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1.
bioRxiv ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39005279

ABSTRACT

BACKGROUND: Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remains less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called 'vanishing microbiomes' potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes across populations. RESULTS: Here, we investigate salivary microbiomes of 63 Nepali individuals representing a spectrum of lifestyles: foraging, subsistence farming (individuals that transitioned from foraging to farming within the last 50 years), agriculturalists (individuals that have transitioned to farming for at least 300 years), and industrialists (expatriates that immigrated to the United States within the last 20 years). We characterize the role of lifestyle in microbial diversity, identify microbes that differ between lifestyles, and pinpoint specific lifestyle factors that may be contributing to differences in the microbiomes across populations. Contrary to prevailing views, when geography is controlled for, oral microbiome alpha diversity does not differ significantly across lifestyles. Microbiome composition, however, follows the gradient of lifestyles from foraging through agrarianism to industrialism, supporting the notion that lifestyle indeed plays a role in the oral microbiome. Relative abundances of several individual taxa, including Streptobacillus and an unclassified Porphyromonadaceae genus, also mirror lifestyle. Finally, we identify specific lifestyle factors associated with microbiome composition across the gradient of lifestyles, including smoking and grain source. CONCLUSION: Our findings demonstrate that by controlling for geography, we can isolate an important role for lifestyle in determining oral microbiome composition. In doing so, we highlight the potential contributions of several lifestyle factors, underlining the importance of carefully examining the oral microbiome across lifestyles to improve our understanding of global microbiomes.

2.
Annu Rev Anim Biosci ; 10: 203-226, 2022 02 15.
Article in English | MEDLINE | ID: mdl-35167316

ABSTRACT

Animals harbor diverse communities of microbes within their gastrointestinal tracts. Phylogenetic relationship, diet, gut morphology, host physiology, and ecology all influence microbiome composition within and between animal clades. Emerging evidence points to host genetics as also playing a role in determining gut microbial composition within species. Here, we discuss recent advances in the study of microbiome heritability across a variety of animal species. Candidate gene and discovery-based studies in humans, mice, Drosophila, Caenorhabditis elegans, cattle, swine, poultry, and baboons reveal trends in the types of microbes that are heritable and the host genes and pathways involved in shaping the microbiome. Heritable gut microbes within a host species tend to be phylogenetically restricted. Host genetic variation in immune- and growth-related genes drives the abundances of these heritable bacteria within the gut. With only a small slice of the metazoan branch of the tree of life explored to date, this is an area rife with opportunities to shed light into the mechanisms governing host-microbe relationships.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Animals , Bacteria , Caenorhabditis elegans/genetics , Caenorhabditis elegans/microbiology , Cattle , Gastrointestinal Microbiome/genetics , Mice , Phylogeny , Swine
3.
Elife ; 102021 03 23.
Article in English | MEDLINE | ID: mdl-33755018

ABSTRACT

Changes in diet associated with domestication may have shaped the composition of microbes found in the guts of animals.


Subject(s)
Gastrointestinal Microbiome , Animals , Diet , Domestication , Humans , Industrial Development
4.
Biosci Rep ; 40(12)2020 12 23.
Article in English | MEDLINE | ID: mdl-33325526

ABSTRACT

Aldehyde dehydrogenases (ALDHs) catalyze the conversion of various aliphatic and aromatic aldehydes into corresponding carboxylic acids. Traditionally considered as housekeeping enzymes, new biochemical roles are being identified for members of ALDH family. Recent work showed that AldA from the plant pathogen Pseudomonas syringae strain PtoDC3000 (PtoDC3000) functions as an indole-3-acetaldehyde dehydrogenase for the synthesis of indole-3-acetic acid (IAA). IAA produced by AldA allows the pathogen to suppress salicylic acid-mediated defenses in the model plant Arabidopsis thaliana. Here we present a biochemical and structural analysis of the AldA indole-3-acetaldehyde dehydrogenase from PtoDC3000. Site-directed mutants targeting the catalytic residues Cys302 and Glu267 resulted in a loss of enzymatic activity. The X-ray crystal structure of the catalytically inactive AldA C302A mutant in complex with IAA and NAD+ showed the cofactor adopting a conformation that differs from the previously reported structure of AldA. These structures suggest that NAD+ undergoes a conformational change during the AldA reaction mechanism similar to that reported for human ALDH. Site-directed mutagenesis of the IAA binding site indicates that changes in the active site surface reduces AldA activity; however, substitution of Phe169 with a tryptophan altered the substrate selectivity of the mutant to prefer octanal. The present study highlights the inherent biochemical versatility of members of the ALDH enzyme superfamily in P. syringae.


Subject(s)
Aldehyde Oxidoreductases/metabolism , Bacterial Proteins/metabolism , Indoles/metabolism , Pseudomonas syringae/enzymology , Aldehyde Oxidoreductases/chemistry , Aldehyde Oxidoreductases/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Kinetics , Models, Molecular , Mutagenesis, Site-Directed , Mutation , Protein Conformation , Pseudomonas syringae/genetics , Structure-Activity Relationship , Substrate Specificity
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