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Eric J. Alm

Eric J. Alm

· ProfessorVerified

Massachusetts Institute of Technology · Civil & Environmental Engineering

Active 1998–2026

h-index125
Citations78.1k
Papers527198 last 5y
Funding$2.2M
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About

Eric J. Alm is a professor at the Massachusetts Institute of Technology in the Department of Civil and Environmental Engineering. His research group employs both computational/theoretical and experimental approaches to understand the evolution of microorganisms, emphasizing a systems-level perspective. His areas of special interest include tools for detecting natural selection in microbes, the evolutionary origin of gene families, mining metagenomic sequence data, experimental evolution of microbes, modeling bacterial ecology, gene regulatory networks in bacteria, and protein structure and design. Professor Alm has a diverse academic background, holding a B.S. from the University of Illinois, Urbana, an M.S. from the University of California, Riverside, and a Ph.D. from the University of Washington, Seattle. He completed a postdoctoral fellowship at the University of California, Berkeley, and Lawrence Berkeley National Laboratory. He has enjoyed teaching a variety of classes at MIT, covering microbiology, computer algorithms, and thermodynamics of biomolecules, and is currently looking forward to teaching a new class on microbial evolution and genetics.

Research topics

  • Biology
  • Genetics
  • Computer Science
  • Microbiology
  • Computational biology
  • Virology
  • Environmental engineering
  • Artificial Intelligence
  • Environmental science
  • Data Mining
  • Machine Learning
  • Medicine
  • Cell biology
  • Ecology
  • Internal medicine
  • Environmental planning
  • Evolutionary biology
  • Immunology
  • Environmental health
  • Bioinformatics

Selected publications

  • Mapping population immunity: How protease and antibody fragmentation shape wastewater findings

    Water Research · 2026-02-12

    article
  • <i>Blautia wexlerae</i> Transforms Dietary Fatty Acids to Activate Enteroendocrine Signaling and Improve Metabolic Health in Mice and Humans

    bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-14

    articleOpen accessSenior author

    ABSTRACT Metabolites produced by the gut microbiome influence host metabolic health, but how this occurs remains incompletely defined. Here, we report that a common human gut commensal, Blautia wexlerae , converts dietary fats into bioactive metabolites that induce gut hormone production to affect glucose metabolism and suppress appetite. We found that colonization with Blautia wexlerae correlated with healthier eating behaviors in humans. Blautia wexlerae encodes a unique acyl transferase and is capable of producing acyl amines from nutrient substrates. These Blautia acyl amines stimulated human enteroendocrine cells to secrete GLP-1 and other gut peptide hormones more potently than endogenously produced acyl amines. When fed to mice, acyl amines improved glycemic control and decreased appetite. In humans, higher stool levels of Blautia DNA encoding acyl amine synthesis genes correlated with leanness and decreased dietary fat intake. These results define a mechanism of action for how Blautia wexlerae affects host metabolic control.

  • An integrated framework for early detection and transmissibility assessment of emerging variants in wastewater

    International Journal of Hygiene and Environmental Health · 2026-04-02

    article
  • Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome

    Microbiome · 2025-03-24 · 1 citations

    articleOpen access

    Abstract 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 dnd and ssp 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. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications. Results Exploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5–10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m 6 dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor’s Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Bacillota (formerly Firmicutes), Actinomycetota (formerly Actinobacteria), and Pseudomonadota (formerly Proteobacteria), which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies. Conclusions The results of our studies provide a benchmark for understanding the behavior of an abundant and chemically reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.

  • Host transcriptional responses to gut microbiome variation arising from urbanism

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-26

    preprintOpen access

    ABSTRACT Gut microbiomes of urban communities are compositionally different from their rural counterparts, and are associated with immune dysregulation and gastrointestinal disease. However, it is unknown whether these compositional differences impact host physiology, and through what mechanisms. Here, we used human colonic epithelial cells to directly compare host transcriptional changes induced by gut microbiomes from urban versus rural communities. We co-cultured host cells with live, stool-derived gut microbiomes from Rwanda, Ghana, Nigeria, Malaysia, and the United States, and quantified transcriptional responses using RNA-seq. We found that urban microbiomes affected innate immune pathways, including TNF signaling and bacterial antigen recognition. We also found that high-diversity microbiomes elicited a stronger host transcriptional response, while low-diversity microbiomes triggered epithelial restructuring and glycolysis. Finally, specific taxa driving these effects, including Bifidobacterium adolescentis and Bacteroides dorei , correlated with lifestyle factors such as diet. These findings demonstrate that urbanization-associated microbiome changes directly influence host epithelial gene expression.

  • Convergent genomic responses of human gut bacteria to variations in industrialization

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-20 · 2 citations

    preprintOpen access

    To what extent gut bacteria respond to the distinct ecological pressures imposed by human lifestyle remains unclear. Here, we investigate how genomic adaptation in gut bacteria differ between industrialized and non-industrialized human populations. We generated a broad collection of isolate genomes spanning diverse host geographies, lifestyles, species, and strains. We first found that compared to MAGs, paired isolate genomes recover more functional elements and signals of horizontal gene transfers (HGTs). Leveraging isolate genomes from multiple species, we find that strains from industrialized hosts experience an expansion of proteome size and harbor greater pangenome fluidity, driven by recent events of HGTs. Gene- and variant-level analyses reveal convergent patterns of lifestyle-specific adaptation in functions that are critical for ecological adaptation, such as stress response, cell envelope remodeling and central metabolism. Our results demonstrate that industrialization imprints evolutionary signatures on gut bacterial genomes, illuminating the effects of rapidly changing environments on human biology.

  • Author Correction: X-Mapper: fast and accurate sequence alignment via gapped x-mers

    Genome biology · 2025-01-27

    erratumOpen access
  • <i>Bifidobacterium longum</i> subsp. <i>nexti</i> subsp. nov., a novel subspecies isolated from infant stool

    bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-23 · 1 citations

    preprint

    Abstract Bifidobacterium species are well-established members of the human gut microbiome, particularly prominent during infancy, contributing to host health. Within this genus, Bifidobacterium longum ( BL. ) is a widespread species found in both infant and adult guts, known for its complexity and functional diversity among its known subspecies: BL. longum , BL. infantis and BL. suis . Here, using genomic and phylogenetic tools we propose a novel subspecies within the BL. species, Bifidobacterium longum subsp. nexti subspecies novel. We analyzed 435 BL. genomes using a polyphasic taxonomic approach comprising average nucleotide identity (ANI), digital DNA–DNA hybridization (dDDH), and pangenome analysis. We identified nine BL. strains, isolated from human infants and adults stool samples, as members of a distinct lineage within the BL. species. The type strain, LL6991, was isolated from the stool of a two-week-old Dutch infant in the Lifelines NEXT birth cohort. Phenotypically, BL. nexti exhibits a distinct morphological pattern, predominantly forming rod-shaped cells, often in chains with visible septa, contrasting with the Y-shaped morphology commonly observed for other BL. subspecies. Furthermore, BL. nexti demonstrates unique metabolic capabilities, including efficient utilization of fructose, and starch, carbohydrates not metabolized well by other tested BL. subspecies. This ability may be attributed to specific genes, such as a gene predicted to encode an extracellular amylopullulanase. This characterization expands the known diversity within the BL. species and provides insights into BL. nexti ’s unique adaptations and potential ecological roles within the human gut, especially in infants. Based on the consistent results from genotypic, phylogenetic, and phenotypic analyses, a novel subspecies with the name Bifidobacterium longum subsp. nexti , with type strain LL6991 (=NCCB 101085 =DSM 120337), is proposed.

  • Gut microbiota profiles of peninsular Malaysian populations are associated with urbanization and lifestyle

    Scientific Reports · 2025-07-05 · 6 citations

    articleOpen access

    There is increasing evidence of distinct gut microbiome compositions between populations living industrialized and non-industrialized lifestyles worldwide. However, whether populations of Malaysia exhibit variations in their microbiome, and to what extent host lifestyle correlates with these variations, remains unclear. Malaysia's extensive geographical and sociocultural diversity provides a unique opportunity to explore how lifestyle and environmental exposures are associated with the human gut microbiome. Here, we characterized the gut microbiome of three populations in peninsular Malaysia, each representing different lifestyle contexts, and identified host factors associated with microbiome variation. Our findings suggest that lifestyle-related factors are strongly associated with differences in microbial community composition across populations. In particular, urban and rural individuals harbor gut microbiota with distinct community structures. We further identified specific taxa as potential microbial signatures of host lifestyle, with the genera Prevotella and Cryptobacteroides enriched in rural populations, while Phocaeicola, Vescimonas, and Megasphaera were more prevalent among urban individuals. In addition to lifestyle, demographic factors such as age, sex, and BMI were also associated with variation in the gut microbiome. This study highlights the influence of urbanization, lifestyle, and diet on the gut microbiome landscape of Malaysian populations and underscores the importance of considering sociocultural context in future microbiome research.

  • Modest functional diversity decline and pronounced composition shifts of microbial communities in a mixed waste-contaminated aquifer

    Microbiome · 2025-04-28 · 5 citations

    articleOpen access

    BACKGROUND: Microbial taxonomic diversity declines with increased environmental stress. Yet, few studies have explored whether phylogenetic and functional diversities track taxonomic diversity along the stress gradient. Here, we investigated microbial communities within an aquifer in Oak Ridge, Tennessee, USA, which is characterized by a broad spectrum of stressors, including extremely high levels of nitrate, heavy metals like cadmium and chromium, radionuclides such as uranium, and extremely low pH (< 3). RESULTS: Both taxonomic and phylogenetic α-diversities were reduced in the most impacted wells, while the decline in functional α-diversity was modest and statistically insignificant, indicating a more robust buffering capacity to environmental stress. Differences in functional gene composition (i.e., functional β-diversity) were pronounced in highly contaminated wells, while convergent functional gene composition was observed in uncontaminated wells. The relative abundances of most carbon degradation genes were decreased in contaminated wells, but genes associated with denitrification, adenylylsulfate reduction, and sulfite reduction were increased. Compared to taxonomic and phylogenetic compositions, environmental variables played a more significant role in shaping functional gene composition, suggesting that niche selection could be more closely related to microbial functionality than taxonomy. CONCLUSIONS: Overall, we demonstrated that despite a reduced taxonomic α-diversity, microbial communities under stress maintained functionality underpinned by environmental selection. Video Abstract.

Recent grants

Frequent coauthors

  • Janelle R. Thompson

    Singapore Centre for Environmental Life Sciences Engineering

    229 shared
  • Xiaoqiong Gu

    National University of Singapore

    165 shared
  • Wei Lin Lee

    Singapore-HUJ Alliance for Research and Enterprise

    163 shared
  • Federica Armas

    Singapore-MIT Alliance for Research and Technology

    143 shared
  • Adam P. Arkin

    University of California, Berkeley

    126 shared
  • Hongjie Chen

    Nanfang Hospital

    123 shared
  • Franciscus Chandra

    115 shared
  • Ramnik J. Xavier

    Broad Institute

    106 shared

Education

  • Ph.D., Microbiology

    Massachusetts Institute of Technology

    1994
  • B.S., Microbiology

    University of California, Berkeley

    1989
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