Biology subjects

Beiting, D. P.

Publications and source records attributed to Beiting, D. P..

23 records · Page 2Linked to original sources

bioRxiv2020

Remodeling of the maternal gut microbiome during pregnancy is shaped by parity

BackgroundThe maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies - referred to as maternal parity - as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans. ResultsUsing synchronized pregnancies and dense longitudinal monitoring of the microbiome in pigs, we describe a microbiome trajectory during pregnancy and determine the extent to which parity modulates this trajectory. We show that the microbiome changes reproducibly during gestation and that this remodeling occurs more rapidly as parity increases. At the time of parturition, parity was linked to the relative abundance of several bacterial species, including Treponema bryantii, Lactobacillus amylovorus, and Lactobacillus reuteri. Strain tracking carried out in 18 maternal-offspring quadrads - each consisting of one mother sow and three piglets - linked maternal parity to altered levels of Akkermansia muciniphila, Prevotella stercorea, and Campylobacter coli in the infant gut 10 days after birth. ConclusionsCollectively, these results identify parity as an important environmental factor that modulates the gut microbiome during pregnancy and highlight the utility of a swine model for investigating the microbiome in maternal-infant health. In addition, our data show that the impact of parity extends beyond the mother and is associated with alterations in the community of bacteria that colonize the offspring gut early in life. The bacterial species we identified as parity-associated in the mother and offspring have been shown to influence host metabolism in other systems, raising the possibility that such changes may influence host nutrient acquisition or utilization. These findings, taken together with our observation that even subtle differences in parity are associated with microbiome changes, underscore the importance of considering parity in the design and analysis of human microbiome studies during pregnancy and in infants.

microbiology↗

bioRxiv2020

Natural infection with Giardia is associated with altered community structure of the human and canine gut microbiome.

Enteric parasitic infections are among the most prevalent infections in lower- and middle-income countries (LMICs), and have a profound impact on global public health. While the microbiome is increasingly recognized as a key determinant of gut health and human development, the impact of naturally-acquired parasite infections on microbial community structure in the gut, and the extent to which parasite-induced changes in the microbiome may contribute to gastrointestinal symptoms, is poorly understood. Enteric parasites are routinely identified in companion animals in the United States, presenting a unique opportunity to leverage this animal model to investigate the impact of naturally-acquired parasite infections on the microbiome. Clinical, parasitological, and microbiome profiling of a cohort of 258 dogs revealed a significant correlation between parasite infection and composition of the bacterial community in the gut. Relative to other enteric pathogens, Giardia was associated with a more pronounced perturbation of the microbiome. Using a database mining approach that allowed us to compare our findings to a large-scale epidemiological study of enteric diseases in humans, we also observed a substantial alteration to microbiome structure in Giardia-infected children. Importantly, infection was associated with a reduction in the relative abundance of potential pathobionts, including Gammaproteobacteria, and an increase in Prevotella - a profile often associated with gut health. Taken together, our data show that widespread Giardia infection in young animals and humans is associated with significant remodeling of the gut microbiome, and provide a possible explanation for the high prevalence of asymptomatic Giardia infections observed across host species. ImportanceWhile enteric parasitic infections are among the most important infections in lower- and middle-income countries, their impact on gut microbiota is poorly understood. We reasoned that clinical symptoms associated with these infections may be influenced by alterations of the microbiome that occur during infection. To explore this notion, we took a two-pronged approach. First, we studied a cohort of dogs naturally infected with various enteric parasites and found a strong association between parasite infection and altered gut microbiota composition. Giardia, one of the most prevalent parasite infections globally, had a particularly large impact on the microbiome. Second, we took a database-driven strategy to integrate microbiome data with clinical data from large human field studies and found that Giardia infection is also associated with marked alteration of the gut microbiome of children, suggesting a possible explanation for why Giardia has been reported to be associated with protection from moderate-to-severe diarrhea.

microbiology↗

bioRxiv2019

Gut microbiome features associated with Clostridium difficile colonization in puppies

In people, colonization with Clostridium difficile, the leading cause of antibiotic-associated diarrhea, has been shown to be associated with distinct gut microbial features, including reduced bacterial community diversity and depletion of key taxa. In dogs, the gut microbiome features that define C. difficile colonization are less well understood. We sought to define the gut microbiome features associated with C. difficile colonization in puppies, a population where the prevalence of C. difficile has been shown to be elevated, and to define the effect of puppy age and litter upon these features and C. difficile risk. We collected fecal samples from weaned (n=27) and unweaned (n=74) puppies from 13 litters and analyzed the effects of colonization status, age and litter on microbial diversity using linear mixed effects models.\n\nColonization with C. difficile was significantly associated with younger age, and colonized puppies had significantly decreased bacterial community diversity and differentially abundant taxa compared to non-colonized puppies, even when adjusting for age. C. difficile colonization remained associated with decreased bacterial community diversity, but the association did not reach statistical significance in a mixed effects model incorporating litter as a random effect.\n\nEven though litter explained a greater proportion (67%) of the variability in microbial diversity than colonization status, we nevertheless observed heterogeneity in gut microbial community diversity and colonization status within more than half of the litters, suggesting that the gut microbiome contributes to colonization resistance against C. difficile. The colonization of puppies with C. difficile has important implications for the potential zoonotic transfer of this organism to people. The identified associations point to mechanisms by which C. difficile colonization may be reduced.

epidemiology↗

bioRxiv2017

MicrobiomeDB: a systems biology platform for integrating, mining and analyzing microbiome experiments.

MicrobiomeDB (http://microbiomeDB.org) is a data discovery and analysis platform that empowers researchers to fully leverage experimental variables to interrogate microbiome datasets. MicrobiomeDB was developed in collaboration with the Eukaryotic Pathogens Bioinformatics Resource Center (http://EuPathDB.org) and leverages the infrastructure and user interface of EuPathDB, which allows users to construct in silico experiments using an intuitive graphical strategy approach. The current release of the database integrates microbial census data with sample details for nearly 14,000 samples originating from human, animal and environmental sources, including over 9,000 samples from healthy human subjects in the Human Microbiome Project (http://portal.ihmpdcc.org/). Query results can be statistically analyzed and graphically visualized via interactive web applications launched directly in the browser, providing insight into microbial community diversity and allowing users to identify taxa associated with any experimental covariate.

microbiology↗

bioRxiv2017

Aging-associated dysbiosis increases susceptibility to enteric viral infection in Drosophila

Age is associated with increased susceptibility to enteric infections, but the molecular mechanisms are unclear. We find that aged Drosophila are more susceptible to enteric viral infections and that this increase in susceptibility is due to the aged microbiota, since depletion of the microbiota or reconstitution with a young microbiome suppressed infection. Metagenomic analysis of the aged microbiome revealed dysbiosis with an increased abundance in reactive oxygen species (ROS) producing pathways. This aged microbiota drives intestinal ROS production and we could restore immune function in old flies by reducing ROS genetically or pharmacologically. Moreover, we found that reconstitution of old flies with a cocktail of commensals, including L. fructivorans and heat-killed A. pomorum, could fully restore immunity. Altogether, these findings provide a mechanistic link between age-dependent dysbiosis and antiviral immunity and show that we can restore innate protection in aged animals, suggesting that this is a treatable and reversible state.

immunology↗