Biology subjects

Matheis, F.

Publications and source records attributed to Matheis, F..

6 recordsLinked to original sources

bioRxiv2025

Sugar ABC transporter repertoires predict ecological dynamics in gut microbiome communities

The gut microbiome plays a central role in human health, but modern diets and lifestyles alter its composition. The microbial genomic traits that drive these ecological shifts, particularly in response to dietary sugars, remain poorly characterized. Here, we integrate a large dataset of longitudinal human diet-microbiome records and comparative genomics of human and murine gut isolates with in vitro and in vivo experiments to identify sugar ABC (ATP-binding cassette) transporters as key predictors of bacterial fitness and microbial community responses to dietary sugars. Strains encoding these transporters exhibit enhanced growth and consistently outcompete others in both monocultures and complex consortia across contexts. In gnotobiotic mice, dietary sugar supplementation selectively increases the expansion of sugar ABC transporter-positive bacteria, including the model gut pathobiont Escherichia coli. Systematic deletion of sugar transporter genes in E. coli revealed that a specific sugar ABC transporter gene was required to invade a model gut consortium, highlighting its importance in microbial competition. Together, these findings establish sugar ABC transporters as genomic predictors of microbial community dynamics in response to dietary sugars.

microbiology↗

bioRxiv2024

Sugar-rich foods exacerbate antibiotic-induced microbiome injury

Intestinal microbiota composition is implicated in several diseases; understanding the factors that influence it are key to elucidating host-commensal interactions and to designing microbiome-targeted therapies. We quantified how diet influences microbiome dynamics in hospitalized patients. We recorded 9,419 meals consumed by 173 patients undergoing hematopoietic cell transplantation and profiled the microbiome in 1,009 longitudinally collected stool samples from 158 of them. Caloric intake was correlated with fecal microbiota diversity. Bayesian inference revealed associations between intake of sweets or sugars during antibiotic exposure with microbiome disruption, as assessed by low diversity or expansion of the pathobiont Enterococcus. We validated this observation experimentally, finding that sucrose exacerbated antibiotic-induced Enterococcus expansion in mice. Taken together, our results suggest that avoiding sugar-rich foods during antibiotic treatment may reduce microbiome injury. One Sentence SummaryAnalyses of hematopoietic cell transplant patients and of mice uncover links between foods and microbiome disruption.

microbiology↗

bioRxiv2021

Enteric pathogens induce tissue tolerance and prevent neuronal loss from subsequent infections

The enteric nervous system (ENS) controls several intestinal functions including motility and nutrient handling, which can be disrupted by infection-induced neuropathies or neuronal cell death. We investigated possible tolerance mechanisms preventing neuronal loss and disruption in gut motility after pathogen exposure. We found that following enteric infections, muscularis macrophages (MMs) acquire a tissue-protective phenotype that prevents neuronal loss and dysmotility during subsequent challenge with unrelated pathogens. Bacteria-induced neuroprotection relied on activation of gut-projecting sympathetic neurons and signaling via {beta}2-adrenergic receptors ({beta}2AR) on MMs. In contrast, helminth-mediated neuroprotection was dependent on T cells and systemic production of interleukin (IL)-4 and -13 by eosinophils, which induced arginase-expressing MMs that prevented neuronal loss from an unrelated infection located in a different intestinal region. Collectively, these data suggest that distinct enteric pathogens trigger a state of disease- or tissue tolerance that preserves ENS number and functionality.

immunology↗

bioRxiv2021

c-MAF dependent perivascular macrophages regulate diet induced metabolic syndrome

Macrophages are an essential part of tissue development and physiology. Perivascular macrophages have been described in tissues and appear to play a role in development and disease processes, although it remains unclear what are the key features of these cells. Here, we identify a subpopulation of perivascular macrophages in several organs, characterized by their dependence on the transcription factor c-MAF, displaying non-conventional macrophage markers including LYVE1, Folate receptor 2 and CD38. Conditional deletion of c-MAF in macrophage lineages caused ablation of perivascular macrophages in the brain and altered muscularis macrophages program in the intestine. In the white adipose tissue (WAT), c-MAF deficient perivascular macrophages displayed an altered gene expression profile, which was linked to an increased vascular branching into the tissue. Upon feeding on high fat diet (HFD), mice with c-MAF deficient macrophages showed improved metabolic parameters compared to wild-type mice, including less weight gain, greater glucose tolerance and reduced inflammatory cell profile in WAT. These results define c-MAF as a central regulator of perivascular macrophages cell identity and transcriptional program in vivo and reveal a novel role for this tissue resident macrophage population in the regulation of metabolic syndrome.

immunology↗

bioRxiv2020

Microbiota-modulated enteric neuron translational profiling uncovers a CART+ glucoregulatory subset

Microbial density and diversity increase towards the distal intestine, affecting tissue physiology, metabolism, and function of both immune and nervous systems. Intrinsic enteric-associated neurons (iEAN) continuously monitor and modulate intestinal functions, including nutrient absorption and motility. Through molecular, anatomic and functional approaches, we characterized the influence of the microbiota on iEAN. We found that iEAN are functionally adapted to the intestinal segment they occupy, with a stronger microbiota influence on distal intestine neurons. Chemogenetic characterization of microbiota-influenced iEAN identified a subset of viscerofugal CART+ neurons, enriched in the distal intestine, able to modulate feeding through insulin-glucose levels. Retro- and anterograde tracing revealed that CART+ viscerofugal neurons send axons to the gut sympathetic ganglion and are synaptically connected to the liver and pancreas. Our results demonstrate a region-specific adaptation of enteric neurons and indicate that specific iEAN subsets are capable of regulating host physiology independently from the central nervous system. One Sentence SummaryMicrobes impact regionally defined intrinsic enteric neuron translatomes, including a novel CART+ glucoregulatory viscerofugal population.

neuroscience↗

bioRxiv2019

Adrenergic signaling in muscularis macrophages limits neuronal death following enteric infection

Enteric-associated neurons (EANs) are closely associated with immune cells and continuously monitor and modulate homeostatic intestinal functions, including motility. Bidirectional interactions between immune and neuronal cells are altered during disease processes such as neurodegeneration or irritable bowel syndrome. We investigated how infection-induced inflammation affects intrinsic EANs and the role of intestinal muscularis macrophages (MMs) in this process. Using murine model of bacterial infection, we observed long-term gastrointestinal symptoms including reduced motility and subtype-specific neuronal loss. Neuronal-specific translational-profiling uncovered a caspase 11-dependent EAN cell-death mechanism induced by enteric infections. MMs responded to luminal infection by upregulating a neuroprotective program; gain- and loss-of-function experiments indicated that {beta}2-adrenergic receptor ({beta}2-AR) signaling in MMs mediates neuronal protection during infection via an arginase 1-polyamine axis. Our results identify a mechanism of neuronal cell death post-infection and point to a role for tissue-resident MMs in limiting neuronal damage.

immunology↗