Biology subjects

Samuel, B. S.

Publications and source records attributed to Samuel, B. S..

6 recordsLinked to original sources

bioRxiv2026

Neuroendocrine arylhydrocarbon receptor regulates gut microbiome of C. elegans via redox tone

The gut microbiome profoundly influences host health, with disrupted microbial communities implicated in inflammatory, metabolic, and neurological diseases. The aryl hydrocarbon receptor (AHR) shapes intestinal immunity and microbial composition, yet the mechanisms by which AHR mediates selective microbiome assembly remain poorly understood. Whether distant organ systems such as the nervous system actively participate in microbial community regulation is unexplored. Here we show that Caenorhabditis elegans neuronal AHR-1 orchestrates selective gut microbiome assembly through a neuroendocrine cascade that calibrates intestinal redox tone. Using a defined natural microbiome community, we demonstrate that ahr-1 loss triggers specific microbiome changes, as Enterobacterales and Pseudomonadales bloom up to 24-fold while Sphingobacteriales decline. Adult-specific AHR-1 depletion recapitulates this dysbiosis, separating the role of AHR-1 in neurodevelopment from its regulation of the microbiome. Neuronal AHR-1 regulates expression of the neuropeptide FLP-8 in oxygen-sensing URX neurons, which in turn signals to the intestine to modulate intestinal redox tone. Elevated intestinal redox tone in ahr-1 mutants favors growth of oxidative stress-tolerant Enterobacterales and Pseudomonadales, which also exhibit functional and genomic enrichment for stress resistance and AHR ligand biosynthesis pathways. This establishes a precise feedback circuit whereby AHR-1 senses bacterial metabolic output to regulate colonization by ligand-producing taxa. AHR-1 signaling regulates redox tone through downstream regulation of glutathione S-transferase GST-4 and alpha-arrestin ARRD-11. Intestinal gst-4 knockdowns had the greatest impact on restoring redox tone and microbiome compositional control in the gut. These findings reveal an evolutionarily ancient molecular circuit where AHR serves as a precision metabolic sensor that coordinates whole organismal physiology to maintain host-microbiome homeostasis.

genetics↗

bioRxiv2023

Metabolic model predictions enable targeted microbiome manipulation through precision prebiotics

1.The microbiome is increasingly receiving attention as an important modulator of host health and disease. However, while numerous mechanisms through which the microbiome influences its host have been identified, there is still a lack of approaches that allow to specifically modulate the abundance of individual microbes or microbial functions of interest. Moreover, current approaches for microbiome manipulation such as fecal transfers often entail a non-specific transfer of entire microbial communities with potentially unwanted side effects. To overcome this limitation, we here propose the concept of precision prebiotics that specifically modulate the abundance of a microbiome member species of interest. In a first step, we show that defining precision prebiotics by compounds that are only taken up by the target species but no other species in a community is usually not possible due to overlapping metabolic niches. Subsequently, we present a metabolic modeling network framework that allows us to define precision prebiotics for a two-member C. elegans microbiome model community comprising the immune-protective Pseudomonas lurida MYb11 and the persistent colonizer Ochrobactrum vermis MYb71. Thus, we predicted compounds that specifically boost the abundance of the host-beneficial MYb11, four of which were experimentally validated in vitro (L-serine, L-threonine, D-mannitol, and {gamma}-aminobutyric acid). L-serine was further assessed in vivo, leading to an increase in MYb11 abundance also in the worm host. Overall, our findings demonstrate that constraint-based metabolic modeling is an effective tool for the design of precision prebiotics as an important cornerstone for future microbiome-targeted therapies.

systems biology↗

bioRxiv2021

Modulation of sensory perception by hydrogen peroxide enables Caenorhabditis elegans to find a niche that provides both food and protection from hydrogen peroxide

Hydrogen peroxide (H2O2) is the most common chemical threat that organisms face. Here, we show that H2O2 alters the bacterial food preference of Caenorhabditis elegans, enabling the nematodes to find a safe environment with food. H2O2 induces the nematodes to leave food patches of laboratory and microbiome bacteria when those bacterial communities have insufficient H2O2-degrading capacity. The nematodes behavior is directed by H2O2-sensing neurons that promote escape from H2O2 and by bacteria-sensing neurons that promote attraction to bacteria. However, the input for H2O2-sensing neurons is removed by bacterial H2O2-degrading enzymes and the bacteria-sensing neurons perception of bacteria is prevented by H2O2. The resulting cross-attenuation provides a general mechanism that ensures the nematodes behavior is faithful to the lethal threat of hydrogen peroxide, increasing the nematodes chances of finding a niche that provides both food and protection from hydrogen peroxide.

neuroscience↗

bioRxiv2021

Natural genetic variation drives microbiome selection in the Caenorhabditis elegans gut

Host genetic landscapes can shape microbiome assembly in the animal gut by contributing to the establishment of distinct physiological environments. However, the genetic determinants contributing to the stability and variation of these microbiome types remain largely undefined. Here, we use the free-living nematode Caenorhabditis elegans to identify natural genetic variation among wild strains of C. elegans strains that drives assembly of distinct microbiomes. To achieve this, we first established a diverse model microbiome that represents the phylogenetic and functional diversity naturally found in the C. elegans microbiome. Using this community, we show that C. elegans utilizes immune, xenobiotic and metabolic signaling pathways to favor the assembly of different microbiome types. Variations in these pathways were associated with the enrichment for specific commensals, including the Alphaproteobacteria Ochrobactrum. Using RNAi and mutant strains, we showed that host selection for Ochrobactrum is mediated specifically by host insulin signaling pathways. Ochrobactrum recruitment is blunted in the absence of daf-2/IGFR and requires the insulin signaling transcription factors daf-16/FOXO and pqm-1/SALL2. Further, the ability of C. elegans to enrich for Ochrobactrum is correlated positively with host outcomes, as animals that develop faster are larger and have higher gut Ochrobactrum colonization as adults. These results highlight a new role for the highly conserved insulin signaling pathways in the regulation of microbiome composition in C. elegans.

microbiology↗

bioRxiv2020

Population scale nucleic acid delivery to Caenorhabditis elegans via electroporation

The free-living nematode C.elegans remains one of the most robust and flexible genetic systems for inter-rogating the complexities of animal biology. Targeted genetic manipulations, such as RNA interference (RNAi), CRISPR/Cas9- or array-based transgenesis, all depend on initial delivery of nucleic acids. Delivery of dsRNA by feeding can be effective, but expression in E. coli is not conducive to experiments intended to remain sterile or with defined microbial communities. Soaking-based delivery requires prolonged exposure of animals to high material concentrations without a food source and is of limited throughput. Last, microinjection of individual animals can precisely deliver materials to animals germlines, but is limited by the need to target and inject each animal one-by-one. Thus, we sought to address some of these challenges in nucleic acid delivery by developing a population-scale delivery method. We demonstrate efficient electroporation-mediated delivery of dsRNA throughout the worm and effective RNAi-based silencing, including in the germline. Finally, we show that guide RNA delivered by electroporation can be utilized by transgenic Cas9 expressing worms for population-scale genetic targeting. Together, these methods expand the scale and scope of genetic methodologies that can be applied to the C.elegans system.

genetics↗

bioRxiv2020

CeMbio - The C. elegans microbiome resource

The study of microbiomes by sequencing has revealed a plethora of correlations between microbial community composition and various life-history characteristics of the corresponding host species. However, inferring causation from correlation is often hampered by the sheer compositional complexity of microbiomes, even in simple organisms. Synthetic communities offer an effective approach to infer cause-effect relationships in host-microbiome systems. Yet the available communities suffer from several drawbacks, such as artificial (thus non-natural) choice of microbes, microbe-host mismatch (e.g. human microbes in gnotobiotic mice), or hosts lacking genetic tractability. Here we introduce CeMbio, a simplified natural Caenorhabditis elegans microbiota derived from our previous meta-analysis of the natural microbiome of this nematode. The CeMbio resource is amenable to all strengths of the C. elegans model system, strains included are readily culturable, they all colonize the worm gut individually, and comprise a robust community that distinctly affects nematode life-history. Several tools have additionally been developed for the CeMbio strains, including diagnostic PCR primers, completely sequenced genomes, and metabolic network models. With CeMbio, we provide a versatile resource and toolbox for the in-depth dissection of naturally relevant host-microbiome interactions in C. elegans. Dataset accession numbersWhole genome sequencing data (PRJNA624308); microbiome sequencing [PRJEB37101 and PRJEB37035]; data supplement on the GSA Figshare Portal.

microbiology↗