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Cellular and Molecular Gastroenterology... 2022Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon...
BACKGROUND & AIMS
Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon from 3 human beings.
METHODS
A total of 12,590 single epithelial cells from 3 independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and their capacity for response to extrinsic signals along the gut axis across different human beings.
RESULTS
Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4) cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the potential for variegated responses.
CONCLUSIONS
Our study identifies novel lineage marker genes, covers regional differences, shows important differences between mouse and human gut epithelium, and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves likely functional differences across anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.
Topics: Animals; Colon; Epithelium; Humans; Intestinal Mucosa; Intestine, Small; Mice; Transcriptome
PubMed: 35176508
DOI: 10.1016/j.jcmgh.2022.02.007 -
Immunity Aug 2020Paneth cells are the primary source of C-type lysozyme, a β-1,4-N-acetylmuramoylhydrolase that enzymatically processes bacterial cell walls. Paneth cells are normally...
Paneth cells are the primary source of C-type lysozyme, a β-1,4-N-acetylmuramoylhydrolase that enzymatically processes bacterial cell walls. Paneth cells are normally present in human cecum and ascending colon, but are rarely found in descending colon and rectum; Paneth cell metaplasia in this region and aberrant lysozyme production are hallmarks of inflammatory bowel disease (IBD) pathology. Here, we examined the impact of aberrant lysozyme production in colonic inflammation. Targeted disruption of Paneth cell lysozyme (Lyz1) protected mice from experimental colitis. Lyz1-deficiency diminished intestinal immune responses to bacterial molecular patterns and resulted in the expansion of lysozyme-sensitive mucolytic bacteria, including Ruminococcus gnavus, a Crohn's disease-associated pathobiont. Ectopic lysozyme production in colonic epithelium suppressed lysozyme-sensitive bacteria and exacerbated colitis. Transfer of R. gnavus into Lyz1 hosts elicited a type 2 immune response, causing epithelial reprograming and enhanced anti-colitogenic capacity. In contrast, in lysozyme-intact hosts, processed R. gnavus drove pro-inflammatory responses. Thus, Paneth cell lysozyme balances intestinal anti- and pro-inflammatory responses, with implications for IBD.
Topics: Animals; Clostridiales; Colitis, Ulcerative; Crohn Disease; Female; Gastrointestinal Microbiome; Goblet Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Muramidase; Paneth Cells; STAT6 Transcription Factor
PubMed: 32814028
DOI: 10.1016/j.immuni.2020.07.010 -
Case Reports in Gastroenterology 2022Colonic intramural hematoma is a rare condition and its endoscopic and radiological findings remain poorly described. An 82-year-old woman was hospitalized with a...
Colonic intramural hematoma is a rare condition and its endoscopic and radiological findings remain poorly described. An 82-year-old woman was hospitalized with a diagnosis of acute cerebral infarction. She immediately received anticoagulant therapy with argatroban for 1 week. With the appearance 4 days later of hematochezia, she was found to have severe anemia. Following insertion of the colonoscope, a large submucosal hematoma was shown to be present in the descending colon, with the mucosa shown to be necrotic and the residual mucosa around the hematoma shown to be yellowish. Computed tomography revealed a hyperdense mass in the descending colon. Laparoscopic colectomy was performed for the lesion diagnosed as intramural hematoma. Pathologically, it was a hematoma located in the subserosal layer involving full-thickness hemorrhage. To our knowledge, this report represents a valuable addition to the literature describing a case of colonic intramural hematoma whose diagnosis was effectively established by the combined use of CS and CT.
PubMed: 35814795
DOI: 10.1159/000524793 -
Microbiology Spectrum Jun 2022Nonalcoholic fatty liver disease (NAFLD) is a prevalent and progressive disease spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis...
Nonalcoholic fatty liver disease (NAFLD) is a prevalent and progressive disease spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), yet there is no effective treatment and efficient noninvasive diagnostic method for NASH. The present study investigated the longitudinal alternations of gut microbiota in the Western diet (WD) induced murine NAFLD model using 16S rRNA sequencing. Evident steatosis and inflammation were detected in the liver at the 8th and 12th week, while prompted hepatic oxidative injury and fibrosis were found at the 16th week. In this progressive process, impaired bile acid (BA) metabolism plays a vital part. Long-term WD intervention alters microbial richness and composition in the intestine, shaping characteristic microbial feature correspondence to each NAFLD stage. Descending abundances of and were found in NAFLD progression, while inflammation-related microbes , , and were verified to identify borderline NASH at 8th and 12th week, and BA-associated taxa , , , and were recognized as special symbols reflecting the state of oxidative damage and fibrosis in NASH at 16th week. Further, feces and colon abundances of were verified to be depleted in the process of borderline NASH progressed to NASH, and exhibited substantial correlations with NAFLD indexes ALT, AST, TC, and TBA. These characteristic taxa were effective to identify NAFLD and NASH, and microbiota-derived predictive models for NAFLD and NASH exhibited great potential (AUC 0.983 and 0.784). These findings demonstrate that a core set of gut microbiome especially BA-related taxa may be adopted as a noninvasive diagnostic tool for NAFLD and NASH. This study concentrates on longitudinal alternations of gut microbiota in NAFLD progression and discovers the interrelationships between them. These findings may uncover the role of gut microbiota in NAFLD progression and identify novel noninvasive diagnostic tools for NAFLD based on microbial biomarkers.
Topics: Animals; Fibrosis; Gastrointestinal Microbiome; Inflammation; Liver; Mice; Non-alcoholic Fatty Liver Disease; RNA, Ribosomal, 16S
PubMed: 35647690
DOI: 10.1128/spectrum.00047-22 -
Case Reports in Gastroenterology 2020Ischaemic colitis (IC) is the most frequent form of ischaemia of the digestive tract. Due to the worldwide increasing use of medications, there is a growing interest in...
Ischaemic colitis (IC) is the most frequent form of ischaemia of the digestive tract. Due to the worldwide increasing use of medications, there is a growing interest in drug-induced IC. This study reports a rare case of IC directly due to amoxicillin-clavulanate intake. The objective of the study was to describe the evolution of this novel manifestation. An 18-year-old man, non-smoker, with an insignificant medical history, presented with diarrhoea and cramping abdominal pain that started the day following the end of a 10-day amoxicillin-clavulanate course for recent upper respiratory tract infection. Stool cultures including toxin testing were negative. Colonoscopy documented an erosive-ulcerative colitis of the sigmoid and the descending colon. Histological examination of the colon biopsies revealed an IC with focal pseudomembranous areas in the descending-sigmoid colon. Thrombophilia screening tests were negative. The patient was discharged from the hospital without symptoms, and another colonoscopy was performed 3 weeks after the previous one, which documented normal endoscopic and histological findings. Amoxicillin-clavulanate IC is a very rare condition and should be suspected once infectious diseases, vascular/haemodynamic causes and a prothrombotic/hypercoagulable state have been excluded. Immediate discontinuation of the antibiotic leads to rapid disease remission.
PubMed: 32508555
DOI: 10.1159/000507014