About

Robert Kerby is an Honorary Associate in the Department of Bacteriology at the University of Wisconsin-Madison. He is associated with the Rey Lab and is located in the Microbial Sciences Building at Madison, WI. His contact information includes a phone number (608) 890-2366 and an email address rlkerby@wisc.edu. As an Honorary Associate, he contributes to the department's academic and research activities, although specific details about his research focus, background, or key contributions are not provided on the page.

Research topics

• Microbiology
• Biology
• Biochemistry
• Genetics
• Mathematics
• Zoology
• Cell biology

Selected publications

• Investigation of bile salt hydrolase activity in human gut bacteria reveals production of conjugated secondary bile acids

  Nature Communications · 2026-02-23 · 1 citations

  articleOpen access

  Through biochemical transformation of host-derived bile acids, gut bacteria mediate host-microbe crosstalk and function at the interface of nutrition and host metabolic regulation. Bile acids play a crucial role in human health by facilitating the absorption of dietary lipophilic nutrients, interacting with hormone receptors to regulate host physiology, and shaping gut microbiota composition through antimicrobial activity. Bile acids deconjugation by bacterial bile salt hydrolase has long been recognized as the first necessary bile acid modification required before further transformations can occur. Here, we show that bile salt hydrolase activity is common among human gut bacterial isolates spanning seven major phyla. However, we observed variation in both the extent and the specificity of deconjugation of bile acids among the tested taxa. Unexpectedly, we discovered that certain strains were capable of directly dehydrogenating conjugated bile acids via hydroxysteroid dehydrogenases to produce conjugated secondary bile acids both in vitro and in vivo. These results challenge the prevailing notion that deconjugation is a prerequisite for further bile acid modifications and lay a foundation for new hypotheses regarding how bacteria act individually or in concert to diversify the bile acid pool and influence host physiology. Here, the authors show that bile salt hydrolase activity is common among human gut bacterial isolates spanning seven major phyla and identify strains capable of directly dehydrogenating conjugated bile acids via hydroxysteroid dehydrogenases to produce conjugated secondary bile acids, challenging the notion that deconjugation is a prerequisite for further bile acid modifications.

  PublisherOA PDFDOI

• Author Correction: Gut microbiota strain richness is species specific and affects engraftment

  Nature · 2025-01-28

  erratumOpen access
  PublisherOA PDFDOI

• Fecal Short-Chain Fatty Acids Vary by Sex and Amyloid Status

  medRxiv · 2025-08-01 · 1 citations

  preprintOpen access

  INTRODUCTION: Short-chain fatty acids (SCFAs), produced by gut microbes, influence Alzheimer's disease (AD) pathology in animals. Less is known about SCFAs and AD in humans. We profiled feces of adults along the AD continuum to investigate gut microbiome and SCFA associations with AD pathology and cognition. METHODS: We measured SCFAs and bacterial abundances in fecal samples from 287 participants in the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention. We performed regressions examining associations between SCFAs or gut microbes and AD pathology and cognition. RESULTS: Fecal propionate, isovalerate, and propionate-producing bacteria are inversely associated with amyloid status. Mediation analysis found that propionate mediates sex-specific associations between SCFAs and CSF biomarkers. SCFA levels are associated with slower cognitive decline. DISCUSSION: These results link SCFAs and propionate-producing bacteria with AD. This may inform efforts to leverage diet and specific bacteria to boost SCFA production and potentially ameliorate AD progression.

  PublisherOA PDFDOI

• Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis

  npj Biofilms and Microbiomes · 2025-01-10 · 27 citations

  articleOpen access

  Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid. Levels of these metabolites were negatively associated with atherosclerosis burden. Furthermore, we show that 3,4-DHBA prevented lipopolysaccharide (LPS)-induced decrease in transendothelial electrical resistance (TEER). These results suggest that the effects of quercetin on atherosclerosis are influenced by gut microbes and are potentially mediated by bacterial metabolites derived from the flavonoid.

  PublisherOA PDFDOI

• Fecal levels of short‐chain fatty acids and prominent bacterial taxa involved in their production are inversely associated with amyloid‐positive status

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  BACKGROUND: Short-chain fatty acids (SCFA), including acetate, propionate, and butyrate, are abundant gut bacterial metabolites produced via the fermentation of dietary fibers and resistant starch. Several lines of evidence, particularly in preclinical mouse models, suggest a protective role of SCFA against Alzheimer's Disease (AD) pathology. In one study, supplementation of mice with tributyrin, a butyrate prodrug, significantly attenuated AD pathology. However, the relationships between SCFA, the bacterial taxa that produce them, and AD biomarkers require further elucidation in humans. METHOD: We assessed gut metagenomes and SCFA levels in fecal samples from 213 cognitively unimpaired Microbiome Alzheimer's Risk Study (MARS) participants (Table 1). The cohort was co-enrolled in the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention, which track preclinical disease progression in middle-aged and older adults at risk for AD. We sequenced DNA extracted from 213 fecal samples (one sample per participant, 30 million reads per sample), created metagenome-assembled genomes (MAGs), and annotated their functions. We measured levels of the major SCFA in fecal samples using headspace gas chromatography. We performed multiple linear regressions between levels of cerebrospinal fluid (CSF) AD biomarkers and each SCFA or MAG, controlling for age, sex, body mass index, and APOE genotype. RESULT: We found an inverse association between amyloid positive status (CSF Aꞵ42/Aꞵ40 <0.046) and MAGs encoding propionate or butyrate production pathways. Fecal acetate, propionate, and butyrate levels were reduced in females and in participants with amyloid-positive status. Mediation analysis detected a trend indicating that butyrate may mediate the inverse relationship between MAGs with butyrate production pathways and amyloid positive status. CONCLUSION: Relative abundances of MAGs encoding enzymes for propionate and butyrate production were reduced in amyloid-positive participants in a cognitively unimpaired human cohort enriched for AD risk. These results, combined with the extensive literature in preclinical AD mouse models, suggest that SCFA may play a causal role in AD progression.

  PublisherOA PDFDOI

• The Central Role of Gut Microbes in Host Purine Homeostasis

  Annual Review of Microbiology · 2025-09-03 · 1 citations

  reviewOpen access

  Purines are ubiquitous metabolites that play evolutionarily conserved roles, including as precursors to molecules central to life. Purine synthesis is metabolically and energetically expensive; thus, under physiological conditions, intermediates of purine degradation are efficiently reused through salvage pathways. Excess purines are oxidized and eliminated via the kidneys and intestine. The efficient elimination of excess purines in humans is critical because the primary waste product of purine metabolism, uric acid, is proinflammatory and has been linked to multiple health conditions. Recent studies suggest that gut bacteria influence the purine pool locally and systemically. Bacteria can break down uric acid and other purines aerobically and anaerobically and may regulate their homeostasis. In this article, we provide an overview of purines and their metabolism, and we discuss our current understanding of the complex purine-dependent cross talk and cross-feeding between the host and the gut microbiome.

  PublisherDOI

• Investigation of Bile Salt Hydrolase Activity in Human Gut Bacteria Reveals Production of Conjugated Secondary Bile Acids

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-16 · 10 citations

  preprintOpen access

  Through biochemical transformation of host-derived bile acids (BAs), gut bacteria mediate host-microbe crosstalk and sit at the interface of nutrition, the microbiome, and disease. BAs play a crucial role in human health by facilitating the absorption of dietary lipophilic nutrients, interacting with hormone receptors to regulate host physiology, and shaping gut microbiota composition through antimicrobial activity. Bile acid deconjugation by bacterial bile salt hydrolase (BSH) has long been recognized as the first necessary BA modification required before further transformations can occur. Here, we show that BSH activity is common among human gut bacterial isolates spanning seven major phyla. We observed variation in both the extent and the specificity of deconjugation of BAs among the tested taxa. Unexpectedly, we discovered that certain strains were capable of directly dehydrogenating conjugated BAs via hydroxysteroid dehydrogenases (HSD) to produce conjugated secondary BAs. These results challenge the prevailing notion that deconjugation is a prerequisite for further BA modifications and lay a foundation for new hypotheses regarding how bacteria act individually or in concert to diversify the BA pool and influence host physiology.

  PublisherDOI

• Fecal short‐chain fatty acids vary by sex and amyloid status

  Alzheimer s & Dementia · 2025-11-01 · 4 citations

  articleOpen access

  Abstract INTRODUCTION Short‐chain fatty acids (SCFAs), produced by gut microbes, influence Alzheimer's disease (AD) pathology in animals. Less is known about SCFAs and AD in humans. We profiled feces of adults along the AD continuum to investigate gut microbiome and SCFA associations with AD pathology and cognition. METHODS We measured SCFAs and bacterial abundances in fecal samples from 287 participants in the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention. We performed regressions examining associations between SCFAs or gut microbes and AD pathology and cognition. RESULTS Fecal propionate, isovalerate, and propionate‐producing bacteria are inversely associated with amyloid status. Mediation analysis found that propionate mediates sex‐specific associations between SCFAs and cerebrospinal fluid biomarkers. SCFA levels are associated with slower cognitive decline. DISCUSSION These results link SCFAs and propionate‐producing bacteria with AD. This may inform efforts to leverage diet and specific bacteria to boost SCFA production and potentially ameliorate AD progression. Highlights Fecal SCFAs link to lower amyloid burden and microglial activation, notably in females. SCFA‐producing gut microbes have reduced abundance in amyloid‐positive participants. Fecal propionate mediates relationships between gut microbes and amyloid status. SCFAs are associated with slower plasma pTau 217 accumulation in females. SCFAs are associated with slower cognitive decline.

  PublisherOA PDFDOI

• Gut microbiota strain richness is species specific and affects engraftment

  Nature · 2024-11-27 · 52 citations

  articleOpen access
  PublisherOA PDFDOI

• Relationships Between Microbiome‐derived Short Chain Fatty Acids and Alzheimer’s Disease Pathology Biomarkers: A Human Cohort Study

  Alzheimer s & Dementia · 2024-12-01 · 3 citations

  articleOpen access

  Abstract Background Alzheimer’s Disease (AD) is the most common form of dementia, and therapies that effectively halt disease progression are lacking. Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are abundant gut bacterial metabolites produced via fermentation of dietary fibers and resistant starch. There is growing evidence that SCFAs may affect key neuropathological processes underlying AD, but their role is not well established. Understanding how gut microbial metabolites relate to AD biomarkers may help elucidate gut microbiome contributions to disease progression. Method Here, we measured levels of several SCFAs in fecal samples collected from 124 participants in the Microbiome Alzheimer’s Research Study (MARS) using headspace gas chromatography. Participants were enrolled in the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention, which track preclinical disease progression in cohorts enriched for AD risk. We performed multiple regressions to identify associations between SCFA abundance and diagnosis, amyloid positivity, age, sex, BMI, APOE status, and cerebrospinal fluid (CSF) biomarkers of AD. Result Acetate, propionate, and butyrate had significantly lower concentrations in females and in amyloid‐positive participants within both the full cohort and only cognitively unimpaired participants, suggesting that these associations may be preclinical. SCFAs had associations with several CSF biomarkers before FDR multiple comparison correction, within the full cohort and preclinically. Hexanoate and butyrate had negative associations with Aβ42/40; hexanoate had a positive association with sTREM2, a marker of microglial activation, and NfL, a marker of neurodegeneration. Isobutyrate had a negative association with YKL‐40, a marker of astrocytes. Preclinically, isobutyrate and isovalerate had a negative association with NfL, and acetate had a positive association with GFAP, a marker of CNS astrocytes. An exploratory analysis found a SCFA‐by‐sex interaction on CSF biomarkers: in males, isobutyrate, isovalerate, and hexanoate had a negative association with YKL‐40, while in females, valerate and hexanoate had a negative association with Aβ42/40. Metagenomic analysis investigated associations with SCFA production‐related genes. Conclusion The three most abundant SCFAs (acetate, propionate, and butyrate) had lower concentrations in females and in amyloid‐positive participants in a human cohort enriched for AD risk. Fecal SCFAs have associations with AD CSF biomarkers in the same cohort.

  PublisherOA PDFDOI

Recent grants

• NIH Grant F32GM013995

  NIH · $63k

Frequent coauthors

• Federico E. Rey

  University of Wisconsin–Madison

  35 shared

• Gary P. Roberts

  American Dental Association

  35 shared

• Hwan Youn

  California State University, Fresno

  19 shared

• Kazuyuki Kasahara

  Duke-NUS Medical School

  12 shared

• Fredrik Bäckhed

  University of Gothenburg

  12 shared

• Ramnik J. Xavier

  Broad Institute

  12 shared

• Sanjay Asthana

  Geriatric Research Education and Clinical Center

  11 shared

• Marc V. Thorsteinsson

  United States Military Academy

  11 shared

Labs

• Kerby LabPI