About

Michael Fischbach is the Liu (Liao) Family Professor of Bioengineering at Stanford University, an Institute Scholar of Stanford ChEM-H, and the director of the Stanford Microbiome Therapies Initiative. His laboratory studies the mechanisms of microbiome-host interactions. Fischbach received his Ph.D. in chemistry from Harvard in 2007 as a John and Fannie Hertz Foundation Fellow, where he studied the role of iron acquisition in bacterial pathogenesis and the biosynthesis of antibiotics. After two years as an independent fellow at Massachusetts General Hospital, he joined the faculty at UCSF, where he founded his lab before moving to Stanford in 2017. Fischbach is a recipient of numerous awards including the NIH Director's Pioneer and New Innovator Awards, an HHMI-Simons Faculty Scholars Award, a Fellowship from the David and Lucile Packard Foundation, a Medical Research Award from the W.M. Keck Foundation, a Burroughs Wellcome Fund Investigators award, and the Vannevar Bush Faculty Fellowship. He is also a co-founder of Revolution Medicines and Kelonia, and a co-founder and director of Azalea. Additionally, he serves on the scientific advisory boards of the Chan Zuckerberg Initiative, Stand Up to Cancer, and TCG Labs/Soleil Labs, and is an innovation partner at The Column Group.

Research topics

• Biology
• Microbiology
• Immunology
• Genetics
• Biochemistry
• Bioinformatics
• Medicine
• Internal medicine
• Endocrinology
• Ecology
• Pharmacology
• Virology
• Cancer research
• Computational biology

Selected publications

• Microbiota and kidney disease: the road ahead

  Nature Reviews Nephrology · 2025-07-28 · 19 citations

  reviewOpen access
  PublisherOA PDFDOI

• Gut microbe-derived short-chain fatty acids regulate joint inflammation and activation of infiltrating and resident myeloid cells after alphavirus infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-03

  articleOpen access

  SUMMARY Although oral antibiotics can predispose to joint inflammation, this phenomenon remains poorly understood. Here, we leverage mouse models of alphavirus-induced arthritis to investigate the roles of gut commensals, metabolites, and host immune mechanisms in promoting musculoskeletal inflammation. Mice treated with a short course of oral antibiotics exhibited worsened arthritis after chikungunya (CHIKV) or Mayaro virus infections. This phenotype was associated with loss of short chain fatty acids (SCFA), greater intestinal permeability, and activation of gut-associated immune cells, and required TLR4 signaling, MyD88 expression, monocytes, antigen-specific and bystander CD4 + T cells, and pro-inflammatory cytokines. Administration of exogenous SCFA or colonization of mice with bacterial species that generate SCFA mitigated CHIKV-induced joint inflammation. Single-cell RNA sequencing revealed that gut-derived SCFA ameliorate the inflammatory phenotype of synovial CD4 + T cells, infiltrating monocytes, and resident osteoclast-like cells. Thus, antibiotic-triggered gut dysbiosis exacerbates alphavirus arthritis by shaping the inflammatory profile of both infiltrating and resident immune cells in joint tissues.

  PublisherOA PDFDOI

• A gut pathobiont regulates circulating glycine and host metabolism in a twin study comparing vegan and omnivorous diets

  medRxiv · 2025-01-12 · 2 citations

  preprintOpen access

  Summary Metabolic diseases including type 2 diabetes and obesity pose a significant global health burden. Plant-based diets, including vegan diets, are linked to favorable metabolic outcomes, yet the underlying mechanisms remain unclear. In a randomized trial involving 21 pairs of identical twins, we investigated the effects of vegan and omnivorous diets on the host metabolome, immune system, and gut microbiome. Vegan diets induced significant shifts in serum and stool metabolomes, cytokine profiles, and gut microbial composition. Despite lower dietary glycine intake, vegan diet subjects exhibited elevated serum glycine levels linked to reduced abundance of the gut pathobiont Bilophila wadsworthia . Functional studies demonstrated that B. wadsworthia metabolizes glycine via the glycine reductase pathway and modulates host glycine availability. Removing B. wadsworthia from a complex microbiota in mice elevated glycine levels and improved metabolic markers. These findings reveal a previously underappreciated mechanism by which diet regulates host metabolic status via the gut microbiota.

  PublisherOA PDFDOI

• Systematic identification and characterization of regulators of aryl hydrocarbon receptor signaling

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-16 · 1 citations

  preprintOpen access

  The human aryl hydrocarbon receptor (AHR) integrates chemical signals derived from the environment, gut microbes, and endogenous sources to regulate processes ranging from intestinal barrier integrity to xenobiotic detoxification. Despite strong evidence that dysregulation of AHR signaling is a causal factor in metabolic and autoimmune disorders, we currently lack a comprehensive understanding of the factors that regulate AHR activity in human cells. Here, we use genome-scale CRISPR screening to systematically identify regulators of AHR signaling in hepatocytes. The resulting datasets recapitulate the core AHR signaling pathway and identify a large network of regulators. Many of these factors have roles beyond AHR signaling, reflecting that AHR signaling is deeply integrated into human cell biology. We further dissect this network to reveal novel modes of regulation of AHR expression, protein levels, and signaling. For example, we find that the E3 ubiquitin ligase UBR5 sustains AHR signaling by counteracting degradation of ligand-bound AHR. Finally, we identify components of the AHR regulatory network that are specific to cell types and ligands as potential nodes to manipulate AHR signaling in a targeted manner for therapeutic benefit. Overall, our results define the regulatory network that underpins AHR activation, with implications for our understanding of host-microbe interactions and integrative chemosensation and the etiology of metabolic and inflammatory disorders.

  PublisherOA PDFDOI

• 1105: A SHIFT IN GUT MICROBIAL COMMUNITY ALTERS ANTIGEN-SPECIFIC REGULATORY T CELLS AND DISEASE PHENOTYPE IN A MODEL OF FOOD ALLERGY

  Gastroenterology · 2025-05-01

  articleSenior author
  PublisherDOI

• Publisher Correction: Skin autonomous antibody production regulates host–microbiota interactions

  Nature · 2025-02-19 · 3 citations

  erratumOpen access
  PublisherOA PDFDOI

• Gut microbial composition modulates food-specific CD4 ⁺ T cells in food allergy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-28

  preprintOpen access

  Abstract The growing food allergy epidemic is thought to be related to changing environmental factors, particularly changes in the gut microbiome. While prior work has demonstrated that food allergy can be modulated by gut microbes, little is known about how food allergen-specific CD4 + T cells are affected by gut microbial composition. Here, we report that food allergy severity differs between mice obtained from two different specific pathogen-free mouse vendors (Jackson Labs [Jax] and Taconic Biosciences [Tac]). Mice from Tac develop diarrhea and anaphylaxis after fewer allergen exposures than mice from Jax. Using food allergen peptide:MHCII tetramers, we also find that Tac mice have fewer allergen-specific regulatory T cells in the small intestine compared to mice from Jax. In addition, Tac mice have a greater abundance of small intestinal mucosal mast cells and increased intestinal permeability. The increased food allergy severity phenotype is transferable via co-housing, which corresponds to a shift in Jax microbial communities towards those found in Tac mice. Our findings demonstrate for the first time that food allergen-specific Treg cells can be modulated by gut microbial community composition, which in turn is correlated to food allergy severity.

  PublisherOA PDFDOI

• A Gut Pathobiont Regulates Circulating Glycine and Host Metabolism in a Twin Study Comparing Vegan and Omnivorous Diets

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• A shift in gut microbial community alters antigen-specific regulatory T cells and disease phenotype in a model of food allergy 3125

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description The intestinal immune system must handle the conundrum of maintaining barrier function in the face of a dense and complex microbial community, while allowing uptake of and tolerance to food. However, little is known about the influence of gut microbes on immune responses to food antigens. We identified substantial differences in a food allergy model in mice with distinct fecal microbial communities. Mice from either Jackson (Jax) or Taconic (Tac) vendors were sensitized via injection of ovalbumin (OVA) plus alum. Two weeks after sensitization, mice underwent oral gavage every 2-3 days with OVA. Allergic response was marked by production of profuse watery stool within 60 minutes following gavage. After 3 gavages, 74% of Tac mice developed diarrhea compared to 23% of Jax mice. In the small intestine, Tac mice had significantly fewer OVA-specific regulatory T cells and significantly more mucosal mast cells. Tac and Jax mice had substantially different stool bacterial communities as determined by shotgun metagenomic sequencing. However when mice were cohoused prior to OVA sensitization, Jax mice had stool communities resembling those from Tac and developed diarrhea at the same rate as Tac animals. We found that shifts in bacterial communities led to changes in allergen-specific CD4+ T cells, mucosal mast cells, and severity of food allergy. Ultimately, these findings can help us understand why certain individuals develop food allergy and might lead to new therapies. Funding Sources ARW is supported by the Life Science Research Foundation and Open Philanthropy. Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

• Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors

  Nature Communications · 2024-08-06 · 34 citations

  articleOpen access

  Allosteric modulation is a central mechanism for metabolic regulation but has yet to be described for a gut microbiota-host interaction. Phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, has previously been clinically associated with and mechanistically linked to cardiovascular disease (CVD) and heart failure (HF). Here, using cells expressing β1- versus β2-adrenergic receptors (β1AR and β2AR), PAGln is shown to act as a negative allosteric modulator (NAM) of β2AR, but not β1AR. In functional studies, PAGln is further shown to promote NAM effects in both isolated male mouse cardiomyocytes and failing human heart left ventricle muscle (contracting trabeculae). Finally, using in silico docking studies coupled with site-directed mutagenesis and functional analyses, we identified sites on β2AR (residues E122 and V206) that when mutated still confer responsiveness to canonical β2AR agonists but no longer show PAGln-elicited NAM activity. The present studies reveal the gut microbiota-obligate metabolite PAGln as an endogenous NAM of a host GPCR. Allosteric modulation is crucial in metabolic regulation but unexplored in gut microbehost interactions. Here the authors show gut microbe-derived phenylacetylglutamine acts as a negative allosteric modulator of β2-adrenergic receptors, impacting heart function.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01DK11017404

  NIH · $353k · 2020

• Core B: Analytical & Synthetic Chemistry Core

  NIH · $21.8M · 2019–2025

• NIH Grant M01RR001346

  NIH · $469k · 2008

• NIH Grant R01DK110174

  NIH · $1.1M · 2020

• Dietary and Microbial Reprogramming of Intestinal Microbiota-Produced Metabolites

  NIH · $6.5M · 2014–2026

Frequent coauthors

• Christopher T. Walsh

  Met Office

  61 shared

• Norman Talal

  59 shared

• Justin L. Sonnenburg

  Chan Zuckerberg Initiative (United States)

  59 shared

• Kazuki Nagashima

  Stanford University

  46 shared

• Stanley L. Hazen

  Cleveland Clinic Lerner College of Medicine

  35 shared

• Marnix H. Medema

  Wageningen University & Research

  34 shared

• Steven K. Higginbottom

  Stanford University

  34 shared

• Yasmine Belkaid

  National Institute of Allergy and Infectious Diseases

  33 shared

Education

• Ph.D., Bioengineering

  Stanford University

  2006

• M.S., Bioengineering

  University of California, San Diego

  2001

• B.S., Bioengineering

  University of California, San Diego

  1999

Awards & honors

• NIH Director's Pioneer and New Innovator Awards
• HHMI-Simons Faculty Scholars Award
• Fellowship for Science and Engineering from the David and Lu…
• Medical Research Award from the W.M. Keck Foundation
• Burroughs Wellcome Fund Investigators in the Pathogenesis of…