Publications by authors named "Eric J Alm"

Sequence alignment is foundational to many bioinformatic analyses. Many aligners start by splitting sequences into contiguous, fixed-length seeds, called k-mers. Alignment is faster with longer, unique seeds, but more accurate with shorter seeds avoiding mutations.

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Host-parasite relationships drive the evolution of both parties. In microbe-phage dynamics, CRISPR functions as an adaptive defense mechanism, updating immunity via spacer acquisition. Here, we investigated these interactions within the human gut microbiome, uncovering low frequencies of spacer acquisition at an average rate of one spacer every ∼2.

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Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC).

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Among dozens of microbial DNA modifications regulating gene expression and host defense, phosphorothioation (PT) is the only known backbone modification, with sulfur inserted at a non-bridging oxygen by and gene families. Here we explored the distribution of PT genes in 13,663 human gut microbiome genomes, finding that 6.3% possessed or genes predominantly in Bacillota, Bacteroidota, and Pseudomonadota.

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Background: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically-reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by and gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome.

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Background: Accurate identification of genetic variants, such as point mutations and insertions/deletions (indels), is crucial for various genetic studies into epidemic tracking, population genetics, and disease diagnosis. Genetic studies into microbiomes often require processing numerous sequencing datasets, necessitating variant identifiers with high speed, accuracy, and robustness.

Results: We present QuickVariants, a bioinformatics tool that effectively summarizes variant information from read alignments and identifies variants.

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Introduction: Proton pump inhibitor (PPI) use has been associated with an increased risk of gastrointestinal and upper respiratory infections in children. There are limited longitudinal data on the effect of PPI in children. The goal of this prospective observational study was to compare the stool and oropharyngeal microbiome of children before and after starting PPIs.

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Article Synopsis
  • Scientists created a special system called GuMI to study how gut microbes like F. prausnitzii interact with human immune cells and gut lining cells over a long time.
  • They found that immune cells called antigen-presenting cells (APCs) helped increase the levels of certain signaling molecules when present in the system with the gut lining and microbes.
  • The presence of CD4 naive T cells changed how the gut lining reacted to the microbes, showing that different immune cells play important roles in controlling how the gut responds to good bacteria and possible inflammation.
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Increasing levels of industrialization have been associated with changes in gut microbiome structure and loss of features thought to be crucial for maintaining gut ecological balance. The stability of gut microbial communities over time within individuals seems to be largely affected by these changes but has been overlooked among transitioning populations from low- to middle-income countries. Here, we used metagenomic sequencing to characterize the temporal dynamics in gut microbiomes of 24 individuals living an urban non-industrialized lifestyle in the Brazilian Amazon.

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Members of microbial communities can substantially overlap in substrate use. However, what enables functionally redundant microorganisms to coassemble or even stably coexist remains poorly understood. Here, we show that during unstable successional dynamics on complex, natural organic matter, functionally redundant bacteria can coexist by partitioning low-concentration substrates even though they compete for one simple, dominant substrate.

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Microbial systems appear to exhibit a relatively high switching capacity of moving back and forth among few dominant communities (taxon memberships). While this switching behavior has been mainly attributed to random environmental factors, it remains unclear the extent to which internal community dynamics affect the switching capacity of microbial systems. Here, we integrate ecological theory and empirical data to demonstrate that structured community transitions increase the dependency of future communities on the current taxon membership, enhancing the switching capacity of microbial systems.

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Community assembly describes how different ecological processes shape microbial community composition and structure. How environmental factors impact community assembly remains elusive. Here we sampled microbial communities and >200 biogeochemical variables in groundwater at the Oak Ridge Field Research Center, a former nuclear waste disposal site, and developed a theoretical framework to conceptualize the relationships between community assembly processes and environmental stresses.

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Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we establish a gut epithelium-microbe-immune microphysiological system to maintain the long-term continuous co-culture of with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), with CD4 naïve T cells circulating underneath the colonic epithelium.

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Soluble human lectins are critical components of innate immunity. Genetic models suggest that lectins influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins' roles in regulating microbiota requires an understanding of which microbial species they bind within native communities.

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Wastewater surveillance (WWS) has been globally recognised to be a useful tool in quantifying SARS-CoV-2 RNA at the community and residential levels without biases associated with case-reporting. The emergence of variants of concern (VOCs) have given rise to an unprecedented number of infections even though populations are increasingly vaccinated. This is because VOCs have been reported to possess higher transmissibility and can evade host immune responses.

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Background: Fecal Microbiota Transplant (FMT) has proven effective in treating recurrent infection (rCDI) and has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. However, there is little known regarding predictors of engraftment.

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SARS-CoV-2 wastewater-based surveillance (WBS) offers a tool for cost-effective oversight of a population's infections. In the past two years, WBS has proven to be crucial for managing the pandemic across different geographical regions. However, the changing context of the pandemic due to high levels of COVID-19 vaccination warrants a closer examination of its implication towards SARS-CoV-2 WBS.

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Wastewater-based epidemiology has emerged as a promising technology for population-level surveillance of COVID-19. In this study, we present results of a large nationwide SARS-CoV-2 wastewater monitoring system in the United States. We profile 55 locations with at least six months of sampling from April 2020 to May 2021.

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The metagenome embedded in urban sewage is an attractive new data source to understand urban ecology and assess human health status at scales beyond a single host. Analyzing the viral fraction of wastewater in the ongoing COVID-19 pandemic has shown the potential of wastewater as aggregated samples for early detection, prevalence monitoring, and variant identification of human diseases in large populations. However, using census-based population size instead of real-time population estimates can mislead the interpretation of data acquired from sewage, hindering assessment of representativeness, inference of prevalence, or comparisons of taxa across sites.

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Clinical testing has been the cornerstone of public health monitoring and infection control efforts in communities throughout the COVID-19 pandemic. With the anticipated reduction of clinical testing as the disease moves into an endemic state, SARS-CoV-2 wastewater surveillance (WWS) will have greater value as an important diagnostic tool. An in-depth analysis and understanding of the metrics derived from WWS is required to interpret and utilize WWS-acquired data effectively (McClary-Gutierrez et al.

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Maternal microbial dysbiosis has been implicated in adverse postnatal health conditions in offspring, such as obesity, cancer, and neurological disorders. We observed that the progeny of mice fed a Westernized diet (WD) with low fiber and extra fat exhibited higher frequencies of stereotypy, hyperactivity, cranial features and lower FMRP protein expression, similar to what is typically observed in Fragile X Syndrome (FXS) in humans. We hypothesized that gut dysbiosis and inflammation during pregnancy influenced the prenatal uterine environment, leading to abnormal phenotypes in offspring.

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Arboviral diseases are caused by a group of viruses spread by the bite of infected arthropods. Amongst these, dengue, Zika, west nile fever and yellow fever cause the greatest economic and social impact. Arboviral epidemics have increased in frequency, magnitude and geographical extent over the past decades and are expected to continue increasing with climate change and expanding urbanisation.

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The microbiome contributes to the development and maturation of the immune system. In response to commensal bacteria, intestinal CD4 T lymphocytes differentiate into functional subtypes with regulatory or effector functions. The development of small intestine intraepithelial lymphocytes that coexpress CD4 and CD8αα homodimers (CD4IELs) depends on the microbiota.

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