George Birchenough

ORCID: 0000-0003-2283-2353
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About
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Research Areas
  • Gut microbiota and health
  • Helicobacter pylori-related gastroenterology studies
  • Probiotics and Fermented Foods
  • Escherichia coli research studies
  • Infant Nutrition and Health
  • Glycosylation and Glycoproteins Research
  • Immune Response and Inflammation
  • Mycobacterium research and diagnosis
  • Neonatal and Maternal Infections
  • Barrier Structure and Function Studies
  • Gastrointestinal motility and disorders
  • Aquaculture disease management and microbiota
  • Polysaccharides Composition and Applications
  • Enterobacteriaceae and Cronobacter Research
  • Platelet Disorders and Treatments
  • Pediatric Hepatobiliary Diseases and Treatments
  • Cystic Fibrosis Research Advances
  • Lipid Membrane Structure and Behavior
  • Viral gastroenteritis research and epidemiology
  • Blood properties and coagulation
  • Effects of Radiation Exposure
  • Cholangiocarcinoma and Gallbladder Cancer Studies
  • Invertebrate Immune Response Mechanisms
  • Proteoglycans and glycosaminoglycans research
  • IL-33, ST2, and ILC Pathways

University of Gothenburg
2016-2025

Wallenberg Wood Science Center
2025

Institute for Biomedicine
2025

University of Manchester
2021

University College London
2013

London School of Hygiene & Tropical Medicine
2011

Medway School of Pharmacy
2010

Mounting the intestinal barricades Gut microbiota are important for health and well-being, but they need to be kept under control prevented from doing any harm. Birchenough et al. investigated microbial molecules that trigger protective mucus secretion a class of goblet cells in colon. Once detected, an alarm signal is transmitted these via innate immune mediators inflammasome components adjacent cells, generating more repelling invaders. Subsequently, sentinel expelled epithelium their...

10.1126/science.aaf7419 article EN Science 2016-06-24

Objective The colonic inner mucus layer protects us from pathogens and commensal-induced inflammation, has been shown to be defective in active UC. aim of this study was determine the underlying compositional alterations, their molecular background potential contribution UC pathogenesis. Design In single-centre case–control study, sigmoid colon biopsies were obtained patients with ongoing inflammation (n=36) or remission (n=28), 47 without disease. Mucus samples collected ex vivo, protein...

10.1136/gutjnl-2018-317571 article EN cc-by-nc Gut 2019-03-26

Goblet cell diversity An adult human has a gut surface area averaging 30 square meters that is bombarded daily by xenobiotics and microorganisms. Mucus synthesized goblet cells supplies protective barrier coating. Nyström et al. discovered are not all the same along length of gut; rather, they form different functional populations depending on location. Small-intestine mucus laced with antimicrobial peptides permeable to small molecules; downstream, thicker generated excludes bacteria...

10.1126/science.abb1590 article EN Science 2021-04-15

The distal colon functions as a bioreactor and harbors an enormous amount of bacteria in mutualistic relationship with the host. microbiota have to be kept at safe distance prevent inflammation, something that is achieved by dense inner mucus layer lines epithelial cells. large polymeric nets made up heavily O-glycosylated MUC2 mucin forms this physical barrier. Proteomic analyses identified lectin-like protein ZG16 (zymogen granulae 16) abundant component. To elucidate function ZG16, we...

10.1073/pnas.1611400113 article EN Proceedings of the National Academy of Sciences 2016-11-14

The inner mucus layer (IML) is a critical barrier that protects the colonic epithelium from luminal threats and inflammatory bowel disease. Innate immune signaling thought to regulate IML formation via goblet cell Nlrp6 inflammasome activity controls secretion of structural component Muc2. We report isolated cells express components several inflammasomes; however, analysis properties in multiple inflammasome-deficient mice, including littermate-controlled Nlrp6−/−, detect functional all...

10.1084/jem.20190679 article EN cc-by-nc-sa The Journal of Experimental Medicine 2019-08-16

Many epithelial surfaces of the body are covered with protective mucus, and disrupted mucus homeostasis is coupled to diseases such as ulcerative colitis, helminth infection, cystic fibrosis, chronic obstructive lung disease. However, little known how a balanced system maintained. By investigating involvement proteases in colonic dynamics we identified metalloprotease activity be key contributor expansion. The effect was mediated by calcium-activated chloride channel regulator 1 (CLCA1)...

10.1016/j.ebiom.2018.05.031 article EN cc-by-nc-nd EBioMedicine 2018-06-07

Abstract The colonic mucus layer is organized as a two-layered system providing physical barrier against pathogens and simultaneously harboring the commensal flora. factors contributing to organization of this gel network are not well understood. In study, impact transglutaminase activity on architecture was analyzed. Here, we show that TGM3 major transglutaminase-isoform expressed synthesized in colon. Furthermore, intrinsic extracellular secreted demonstrated vitro ex vivo. Absence...

10.1038/s41467-021-27743-1 article EN cc-by Nature Communications 2022-01-11

Intestinal mucus barriers normally prevent microbial infections but are sensitive to diet-dependent changes in the luminal environment. Here we demonstrate that mice fed a Western-style diet (WSD) suffer regiospecific failure of barrier small intestinal jejunum caused by diet-induced aggregation. Mucus disruption due either WSD exposure or chromosomal Muc2 deletion results collapse commensal jejunal microbiota, which turn sensitizes atypical colonization enteric pathogen Citrobacter...

10.1016/j.celrep.2023.112084 article EN cc-by Cell Reports 2023-02-01

It has long been acknowledged that dietary fibres are important to maintain a healthy gut. Over the past decade, several studies have shown loss of complex polysaccharides from Western diet resulted in alterations our colonic microbiota. The concurrent increase incidence inflammatory bowel disease world driven us explore potential mechanistic link between diet, microbiota and host defence systems normally prevent inflammation. Using mice fed low fibre Western-style robust live tissue...

10.1080/19490976.2018.1513765 article EN Gut Microbes 2018-09-25

The colon epithelium is a primary point of interaction with the microbiome and regenerated by few rapidly cycling colonic stem cells (CSCs). CSC self-renewal proliferation are regulated growth factors presence bacteria. However, molecular link connecting diverse inputs that maintain homeostasis remains largely unknown. We report mediated redox-dependent activation epidermal factor receptor (EGFR) signaling via NADPH oxidase 1 (NOX1). NOX1 expression specific restricted to proliferative CSCs....

10.1016/j.celrep.2021.108949 article EN cc-by-nc-nd Cell Reports 2021-04-01

The increased prevalence of Clostridium difficile infection (CDI) has coincided with enhanced transmissibility and severity disease, which is often linked to two distinct clonal lineages designated PCR-ribotype 027 017 responsible for CDI outbreaks in the USA, Europe Asia. We assessed sporulation susceptibility three PCR-ribotypes; 012, four classes disinfectants; chlorine releasing agents (CRAs), peroxygens, quaternary ammonium compounds (QAC) biguanides. PCR-ribotype, showed highest...

10.1371/journal.pone.0025754 article EN cc-by PLoS ONE 2011-10-25

The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from host epithelium. Defects in have been linked to metabolic diseases, but previous studies predominantly investigated function during high-caloric/low-fiber dietary interventions, thus making it difficult separate effects mediated directly through diet quality potential obesity-dependent effects. As such, we decided examine mouse models with disease distinguish these factors. Here show that,...

10.1074/jbc.ra120.015771 article EN cc-by Journal of Biological Chemistry 2020-09-09

Two-day-old (P2), but not 9-day-old (P9), rat pups are susceptible to systemic infection following gastrointestinal colonization by Escherichia coli K1. Age dependency reflects the capacity of colonizing K1 translocate from (GI) tract blood. A complex GI microbiota developed P2, showed little variation over P2 P9, and did prevent stable colonization. Substantial developmental expression was observed including upregulation genes encoding components small intestinal (α-defensins Defa24...

10.1128/iai.00268-13 article EN Infection and Immunity 2013-06-25

The strong age dependency of neonatal systemic infection with Escherichia coli K1 can be replicated in the rat. Gastrointestinal (GI) colonization two-day-old (P2) rats leads to invasion blood within 48 h initiation colonization; pups become progressively less susceptible over P2-P9 period. We show that, animals colonized at P2 but not P9, E. bacteria gain access enterocyte surface mid-region small intestine and translocate through epithelial cell monolayer by an intracellular pathway...

10.1038/s41598-017-00123-w article EN cc-by Scientific Reports 2017-02-28

BackgroundRadiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet underlying pathophysiology still undefined. Most notably, although pelvic an acute intestinal inflammation there no consensus on whether late-phase contains inflammatory component or not. To address this knowledge gap, we examined potential presence a mucosal biopsies from irradiated survivors.MethodsWe...

10.1016/j.ebiom.2023.104691 article EN cc-by-nc-nd EBioMedicine 2023-07-21

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogenic Escherichia coli (UPEC) strains that can be found in patient intestines. Seeding of the urinary from this intestinal reservoir likely contributes to UTI recurrence (rUTI) rates. Thus, understanding factors promote UPEC colonization is critical importance designing therapeutics reduce rUTI incidence. Although E. high abundance large intestine mucus, little known about how it able maintain residence...

10.1126/sciadv.adp7066 article EN cc-by-nc Science Advances 2025-01-31

Regulated host–microbe interactions are a critical aspect of lifelong health. Colonic goblet cells protect from microorganisms via the generation mucus barrier structure. Bacteria-sensing sentinel provide secondary protection by orchestrating secretion when microbes breach barrier. Mucus deficiencies in germ-free mice implicate role for microbiota programming generation, but its natural ontogeny remains undefined. We now investigate and cell development relation to postnatal colonization....

10.1084/jem.20241591 article EN cc-by The Journal of Experimental Medicine 2025-05-05

Many neurotropic strains of Escherichia coli cause potentially lethal bacteraemia and meningitis in newborn infants by virtue their capacity to elaborate the protective polysialic acid (polySia) K1 capsule. Recombinant capsule depolymerase, endosialidase E (endoE), selectively removes polySia from bacterial surface; when administered intraperitoneally infected neonatal rats, enzyme interrupts transit E. gut brain via blood circulation prevents death systemic infection. We now show that...

10.1099/mic.0.036145-0 article EN Microbiology 2010-04-16

The secreted, goblet cell-derived protein Clca1 (chloride channel regulator, calcium-activated-1) has been linked to diseases with mucus overproduction, including asthma and cystic fibrosis. In the intestine is found in an abundance expression pattern similar Muc2, major structural component. We hypothesized that required for synthesis, structure or barrier function of intestinal therefore compared wild type Clca1-deficient mice under naive at various time points DSS (dextran sodium...

10.1371/journal.pone.0131991 article EN cc-by PLoS ONE 2015-07-10
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