fecal microbiota using 16S rRNA gene sequencing, and clustered samples into Amplicon Sequence Variants using QIIME2. We evaluated inferred microbial pathway abundance using PICRUSt. We compared population ß-diversity, and relative taxonomic and functional pathway abundance, between never smokers, former smokers, and current smokers. RESULTS: We found that the overall composition of the fecal microbiome in former and current smokers differs significantly from that of never smokers. The taxa Prevotella and Veillonellaceae were enriched in current and former smokers, whereas the taxa Lachnospira and Tenericutes were depleted, relative to never smokers. These shifts were consistent across racial and ethnic subgroups. Relative to never smokers, the abundance of taxa enriched in current smokers were positively correlated with the imputed abundance of pathways involving smoking-associated toxin breakdown and response to reactive oxygen species (ROS). CONCLUSIONS: Our findings suggest common mechanisms of smoking associated microbial change across racial subgroups, regardless of initial microbiome composition. The correlation of these differentials with ROS exposure pathways may suggest a role for these taxa in the known association between smoking, ROS and carcinogenesis. IMPACT: Smoking shifts in the microbiome may be independent of initial composition, stimulating further studies on the microbiome in carcinogenesis and cancer prevention.

US nativity and dietary acculturation impact the gut microbiome in a diverse US population.

Little is known regarding the impact of immigrant acculturation on the gut microbiome. We characterized differences in the gut microbiome between racially/ethnically diverse US immigrant and US-born groups, and determined the impact of dietary acculturation on the microbiome. Stool samples were collected from 863 US residents, including US-born (315 White, 93 Black, 40 Hispanic) and foreign-born (105 Hispanic, 264 Korean) groups. We determined dietary acculturation from dissimilarities based on food frequency questionnaires, and used 16S rRNA gene sequencing to characterize the microbiome. Gut microbiome composition differed across study groups, with the largest difference between foreign-born Koreans and US-born Whites, and significant differences also observed between foreign-born and US-born Hispanics. Differences in sub-operational taxonomic unit (s-OTU) abundance between foreign-born and US-born groups tended to be distinct from differences between US-born groups. Bacteroides plebeius, a seaweed-degrading bacterium, was strongly enriched in foreign-born Koreans, while Prevotella copri and Bifidobacterium adolescentis were strongly enriched in foreign-born Koreans and Hispanics, compared with US-born Whites. Dietary acculturation in foreign-born participants was associated with specific s-OTUs, resembling abundance in US-born Whites; e.g., a Bacteroides plebeius s-OTU was depleted in highly diet-acculturated Koreans. In summary, we observed that US nativity is a determinant of the gut microbiome in a US resident population. Dietary acculturation may result in loss of native species in immigrants, though further research is necessary to explore whether acculturation-related microbiome alterations have consequences for immigrant health.

A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making.

Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood. We demonstrate that CaSR promotes sensorimotor decision making acutely through Gαi/o and Gαq/11 signaling, modulated by clathrin-mediated endocytosis. Combined, our results identify the first set of genes critical for behavioral choice modulation in a vertebrate and reveal an unexpected critical role for CaSR in sensorimotor decision making.