Biology subjects

Walk, S.

Publications and source records attributed to Walk, S..

4 recordsLinked to original sources

bioRxiv2026

Interkingdom glycine conjugates of indole-3-carboxylates are Ah receptor ligands

Substituted indoles are conserved metabolites across all kingdoms of life and may function as a mediators of inter- and intra-species communication. Indole-3-carboxylates (indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA)) represent abundant tryptophan-derived AHR agonists in human serum, potentially influencing AHR-dependent physiology. LC-MS analysis of mouse serum, urine and cecal/fecal contents reveals that both IAA and IPA undergo host and microbial mediated glycine conjugation to facilitate urinary elimination. Notably, at physiologically detectable human serum concentrations (M), IAA-Glycine retains human AHR activation potential. Comparative in silico docking simulations corroborate IAA-Glycine as a direct ligand for the human AHR. Data suggest, in contrast to xenobiotic ligands, AHR activation by endogenous tryptophan metabolites is greater in humans than in mice. These results underscore the role of microbial and host-derived amino acid conjugation in generating bioactive metabolites. Thus, positioning interkingdom auxin chemistry within human physiology and revealing an unexpected link between plants, microbes, and humans.

biochemistry↗

bioRxiv2023

Persistence-colonization trade-off and niche differentiation enable the coexistence of E. coli phylogroups

Despite extensive literature on the pathogenicity and virulence of the opportunistic pathogen Escherichia coli, much less is known about its ecological and evolutionary dynamics as a commensal in healthy hosts. Based on two detailed longitudinal datasets on the gut microbiota of healthy adult individuals followed over months to years in France and in the USA, we identified a robust trade-off between the ability to establish in a new host (colonization) and the ability to remain in the host (residence). Major E. coli lineages (phylogroups) exhibited similar fitness but a diversity of strategies, from strong colonizers residing for a few days in the gut, to poor colonizers residing for years. Strains with the largest number of extra-intestinal virulence associated genes and highest pathogenicity resided for longest in hosts. Moreover, the residence time of a strain was reduced more strongly when it competed with other strains of the same phylogroup than of different phylogroups, suggesting niche differentiation between them. To investigate the consequences of the trade-off and niche differentiation for coexistence between strains, we developed a discrete-state Markov model describing the dynamics of E. coli in a population of hosts. We found that the trade-off and niche differentiation acted together as equalizing and stabilizing mechanisms enabling the coexistence of phylogroups over extended periods of time. Our model predicted that a reduction in transmission (e.g. better hygiene) would not alter the balance between phylogroups, while disturbance of the microbiome (e.g. antibiotics) would hinder residents strains such as those of the extra-intestinal pathogenic phylogroup B2.3.

evolutionary biology↗

bioRxiv2022

The gut microbiome has sexually dimorphic effects on bone tissue energy metabolism and multiscale bone quality in C57BL/6J mice

The gut microbiome impacts bone mass, implying a disruption to bone homeostasis, yet significant uncertainty remains regarding the impacts of the gut microbiome on remodeling bone cells. The gut microbiome is thought to be essential for normal biomineralization, but the specific consequences of the absent gut microbiome on tissue mineralization and multiscale bone quality are not determined. We hypothesized that bone homeostasis and tissue-scale metabolism, tissue mineralization, and whole-bone biomechanics are altered in germ-free (GF) C57BL/6J mice. Further, because many characteristics of the gut microbiome are sexually dimorphic, we hypothesized that the gut microbiome would show important sex differences with regards to its impact on bone quality. Differences between GF and conventional mouse bone extended from bone tissue metabolism to whole bone biomechanics. Cortical bone tissue from male mice had a greater signature of amino acid metabolism whereas female cells had a greater signature of lipid metabolism. These sex differences were also present in GF mice and were indeed even more stark. GF increased cortical femur bone formation for both sexes and decreased bone resorption and osteoclast density only in females. GF similarly increased cortical femur tissue mineralization and altered collagen structure for both sexes but led to greater gains in distal femur trabecular microarchitecture for males. Whole femur strength was similarly increased with GF for both sexes, but males had a greater increase in modulus. GF did not impact fracture toughness for either sex. The altered bone quality with GF is multifactorial and is likely contributed to by differences in tissue-scale composition as well as lower cortical porosity. Together, these data demonstrate that the gut microbiome influences bone cells and multiscale bone quality, but that the specific relationships that underlie these effects to bone are different for females and males.

microbiology↗

bioRxiv2017

Bacterial Colonization Stimulates A Complex Physiological Response In The Immature Human Intestinal Epithelium

The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is diZcult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.

developmental biology↗