SEARCH · PubMed Health

Results for “Intestine, Small”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Characterization of small intestinal neuroendocrine tumorlets.

Small intestine neuroendocrine tumors (SI-NETs) frequently present as multifocal primaries. We commonly observe microscopic lesions in the superficial layer of the small intestine of SI-NET patients. We aimed to define them as small intestinal neuroendocrine tumorlets (SINTs) and explore their clinical and biological significance. Twenty multifocal and twenty unifocal SI-NETs patients who received resection at a single institution were retrospectively reviewed. Four hundred and forty six archived pathological slides were examined for microscopic lesions located in the lamina propria, muscularis mucosa, and superficial submucosa. Clinicopathological associations and progression-free survival were analyzed. Previously published genomic data were re-analyzed. SINTs were identified in 50% of multifocal and 30% of unifocal SI-NET patients. Median SINT size was 95 μm, with a median distance of 2.2 mm from the nearest mass. Compared to the 'true unifocal' group (unifocal without SINT), the 'multifocal-spectrum' group (multifocal or unifocal with SINT) had higher BMI (median: 27.6 vs 22.8, P = 0.0060), higher rates of perineural invasion (OR: 5.5, P = 0.044), larger mesenteric mass (median: 2.6 vs 1.6 cm, P = 0.034), and more advanced pT stage (pT3 or pT4, OR: 7.2, P = 0.018). Genomic re-analysis suggested that 13% of cells in multifocal primary tumors could share clonal origins, possibly indicating clonal spread via SINTs. SINTs may serve as a new biomarker for multifocal spectrum with local aggressiveness. The actual frequency of multifocal SI-NET may be higher than currently recognized in clinical practice. Further studies are needed to validate their prognostic and biological significance.

Humans↗

PubMed2025

Single-cell RNA-seq of small-intestinal neuroendocrine tumors reveals the cell of origin and gene expression of early tumor development.

Patients with a hereditary form of small-intestinal neuroendocrine tumors (SI-NETs) present with multiple synchronous tumors and precursors at various stages. Using this germline trait, single-cell RNA sequencing is performed to define the cell-of-origin and gene-expression trajectory in early tumor development. A subset of CES1(+), LCN15(-) enterochromaffin (EC) cells, residing at +4 position and below in the crypts, distinct from EC cells migrating up the villi, emerges as the putative SI-NET origin. PRODH2 is identified as a key biomarker for precursor cells, revealing stage-specific gene expression linked to early tumor development. From precursor to fully developed tumors, notable changes include the up-regulation of UCHL1 and MBD3L2, as well as the significant down-regulation of cell-cycle inhibitory genes, CDKN1A, CDKN1C, and CDKN2B, which play roles in cell survival and tumorigenesis. The current study provides insight into SI-NET initiation and progression, offering potential advancements in diagnosis, prevention, and treatment.

Neuroendocrine Tumors↗

PubMed2026

[Effects and mechanisms of Jiawei Yigong San on the Th17/Treg balance in food allergy].

Objective To explore the effects and mechanisms of Jiawei Yigong San (JWYGS) on the T helper type 17 (Th17)/regulatory T (Treg) cell balance in food allergy (FA). Methods Active components, action targets of JWYGS, and FA-related targets, were screened via network pharmacology. Overlapping targets between JWYGS and FA were used to construct a protein-protein interaction (PPI) network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed to predict key signaling pathways. Molecular docking was conducted to validate the binding affinity between the main active components and the predicted targets. Mice were randomly divided into control group, model group, JWYGS low-dose, medium-dose, and high-dose groups, and dexamethasone (DXM) group. An ovalbumin (OVA)-induced FA model was established. During the OVA challenge period, mice received daily intragastric administration, after which allergy and diarrhea scores were assessed. Small intestinal pathology was evaluated by HE staining. Serum ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 6 (IL-6), IL-17, IL-2, and IL-10 were measured by ELISA. Small intestinal IL-6, IL-17, and IL-10 protein expression was detected by immunohistochemistry. Splenic Th17 and Treg cells were quantified by flow cytometry, and the Th17/Treg ratio was calculated. The mRNA expression of IL-6, retinoic acid receptor-related orphan receptor γt (RORγt), and forkhead box protein P3 (FOXP3) in the small intestine was detected by qPCR. Results Network pharmacology identified 235 active components of JWYGS and 136 common targets. GO and KEGG enrichment analyses highlighted cytokine response and Th17 differentiation. Molecular docking confirmed stable binding between core components and targets. Compared with the control group, the model group exhibited aggravated allergy and diarrhea scores, marked small intestinal inflammation and mucosal damage, elevated serum levels of OVA-sIgE, IL-6, IL-17 and IL-2, along with increased splenic Th17 cell frequency and Th17/Treg ratio. Intestinal IL-6 and IL-17 protein levels as well as IL-6 and RORγt mRNA expression were upregulated, whereas serum IL-10 levels were decreased, and intestinal expression of IL-10 protein and FOXP3 mRNA was downregulated. After JWYGS treatment, allergy and diarrhea scores were significantly reduced. Small intestinal inflammation and mucosal damage were alleviated. Serum levels of OVA-sIgE, IL-17, IL-6 and IL-2, Th17 cell frequency and the Th17/Treg ratio, intestinal IL-6 and IL-17 protein levels were decreased. IL-6 and RORγt mRNA expression was downregulated. Serum IL-10 levels were increased and intestinal expression of IL-10 protein and FOXP3 mRNA was upregulated. Moreover, the JWYGS high-dose group demonstrated comparable efficacy to the DXM group. Conclusion JWYGS can ameliorate symptoms and reverse the Th17/Treg imbalance in FA mice, potentially by inhibiting IL-6 transcription and regulating RORγt/FOXP3 expression.

Animals↗

PubMed2026

Toxoplasma gondii infection disrupts secondary bile acid transformation in feline gut microbiota.

UNLABELLED: Bile acid (BA) transformation relies on gut microbiota and is vulnerable to Toxoplasma gondii infection, yet feline microbial BA-transforming capacity upon toxoplasmosis remains unclear. Here, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. The results revealed that the feline gut microbiome harbored widespread genetic potential for BA transformation but lacked a complete 7α-dehydroxylation pathway due to the absence of the key gene baiE. The BA transformation-related genomes (2,045 in total) were predominantly from the phyla Bacillota_A and Actinomycetota, among which only 37 encoded baiB, all belonging to Bacillota_A. The distribution of BA transformation-related genes varied across intestinal regions: genes encoding 7α-HSDH were primarily enriched in the small intestine, whereas genes encoding 3α-HSDH, baiCD, and baiH were more abundant in the large intestine. Additionally, the abundance of genes encoding BSH and 3α-HSDH increased significantly in the small intestine on day 3 post-infection, accompanied by increases in the phylum Bacillota_C and genera such as Blautia_A, Enterococcus_E, and Ligilactobacillus. Serum metabolomics revealed a significant increase in cholesterol levels post-infection, supporting the impact of T. gondii infection on intestinal BA transformation. These findings illustrated that the feline gut microbiota played an important role in BA transformation and that T. gondii infection disrupted the microbial potential for secondary BA transformation. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis. IMPORTANCE: Bile acid (BA) transformation plays a critical role in host metabolism and immune regulation. Although studies on BA transformation are increasing, the capacity for BA transformation within the feline gut microbiota and the impact of Toxoplasma gondii infection on this capacity remain unclear. To bridge this gap, we constructed a catalog of 2,474 nonredundant feline gut microbial genomes and integrated serum metabolomic data to verify BA transformation alterations. Our findings revealed that the feline gut microbiome lacked a complete 7α-dehydroxylation pathway, and the specific functions involved in BA transformation may differ between the small and large intestines. Furthermore, integrated metagenomic and serum metabolomic analyses suggested that T. gondii infection disrupted BA transformation capacity in the small intestine. This study provided new insights into gut microbiota-associated metabolic perturbations during feline toxoplasmosis.

Toxoplasma gondii↗

PubMed2026

Gastrointestinal digestion governs insect protein hydrolysis and predicted bioactive peptide release: Species-dependent implications for functional food applications.

This study investigates the digestion of insect proteins and the release of predicted bioactive peptides during human gastrointestinal digestion. Using the Infogest in vitro model, mealworm, cricket, and black soldier fly larvae (BSFL) proteins were digested and analyzed through discovery proteomics and bioinformatics to identify predicted bioactive peptides. Sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) quantified insect proteins including predicted bioactive peptide precursor proteins, the precursors of predicted bioactive peptides. Results indicated that gastrointestinal digestion strongly influences peptide release, with the gastric phase exhibiting a richer predicted bioactive peptide profile than the small intestinal phase. Many predicted bioactive peptides were rapidly hydrolysed under small intestine conditions, which may lead to reduced stability or diminished activity in vivo, potentially explaining why certain peptides show strong bioactivity in vitro but limited effects in vivo. Additionally, predicted bioactive peptide release varied by insect species, influenced by genetic factors and peptide abundance. These findings highlight the importance of species selection and consideration of proteolytic digestion patterns in optimizing insect-derived bioactive peptides for functional foods and nutraceutical applications.

Animals↗

PubMed2026

Interkingdom remodeling of the intestinal bacteriome and virome during Toxoplasma gondii infection in rats.

Toxoplasma gondii infection is associated with intestinal microbiome disruption, but its effects on genome-resolved bacterial populations, the gut virome, and bacteriome-virome relationships remain poorly understood. Using previously generated shotgun metagenomic datasets from 36 intestinal samples collected from 18 Sprague-Dawley rats across control, acute, and chronic infection groups, we reconstructed 294 quality-filtered, non-redundant bacterial metagenome-assembled genomes (MAGs) and identified 899 medium-to-high-quality viral operational taxonomic units (vOTUs) from assembled metagenomic contigs. Infection was associated with reduced bacterial richness in the small intestine during both acute and chronic stages and lower Shannon diversity during chronic infection. In contrast, large-intestinal α-diversity remained stable despite significant compositional reorganization. Taxonomic changes included increased Lactobacillus intestinalis, Limosilactobacillus reuteri, and Prevotella sp900547005, together with decreased Rothia sp002492045 and Akkermansia muciniphila. Functional profiling revealed region- and stage-specific changes in predicted bacterial metabolic potential, including reduced energy-related pathways and carbohydrate-active enzyme abundance. The virome also showed significant compositional changes in both intestinal regions. Quimbyviridae and Podoviridae_crAss-like viruses decreased in the small intestine during chronic infection, while Quimbyviridae, Flandersviridae, and Podoviridae_crAss-like viruses showed stage-specific decreases in the large intestine. Predicted bacterial hosts were assigned to 48.39% of vOTUs, with Lachnospiraceae and Ruminococcaceae being the most frequently linked families. Trans-kingdom networks further revealed region-specific positive and negative abundance correlations between bacterial and viral taxa. These findings extend previous microbiota-metabolome observations by integrating genome-resolved bacteriome analysis with contig-based virome profiling, providing a foundation for future mechanistic studies of toxoplasmosis-associated microbiome remodeling.

Gut virome↗

PubMed2015

Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets.

The recognized diversity of innate lymphoid cells (ILCs) is rapidly expanding. Three ILC classes have emerged, ILC1, ILC2 and ILC3, with ILC1 and ILC3 including several subsets. The classification of some subsets is unclear, and it remains controversial whether natural killer (NK) cells and ILC1 cells are distinct cell types. To address these issues, we analyzed gene expression in ILCs and NK cells from mouse small intestine, spleen and liver, as part of the Immunological Genome Project. The results showed unique gene-expression patterns for some ILCs and overlapping patterns for ILC1 cells and NK cells, whereas other ILC subsets remained indistinguishable. We identified a transcriptional program shared by small intestine ILCs and a core ILC signature. We revealed and discuss transcripts that suggest previously unknown functions and developmental paths for ILCs.

Animals↗

PubMed2025

Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin.

Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. However, the role of the mesenchyme in epithelial conversion into a fetal-like regenerative state after damage is not known. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM) and identify asporin (Aspn), an ECM-bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. After damage, transient increase in Aspn expression by the pericryptal fibroblasts induces epithelial transforming growth factor β (TGF-β)-signaling via CD44 and promotes timely epithelial reprogramming. Temporal control of Aspn is lost in old mice, and after damage, the persistently high level of Aspn stagnates epithelium in the regenerative state. Increase in Wnt signaling can resolve the stagnated regenerative program of the old epithelium, promoting restoration of tissue function. In summary, we establish a platform for modeling epithelial injury responses ex vivo and show that the mesenchymal Aspn-producing niche modulates tissue repair by regulating epithelial fetal-like reprogramming.

Animals↗

PubMed2026

Do Multi-Omics Approaches Improve the Diagnosis of Microbial Overgrowth Syndromes?

PURPOSE OF REVIEW: This review investigates how advances in breath testing (BT), small bowel (SB) culture, metagenomics, metatranscriptomics, transcriptomics and proteomics are reshaping the definition and diagnosis of small intestinal bacterial overgrowth (SIBO). It also discusses whether SIBO should be redefined as part of a larger group of microbial overgrowth syndromes. RECENT FINDINGS: Recent studies identify distinct hydrogen-, methane-, and hydrogen sulfide-associated overgrowth phenotypes, termed SIBO, intestinal methanogen overgrowth (IMO), and intestinal sulfide overproduction (ISO). SB sampling shows that these conditions involve different microbial patterns and functional activity, symptoms, and host responses. Quantitative shotgun metagenomics provides greater taxonomic and functional resolution than culture, while metatranscriptomics reveals active microbial pathways. On top of that, host transcriptomics and proteomics contribute to the better understanding of the predominant microbial effects in host cellular mechanisms in each of the distinct small bowel overgrowth types. SIBO has been increasingly identified as a disorder of microbial ecology and function rather than bacterial quantity alone. Integrating BT with SB sampling and multi-omics approaches may improve classification, clarify symptom mechanisms, and support a more individualized treatment, although standardized methods and further clinical validation remain necessary.

Humans↗

PubMed2026

Effects of Acalypha australis L. Extract on Growth Performance, Antioxidant Capacity and Intestinal Microbial Composition in Weaned Piglets.

The objective of this study was to investigate the effects of Acalypha australis L. extract (ALE) on the growth performance and intestinal health in piglets. A total of 24 weaned piglets were randomly allocated to three groups: the control group (CON), which was fed a basal diet, and the ALE0.5 and ALE1.0 groups, which were fed the basal diet supplemented with 0.5 and 1.0 g/kg of ALE, respectively. The measured variables included growth performance, digestive enzyme activity, intestinal morphology, antioxidant capacity, and intestinal microbiota and metabolites. The results showed that, compared to the CON group, supplementation of 1.0 g/kg ALE in the diets of weaned piglets significantly increased the ratio of gain to feed from 15 to 21 days (p < 0.05), decreased the diarrhea rate from Days 15 to 21 and Days 0 to 21 (p < 0.05), and increased the activities of pancreatic α-amylase, lipase, trypsin, and chymotrypsin, as well as duodenal α-amylase, lipase, and trypsin, and jejunal maltase and sucrase (p < 0.05). Additionally, supplementation of 1.0 g/kg ALE in the diet significantly improved the intestinal morphology of the duodenum and jejunum, as well as the expression of intestinal barrier-related genes in the small intestine (p < 0.05). Moreover, it significantly increased serum glutathione peroxidase activity and jejunal and ileal superoxide dismutase activities (p < 0.05), and also significantly increased the colonic propionic acid concentration of piglets (p < 0.05). The ALE supplementation increased the abundance of the colonic marker bacteria Collinsella in the piglets and influenced pathways related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. ALE can serve as a potential natural feed additive to regulate the structure of intestinal microbiota and metabolic pathways, enhance antioxidant capacity, improve intestinal health, reduce diarrhea incidence, and ultimately promote the growth performance of piglets.

Acalypha australis L. extract↗

PubMed2026

In vivo CRISPRi screens reveal Escherichia coli functional adaptations in the mouse gut.

Escherichia coli exhibits remarkable genetic diversity that enables it to adapt to the intestinal environment. Here we establish an in vivo CRISPR interference platform that leverages bacterial gene fitness as a high-resolution functional reporter of E. coli adaptations within mice harbouring a defined minimal microbial community (OligoMM12). The screen revealed that diet profoundly shapes the metabolic landscape of E. coli and the essential gene profile identified cross-feeding interactions. Comparison between a laboratory strain (MG1655), a uropathogenic strain (CFT073) and an adherent-invasive E. coli (AIEC LF82) identified distinct genetic requirements for intestinal colonization, highlighting divergent motility, stress response and respiration strategies. In a host inflammatory environment, we found that AIEC LF82 preferably colonized the small intestine with a mobile genetic element, Gally prophage, playing an important role in modulating fitness. These findings provide a high-resolution genetic atlas of E. coli's functional adaptation and demonstrate the utility of functional genomics to probe the gut environment itself.

Journal Article↗

PubMed2026

Identification and functional characterization of a novel antiviral chicken interferon-υ.

Interferons are critical mediators of antiviral immunity in vertebrates. While type IV interferon (IFN-υ) has been identified in fish and amphibians, its existence and function in chickens remained unknown. Through systematic genomic screening, we identified and cloned a novel chicken interferon gene, designated ChIFN-υ. Phylogenetic analysis placed ChIFN-υ within a distinct clade alongside zebrafish and clawed frog IFN-υ, confirming its identity as a type IV interferon, with minimal homology to classical type I, II, or III IFNs. Expression profiling revealed constitutive ChIFN-υ expression in mucosal and immune tissues of healthy chickens, exhibiting a distinct developmental shift: highest in trachea and small intestine in 1-day-old chicks, shifting to spleen and lung in 4-week-old chickens. ChIFN-υ expression was strongly upregulated following H9N2 AIV infection. Functionally, recombinant ChIFN-υ protein activated the interferon-stimulated response element (ISRE) and Mx promoter in a dose-dependent manner and significantly inhibited the replication of both vesicular stomatitis virus (VSV) and H9N2 AIV in DF-1 cells. In vivo, early treatment with exogenous ChIFN-υ significantly reduced pulmonary and tracheal viral loads and decreased oropharyngeal and cloacal virus shedding in H9N2-infected chickens. In conclusion, this study identifies and functionally characterizes the type IV interferon in chickens, elucidating the evolutionary status, regulated expression, and antiviral efficacy of ChIFN-υ. These findings highlight its potential as a candidate for developing interferon-based therapies against avian viral diseases.

Animals↗

PubMed2026

Gastrointestinal involvement in Ehlers-Danlos syndrome classical-like type 2 associated with a novel AEBP1 splice-site variant.

Ehlers-Danlos syndrome classical-like type 2 (clEDS2) is a rare autosomal recessive connective tissue disorder caused by biallelic loss-of-function variants in the gene encoding adipocyte enhancer-binding protein 1 (AEBP1). While cutaneous and skeletal manifestations are commonly observed, gastrointestinal complications, including bowel rupture, have been reported only rarely, and their histopathological basis remains poorly characterized. Here, we report findings of molecular investigations, gastrointestinal histopathological evaluation, and long-term clinical follow-up in the 16th reported patient with AEBP1-related clEDS2, complicated by spontaneous bowel perforation. A homozygous AEBP1 splice-site variant (NM_001129.5:c.1401-2 A > G) was identified by a custom next-generation sequencing-based panel analysis for hereditary connective tissue disorders. Transcript-level analysis by reverse transcription-polymerase chain reaction and Sanger sequencing demonstrated complete skipping of exon 12, resulting in a frameshift and predicted loss of function. Clinically, the patient experienced postoperative perforation in the sigmoid colon shortly after rectal cancer surgery, followed nearly 20 years later by spontaneous small intestinal perforation. Histopathological examination of the affected colonic tissue demonstrated mildly widened intermuscular spaces without other overt structural abnormalities. Notably, repeated upper and lower gastrointestinal endoscopic procedures were performed during long-term oncological surveillance without procedure-related bowel perforation. This observation could offer an opportunity to learn about gastrointestinal involvement in AEBP1-related clEDS2 and suggests that its gastrointestinal manifestations may differ in clinical context from those typically associated with vascular Ehlers-Danlos syndrome, warranting further investigation as additional cases are accumulated.

Humans↗

PubMed2026

Short-Term Success, Long-Term Failure: Strain Turnover and Virulence Re-Emergence May Drive Relapse in Pouchitis.

BACKGROUND & AIMS: Pouchitis, de-novo small intestinal inflammation is the most common complication developing in patients with ulcerative colitis after total large bowel resection and ileal pouch-anal anastomosis (IPAA) reconstruction. While the first line treatment is antibiotics, the microbial properties underlying flare, remission, and relapse remain vague. We aimed to investigate how antibiotic treatment drives microbial shifts that underlie remission and contribute to relapse. METHODS: Patients after IPAA were prospectively recruited during clinical flare (active pouchitis defined by the pouchitis disease activity index) and received a two-week course of metronidazole with either ciprofloxacin or doxycycline. Longitudinal follow up was conducted during a year. Clinical data were recorded, and fecal samples were obtained during consequent flares, recovery, and relapses. Microbial gene repertoire, strains, and resistance to antibiotics were determined. Metagenomic sequencing was integrated with whole-genome sequencing of Escherichia coli isolates, providing strain-specific virulence and antibiotic resistance profiles. RESULTS: Patients (n=21) recruited provided 130 samples over one-year follow-up. Both antibiotic regimens induced rapid but transient clinical improvement, reflected by a decrease in fecal calprotectin (728 to 265 μg/g, p<.05), and a marked reduction in bacterial exotoxin genes (p<.05), yet both parameters rebounded by 6 weeks post-treatment. Antibiotic resistance gene abundance significantly increased during treatment (p<.05), without expansion of resistance gene diversity, indicating that pre-existing resistant strains increased. CONCLUSIONS: Antibiotic-induced remission in pouchitis likely results from a temporary suppression of exotoxin-producing bacteria, enabling resistant, low-virulence strains to transiently dominate; The fact that harmful strains quickly rebound after treatment cessation highlights the need for targeted approaches to achieve sustained microbial control.

Inflammatory bowel disease↗

PubMed2026

Motif-centered analyses reveal universal and tissue-specific mutagenic mechanisms operating in the human body.

Somatic mutations are inevitable in human genomes and can lead to cancer initiation and tumor progression. Although many mutagenic processes have been linked to cancer, their activities in normal tissues before malignant transformation remain poorly characterized. Here, we analyzed the mutation profiles of 10,625 normal samples across 25 tissues obtained from whole-genome and whole-exome sequencing datasets. We applied stringent statistical hypothesis for detecting enrichment and enrichment-adjusted Minimal Estimate of Mutation Load in trinucleotide motifs preferred by known mutagenic processes. We found several cancer-associated mutational motifs in cancer-free tissues. Samples enriched with C→T mutations in nCg motif associated with clock-like spontaneous meCpG deamination were detected across all tissues. We also identified a second clock-like motif, T→C substitutions in aTn motif associated with exposure to small epoxides and other SN2 electrophiles, in several tissues. Motifs associated with other environmental and chemical mutagens showed sporadic and tissue-specific mutagenesis. APOBEC-induced C→T and C→G mutations in tCw motif were enriched in bladder, lung, small intestine, liver, and breast with preference for APOBEC3A-like mutagenesis in most tissues. Together, our analyses elucidated several cancer-associated mutagenic processes in normal tissues and provided a robust analytical framework for quantifying mutagenic activities from somatic mutation catalogs.

Humans↗

PubMed2025

Genome-wide mapping of cAMP receptor protein binding in enteroaggregative Escherichia coli reveals targeting of virulence-associated genes.

Bacterial pathogens employ a diverse array of virulence factors to colonize and subsequently elicit disease in their host. These factors are often subject to extensive regulation at the transcriptional level to ensure that their expression is timely. Although many pathogens use bespoke transcription factors that primarily target virulence genes, global transcription factors also sometimes play a role in controlling these genes. Enteroaggregative Escherichia coli (EAEC) is a significant cause of watery and mucoid diarrhoea globally. The organism colonizes the small intestine before producing toxins that elicit disease, using a multitude of virulence factors that are encoded both chromosomally and on virulence plasmids. In this work, we have studied the cAMP receptor protein (CRP), a well-characterized bacterial global transcription factor, focusing on its role in the pathogenicity of the prototype EAEC strain 042. We show that, although most functional CRP binding sites on the chromosome are conserved between E. coli K-12 and 042, CRP has been co-opted to couple the expression of some virulence genes to the nutritional state of the cell. We report novel mechanisms for CRP-dependent regulation of genes whose products contribute to the maturation of a bacterial antibiotic, export of a polysaccharide capsule and production of a putative adhesin.

Escherichia coli↗

PubMed2025

Genome-wide mapping of cyclic AMP receptor protein binding in Enteroaggregative Escherichia coli reveals targeting of virulence-associated genes.

Bacterial pathogens use a wide array of virulence factors to colonise and subsequently elicit disease in their host. These factors are often subject to extensive regulation at the transcriptional level, to ensure that their expression is timely. Although many pathogens use bespoke transcription factors that primarily target virulence genes, global transcription factors also sometimes play a role in controlling these genes. Enteroaggregative Escherichia coli (EAEC) is a significant cause of watery and mucoid diarrhoea globally. The organism colonises the small intestine before producing toxins that elicit disease, using a multitude of virulence factors that are encoded both chromosomally and on virulence plasmids. In this work, we have studied the cAMP Receptor Protein (CRP), a well-characterised bacterial global transcription factor, focusing on its role in pathogenicity of the prototype EAEC strain 042. We show that, although most functional CRP binding sites on the chromosome are conserved between E. coli K-12 and 042, CRP has been co-opted to couple the expression of some virulence genes to the nutritional state of the cell. We report novel mechanisms for CRP-dependent regulation of genes, whose products contribute to adhesion, production of a bacterial antibiotic, and export of a polysaccharide capsule.

CRP↗

PubMed2026

Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.

Somatic mutations are inevitable in human genomes and can lead to tumorigenesis, yet baseline mutagenesis in non-cancerous normal cells remain poorly understood. Here, we analyzed the mutation profiles of 11,949 normal samples across 25 tissues obtained from whole-genome and whole-exome sequencing datasets. We applied stringent statistical hypothesis for detecting enrichment and enrichment-adjusted Minimal Estimate of Mutation Load (MEML) in trinucleotide motifs preferred by known mutagenic processes. We found several cancer-associated mutational motifs in cancer-free tissues. Samples enriched with C→T mutations in nCg motif associated with clock-like spontaneous meCpG deamination were detected across all tissues. We revealed another clock-like motif, T→C substitutions in aTn motif associated with exposure to small epoxides and other SN2 electrophiles, in several tissues. Donors with several non-cancerous diseases showed significantly higher, age-independent, and concordant accumulation of aTn and nCg motifs compared to healthy donors. Motifs associated with chemical exposures showed sporadic, tissue and disease-specific mutagenesis. APOBEC-induced C→T and C→G mutations in tCw motif were enriched in bladder, lung, small intestine, liver, and breast with preference for APOBEC3A-like mutagenesis in most. Together, our analyses elucidated several ongoing mutagenic processes in normal human tissues and provided a robust analytical framework for identifying mutagenic sources from somatic mutation catalogues.

Journal Article↗