Biology subjects

Bae, M.

Publications and source records attributed to Bae, M..

16 recordsLinked to original sources

bioRxiv2026

Surfactant-Assisted Colorimetric Signal Enhancement in Paper-Based Glucose Sensing

Paper-based colorimetric sensors offer a low-cost and accessible platform for point-of-care (POC) analysis, but enzyme activity loss during coating and drying can weaken analytical signals and require high enzyme loadings or complex immobilization procedures. Although surfactants are widely used to improve wettability in paper-based assays, their potential contribution to colorimetric performance beyond these effects remains unclear. Here, we investigated surfactant-assisted colorimetric signal enhancement in a glucose assay implemented on a 96-puddle paper plate (96-PPP) and identified Tween 20 as the most effective surfactant. Its effect on detection performance became more pronounced as glucose oxidase (GOx) loading decreased; at 0.1 mg/mL GOx, Tween 20 lowered the limit of detection (LoD) from 0.113 to 0.034 mg/mL (approximately 3.3-fold) over a working range of 0-5 mg/mL, despite no statistically significant change in the measured contact angle at this loading. Tween 20 had no appreciable effect on the reaction in solution but preserved 95% of the apparent reaction rate constant after drying, compared with 11% without it, and atomic force microscopy (AFM) revealed a more dispersed dried enzyme morphology on mica. Tween 20-containing sensors also showed slower signal decay during repeated wetting-drying cycles and thermal stress, retained 77% (vs 26%) of the response at 400 mM NaCl, and exhibited within-PPP and between-batch coefficients of variation (CVs) below 10% (vs 12.3-19.5%), while maintaining glucose selectivity over potentially interfering molecules. These results indicate that Tween 20 enhances paper-based glucose sensing beyond wettability, in part by retaining enzyme cascade activity during drying, although the contributions of the individual enzymes and the underlying mechanism remain to be established.

bioengineering↗

bioRxiv2026

Pore-Resolved High-Throughput Quantification of Amyloid Aggregation and Amplification

Amyloid fibrils are implicated in a wide spectrum of neurodegenerative and systemic disorders, yet their biological consequences are governed not only by total fibril content but also by how fibrillar species are organized, clustered, and amplified within heterogeneous populations. Conventional thioflavin T (ThT)-based assays provide sensitive sample-level readouts of {beta}-sheet-rich material but offer limited access to the local population structure underlying amyloid aggregation and amplification. Here, we introduce the Amyloid Pore Quantification (APQ) chip, a pore-resolved geometric partitioning platform that converts heterogeneous amyloid assembly states into fluorescence intensity distributions across thousands of defined pore-level units. Using hen egg-white lysozyme as a model amyloid-forming protein, we combine length-controlled truncated amyloid nanofibrils with vacuum-assisted ThT infiltration to establish a reproducible pore fluorescence intensity reference. APQ provided quantitative concentration-dependent calibration across a 50-fold concentration range, enabling bulk-comparable quantification while preserving pore-level distribution information. Deviations from this reference resolved pH-dependent fibril clustering near the isoelectric point as pore-signal suppression and accessibility loss, captured pepsin-associated fibrillar amplification as a population-wide increase in pore intensity, and distinguished monomer- and oligomer-driven fibril processing through coupled amplification-aggregation fingerprints. When benchmarked against ensemble fluorescence measurements and AFM morphological analysis, APQ revealed assembly-state changes that were not fully represented by sample-level ThT intensity alone. These results establish APQ as a high-throughput, distribution-aware analytical framework for translating amyloid aggregation and amplification into quantitative pore-resolved fingerprints.

bioengineering↗

bioRxiv2026

Mechanochemically Programmed, Oligomer-Selective Amyloid Assembly via Axial Rotation

Amyloid oligomers have been widely implicated as primary cytotoxic intermediates; however, their selective and scalable production remains challenging due to rapid fibril amplification. Here, we demonstrated that sustained axial rotation enables programmable mechanochemical control over amyloid pathway selection without the use of chemical additives. Using a thermal axial rotator, native monomeric hen egg-white lysozyme was incubated at 60 {degrees}C under quantitatively tunable rotational speeds, imposing defined centrifugal forces and wall-associated shear that restructured the hydrodynamic boundary conditions. A discrete transition emerged near 600 RPM, separating the two distinct assembly regimes. Below this threshold, aggregation followed a fibril-amplifying pathway characterized by elevated {beta}-sheet content and elongated fibrillar morphologies. Above this threshold, fibrillar growth was strongly attenuated and oligomer-dominant assemblies predominated. Spectroscopic analyses and atomic force microscopy revealed that axial rotation redistributes the amyloid assembly states rather than simply suppressing aggregation. Functionally, the RPM-defined assemblies exhibited kinetically distinct seeding behaviors and induced divergent cytotoxic phenotypes in SH-SY5Y neuroblastoma cells. These findings establish axial rotation-mediated hydrodynamic boundary control as a scalable, chemical-free strategy for reprogramming amyloid assembly pathways and producing oligomer-rich assemblies with well-defined structural and functional properties.

bioengineering↗

bioRxiv2026

Comparative Analysis of Relative Ligand Binding Free Energy Simulation Methods: Amber-TI, GROMACS-NETI, OpenMM-FEP, and BLaDE-MSLD

Structure-based drug design has become increasingly important in the pharmaceutical industry for accelerating the discovery of effective drug candidates. In particular, ligand binding free energy serves as a critical metric for predicting drug efficacy during the key stages of hit discovery and lead optimization. Continuous progresses have been made in the prediction of ligand binding free energies, but direct comparisons of different methods using the same force field remain challenging due to their unique implementations into different simulation engines. In this study, we present a direct comparison of four popular methodologies (Amber-TI, GROMACS-NETI, OpenMM-FEP, and BLaDE-MSLD) for calculating relative binding free energies ({Delta}{Delta}Gbind) with the same Amber protein and ligand force fields using MolCube Alchemical Free Energy Simulator (MolCube-AFES), which provides an input generation workflow to support {Delta}{Delta}Gbind calculations of all four methods. We used 80 alchemical transformations (among the JACS benchmark set by Wang et al.) and two additional applications to compare the predicted {Delta}{Delta}Gbind from the four methods against experimental measurements. All four methods reproduced experimentally observed trends with most transformations within {+/-}2 kcal/mol from experiments and show broadly comparable accuracy with no statistically significant performance differences across the benchmark dataset. These results demonstrate that MolCube-AFES enables controlled, cross platform benchmarking and show that all four different alchemical free energy methods deliver statistically equivalent accuracy, with method selection guided by workflow requirements such as throughput, portability, and perturbation network design rather than expected differences in performances.

biophysics↗

bioRxiv2026

Activating Ras-MAPK pathway variants drive hippocampal clonal competition in human epilepsy

Mesial (a.k.a., medial) temporal lobe epilepsy (MTLE) is the most common focal epilepsy1,2 and, in drug-resistant cases, is treated by surgical removal of the anterior temporal lobe, which often shows neuronal loss and gliosis consistent with hippocampal sclerosis (HS)2. MTLE with HS has minimal contribution from germline genetic variation3, and is associated with prior precipitating insults such as prolonged childhood seizures and head trauma4-6. Somatic variants in Ras-MAPK pathway genes were recently reported in a few MTLE surgical specimens7,8, but their prevalence, clinical relevance, and underlying biological mechanisms remain unknown. Targeted duplex sequencing of hippocampal DNA from 462 surgical resections revealed significant enrichment of deleterious somatic variants in MTLE versus controls, with >40% of MTLE specimens harboring activating Ras-MAPK variants in PTPN11, NF1, BRAF, KRAS, and twelve genes not previously associated with focal epilepsy. Eight Ras-MAPK genes showed positive clonal selection in MTLE. Increased somatic variant burden predicted worse surgical outcome. Somatic Ras-MAPK variants at ultra-low (<0.5%) variant allele fractions were associated with older seizure onset and HS pathology, supporting a late prenatal or postnatal origin. Ras-MAPK variants in MTLE were enriched in cells derived from hippocampal progenitors--neurons, astrocytes, oligodendrocytes--in line with the known neuronal hyperexcitability and seizures induced by Ras-MAPK overactivation9,10; in contrast, Alzheimer disease hippocampi exhibited microglial enrichment of Ras-MAPK variants, consistent with prior reports11. Single-nucleus RNA sequencing showed increased expression of Ras-MAPK genes in neurons and upregulation of pathways mediating neurogenesis and neural development in MTLE. Functional validation of novel, recurrent PTPN11 variants confirmed gain-of-function, while cellular modeling in induced pluripotent stem cells demonstrated proliferative/survival advantages for mutant cells in mosaic culture. Overall, our data suggest that somatic Ras-MAPK variants and acquired risk factors may converge on clonal competition in the hippocampus to modulate epilepsy risk.

genetics↗

bioRxiv2025

Multi-platform framework for mapping somatic retrotransposition in human tissues

Mobile element insertions (MEI) shape the human genome in both germline and somatic tissues. While inherited MEIs are well characterized, mapping somatic MEIs (sMEI) in non-cancer tissues remains challenging due to their low allelic fraction and repetitive nature. We established an integrative framework for sMEI analysis leveraging modern sequencing technologies and analytical innovations. We first benchmarked sMEI detection and demonstrated advantages of long-read and MEI-targeted sequencing for ultra-low-frequency events using a mixture of well-established cell lines. We then showed that haplotype phasing and donor-specific assemblies refine sMEI detection, effectively distinguishing from germline and false signals in in-silico tumor-normal mixtures. We further developed a source-tracing strategy based on internal sequence variation, expanding the catalogue of active source elements beyond traditional transduction-based methods. Applying this framework to donor tissues, we identified 18 rare somatic L1 insertions, revealing structural and source diversity. Our work provides a foundational framework and biological insight into sMEIs.

genomics↗

bioRxiv2025

VEGFR2 blockade overcomes acquired KRAS G12D inhibitor resistance driven by PI3Kγ activation

KRAS G12D mutation is a key oncogenic driver in many solid tumors, including pancreatic, gastric, and colorectal cancers. While recent studies have characterized features associated with primary and acquired resistance to KRAS inhibitors, strategies to overcome such resistance, particularly in the context of gastrointestinal cancers, remain underexplored. Here, we have generated nine human gastrointestinal cancer models, including three patient-derived organoids (PDOs), with acquired resistance to the KRAS G12D-selective inhibitor MRTX1133. Using single-cell RNA sequencing analysis, we identified the enrichment of angiogenesis, hypoxia, and epithelial-to-mesenchymal transition (EMT) signatures in the resistant model compared to the parental PDO. Across all resistant models, VEGFA expression and VEGFR2 phosphorylation were uniformly elevated, which were driven by AKT activation and SP1 nuclear translocation. Mechanistic investigations uncovered increased PI3K{gamma} activity in MRTX1133-resistant models via complex formation of KRAS with p110{gamma} and p101. This leads to an autocrine VEGFA-VEGFR2 signaling loop formation and EMT induction. Therapeutically, the disruption of VEGFA-VEGFR2 signaling restored MRTX1133 sensitivity and inhibited EMT. Furthermore, cancer-endothelial paracrine signaling amplified angiogenesis, hypoxia, and EMT signatures in cancer cells and simultaneously promoted endothelial cell proliferation, reinforcing an adaptive feedback mechanism. In a mouse model of MRTX1133-resistant tumor xenograft, a combination of anti-VEGFR2 therapy and MRTX1133 more effectively reduced tumor growth, angiogenesis, and proliferation markers than monotherapy without significant body weight change. These findings establish VEGFA-VEGFR2 signaling by PI3K{gamma} activation as a key driver of acquired resistance to KRAS G12D inhibition and provide a rationale for combining VEGFA-VEGFR2 inhibition with KRAS blockade in KRAS-mutant cancers. HighlightO_LIVEGFA-VEGFR2 signaling activation is a common feature of MRTX1133 resistance in KRASG12D cancer cells C_LIO_LINuclear translocation of SP1 by AKT activation promotes VEGFA transcription in MRTX1133-resistant models C_LIO_LIInteraction of p110{gamma}-p101 with KRAS activates PI3K{gamma} in the resistant models C_LIO_LIVEGFA-VEGFR2 inhibition reverses MRTX1133 resistance in vitro and in vivo C_LI

cancer biology↗

bioRxiv2025

Systematic identification and characterization of regulators of aryl hydrocarbon receptor signaling

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.

genomics↗

bioRxiv2025

Scalable, high-throughput isolation of extracellular vesicles using electrokinetic-assisted mesh filtration

As extracellular vesicles (EVs) are increasingly recognized for their superior functions for therapeutics, the need for large-scale EV isolation technology is becoming more critical for clinical and industrial applications. Most existing EV isolation methods are optimized for small-scale laboratory samples, limiting their efficiency and scalability for large-scale production. Here, an electrokinetic-assisted filtration system (ExoFilter), which introduces charge interaction into physical mesh flow filtration, is proposed as a new candidate to address the challenges of scalable EV isolation. The hybrid filtration system demonstrates outstanding high-throughput EV isolation performance (a flux of [~]750 mL/min) using only a coarse physical filter, by electrokinetically arresting EVs flowing through the filter lattice. Furthermore, the recovery efficiency of ExoFilter, analyzed based on the ELISA results, was found to be approximately 98%, demonstrating the filters exceptional efficiency in EV isolation. Additionally, ExoFilter enables the rapid isolation of EVs from small samples as little as 200 {micro}L, facilitating quick and easy blood-based EV research. Furthermore, low-molecular-weight albumin from plasma samples was effectively removed. The high-throughput and high-efficiency characteristics of ExoFilter make it well-suited for scalable EV production, offering greater convenience for various clinical applications. HighlightsO_LIElectrokinetic-assisted mesh filtration (ExoFilter) enables scalable and rapid isolation of extracellular vesicles (EVs). C_LIO_LIA high throughput of [~]750 mL/min is demonstrated while maintaining high yield and purity. C_LIO_LIExoFilter effectively removes albumin contaminants from EVs through size-exclusive electrokinetic-assisted mesh filtration. C_LIO_LIEfficient EV isolation performance is achieved for human plasma, saliva, urine, and cell culture media. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/645682v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@7ac3d5org.highwire.dtl.DTLVardef@1ced638org.highwire.dtl.DTLVardef@521c63org.highwire.dtl.DTLVardef@c5bd49_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Recurrent patterns of widespread neuronal genomic damage shared by major neurodegenerative disorders

Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimers disease (AD) represent two major categories of neurodegenerative disorders--TDP-43 and tau proteinopathies--for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 469 neurons from C9ORF72 ALS, C9ORF72 FTD, AD, and control brains revealed increased somatic single nucleotide variants (sSNVs) and insertions/deletions (sIndels) in all three diseases. Mutational signature analysis identified a disease-associated sSNV signature consistent with oxidative damage and an sIndel process affecting 22% of ALS, 76% of FTD, and 61% of AD neurons--but only 2% of control neurons--resembling signature ID4, previously linked to topoisomerase 1 (TOP1)-mediated mutagenesis. Rapid Approach to DNA Adduct Recovery (RADAR) assays confirmed increased TOP1-DNA covalent complexes and duplex sequencing confirmed the increased sIndels and identified single-strand events as likely precursor lesions. TOP1-associated sIndel mutagenesis and genome instability thus represents a mechanism shared by both TDP-43 and tau neurodegeneration.

genomics↗

bioRxiv2025

Distinct Classes of Gut Bacterial Molybdenum-Dependent Enzymes Produce Urolithins

Urolithin A is an anti-aging and anti-inflammatory gut bacterial metabolite derived from ellagic acid (EA), a polyphenol abundant in berries and nuts. The conversion of EA to urolithin A involves multiple chemically challenging phenol dehydroxylation steps that produce urolithins with varying bioactivities. Despite their biological and chemical significance, the bacterial enzymes responsible for urolithin production remain unidentified. Here, we use differential gene expression analysis, anaerobic protein expression, and enzyme assays to identify members of two distinct molybdenum enzyme families (the DMSO reductase family and the xanthine oxidase family) capable of regioselective dehydroxylation and urolithin generation. These two enzyme families have distinct substrate requirements, suggesting they employ different catalytic mechanisms for phenol dehydroxylation. Multi-omics analysis of a human cohort uncovers decreased levels of urolithin A and genes encoding urolithin A-producing enzymes in patients with inflammatory bowel disease (IBD), implying reduced health effects of EA consumption in this setting. Together, this study elucidates the molecular basis of urolithin production, expands the known enzymatic repertoire of the human gut microbiome, and suggests a potential link between gut bacterial urolithin production and host inflammation. Significance statementThe human gut microbiome modulates the health effects of dietary compounds by modifying their chemical structures. For example, gut microbes extensively metabolize polyphenols, a group of diverse plant-derived compounds associated with positive health outcomes. Urolithin A, a gut bacterial metabolite derived from a polyphenol abundant in berries and nuts, exhibits potent anti-inflammatory activity. However, the gut bacterial enzymes involved in its production remain largely unknown. Here, we report urolithin-producing gut bacterial enzymes, including four phenol dehydroxylases from two distinct molybdenum-dependent enzyme families. Analyzing human gut microbiomes suggests a potential link between genes encoding these enzymes and host inflammation. Together, our findings fully map urolithin A production to enzymes, increasing our understanding of how the gut microbiome can alter the impacts of diet on human health.

biochemistry↗

bioRxiv2024

Changes in Electroencephalography signals in a juvenile female Fragile X Syndrome mouse model

BackgroundFragile X syndrome (FXS) is the leading monogenic cause of Autism. No broadly effective support option currently exists for FXS, and drug development has suffered many failures in clinical trials based on promising preclinical findings. Thus, effective translational biomarkers of treatment outcomes are needed. Recently, electroencephalography (EEG) has been proposed as a translational biomarker in FXS. Recent years have seen an exciting emergence of novel EEG signal analyses from FXS patients. However, there is a notable gap in corresponding analyses conducted on animal models of the disorder. Being X-linked, FXS is more prevalent in males than females, and there exist significant phenotype differences between males and females with FXS. Recent studies involving male FXS participants and rodent models have identified an increase in absolute gamma EEG power, while alpha power is found to be either decreased or unchanged. However, there is not enough research on female FXS patients or models. In addition, studying EEG activity in both young and adult FXS patients or rodent models is crucial for better understanding of the disorders effects on brain development. Therefore, using the well established fmr1 knockout (KO) mouse model of FXS, we aim to compare EEG signal between female wild-type (WT) and female model mice at both juvenile and adult ages. MethodsFrontal-parietal differential EEG was recorded using a stand-alone Open-Source Electrophysiology Recording system for Rodents (OSERR). EEG activity was recorded in three different conditions: a) in the subjects home cage, and in the arenas for b) light -dark test and c) open field test. Absolute and relative EEG power as well as peak alpha frequency, theta-beta ratio, phase-amplitude and amplitude-amplitude coupling, and EEG signal complexity were computed for each condition. ResultsIn our study, we found absolute alpha, beta, gamma and total EEG power is increased in the female model compared to WT controls at the juvenile and adult ages. Alongside, relative theta power is decreased in the model. Additionally, phase-amplitude and amplitude-amplitude coupling is altered in the model. Furthermore, peak alpha frequency is increase, and theta-beta ratio is decreased in the model. Lastly, no change in EEG signal complexity is found. Discussion and ConclusionConsistent with most findings from FXS patients and rodent models, our results demonstrated an increase in gamma power in fmr1KO female mice, reinforcing gamma power as a robust and reliable EEG phenotype across FXS models. Additionally, theta-gamma cross frequency amplitude coupling is inversely coupled in female FXS model, which is similar to what has been reported in FXS patients. Overall, our findings reveal that not all EEG biomarkers observed in FXS patients are replicated in the female FXS model. For example, peak alpha frequency, theta-beta ratio, and brain signal complexity showed discrepancies between the mouse models and FXS patients. Additionally, when compared to previously reported EEG changes in male FXS mouse models, our results highlight the presence of a potential sex-based difference in EEG phenotypes at both juvenile and adult stages of fmr1 KO mouse models. Together, our study indicates that certain EEG parameters may be more translatable between rodent models and FXS patients than others and underscore the importance of considering sex and developmental stage as a critical factor when using EEG as a biomarker in FXS research.

neuroscience↗

bioRxiv2021

Targeted degradation of the oncogenic phosphatase SHP2

SHP2 is a protein tyrosine phosphatase that plays a critical role in the full activation of the Ras/MAPK pathway upon stimulation of receptor tyrosine kinases (RTKs), which are frequently amplified or mutationally activated in human cancer. In addition, activating mutations in SHP2 result in developmental disorders and hematologic malignancies. Several allosteric inhibitors have been developed for SHP2 and are currently in clinical trials. Here, we report the development and evaluation of a SHP2 PROTAC created by conjugating RMC-4550 with pomalidomide using a PEG linker. This molecule is highly selective for SHP2, induces degradation of SHP2 in leukemic cells at sub-micromolar concentration, inhibits MAPK signaling, and suppresses cancer cell growth. SHP2 PROTACs serve as an alternative strategy for targeting ERK-dependent cancers and are useful tools alongside allosteric inhibitors for dissecting the mechanisms by which SHP2 exerts its oncogenic activity.

biochemistry↗

bioRxiv2021

A Bacterial Bile Acid Metabolite Modulates Treg Activity through the Nuclear Hormone Receptor NR4A1

Bile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4+ T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (Treg cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. We also show that the nuclear hormone receptor NR4A1 is required for the effect of isoalloLCA on Treg cells. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans.

immunology↗

bioRxiv2020

Bacterially produced small molecules stimulate diatom growth

Diatoms are photosynthetic microalgae that fix a significant fraction of the worlds carbon. Because of their photosynthetic efficiency and high-lipid content, diatoms are priority candidates for biofuel production. Here, we report that sporulating Bacillus thuringiensis when in co-culture with a marine diatom Phaeodactylum tricornutum significantly increases the diatom cell count. Bioassay-guided purification led to the identification of two diketopiperazines (DKPs) that both stimulate P. tricornutum growth and increase its lipid content. RNA-seq analysis revealed upregulation of a small set of P. tricornutum genes involved in iron starvation response and nutrient recycling when DKP was added to the diatom culture. This work demonstrates that two DKPs produced by a bacterium could positively impact P. tricornutum growth and lipid content, offering new approaches to enhance P. tricornutum-based biofuel production. As increasing numbers of DKPs are isolated from marine microbes, the work gives potential clues to bacterially produced growth factors for marine microalgae. One sentence summaryTwo diketopiperazines (DKPs) produced by sporulating bacterium Bacillus thuringiensis stimulate diatom P. tricornutum growth and increase diatom lipid content.

plant biology↗

bioRxiv2020

Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways

The intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EECs). EECs can communicate nutritional information to the nervous system, but similar mechanisms for microbial information are unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda specifically activates EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increases intestinal motility in an EEC-dependent manner. Microbial, pharmacological, or optogenetic activation of Trpa1+EECs directly stimulates vagal sensory ganglia and activates cholinergic enteric neurons through 5-HT. We identified a subset of indole derivatives of tryptophan catabolism produced by E. tarda and other gut microbes that potently activates zebrafish EEC Trpa1 signaling and also directly stimulates human and mouse Trpa1 and intestinal 5-HT secretion. These results establish a molecular pathway by which EECs regulate enteric and vagal neuronal pathways in response to specific microbial signals.

physiology↗