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International Journal of Molecular... Nov 2022The colon has a very large surface area that is covered by a dense mucus layer. The biomass in the colon includes 500-1000 bacterial species at concentrations of ~10... (Review)
Review
The colon has a very large surface area that is covered by a dense mucus layer. The biomass in the colon includes 500-1000 bacterial species at concentrations of ~10 colony-forming units per gram of feces. The intestinal epithelial cells and the commensal bacteria in the colon have a symbiotic relationship that results in nutritional support for the epithelial cells by the bacteria and maintenance of the optimal commensal bacterial population by colonic host defenses. Bacteria can form biofilms in the colon, but the exact frequency is uncertain because routine methods to undertake colonoscopy (i.e., bowel preparation) may dislodge these biofilms. Bacteria in biofilms represent a complex community that includes living and dead bacteria and an extracellular matrix composed of polysaccharides, proteins, DNA, and exogenous debris in the colon. The formation of biofilms occurs in benign colonic diseases, such as inflammatory bowel disease and irritable bowel syndrome. The development of a biofilm might serve as a marker for ongoing colonic inflammation. Alternatively, the development of biofilms could contribute to the pathogenesis of these disorders by providing sanctuaries for pathogenic bacteria and reducing the commensal bacterial population. Therapeutic approaches to patients with benign colonic diseases could include the elimination of biofilms and restoration of normal commensal bacteria populations. However, these studies will be extremely difficult unless investigators can develop noninvasive methods for measuring and identifying biofilms. These methods that might include the measurement of quorum sensing molecules, measurement of bile acids, and identification of bacteria uniquely associated with biofilms in the colon.
Topics: Humans; Biofilms; Quorum Sensing; Colonic Diseases; Bacteria
PubMed: 36430737
DOI: 10.3390/ijms232214259 -
Gut Microbes 2022The immune system in the large intestine is separated from commensal microbes and comparatively rare enteric pathogens by a monolayer of diverse epithelial cells... (Review)
Review
The immune system in the large intestine is separated from commensal microbes and comparatively rare enteric pathogens by a monolayer of diverse epithelial cells overlaid with a compact and adherent inner mucus layer and a looser outer mucus layer. Microorganisms, collectively referred to as the mucus-associated (MA) microbiota, physically inhabit this mucus barrier, resulting in a dynamic and incessant dialog to maintain both spatial segregation and immune tolerance. Recent major findings reveal novel features of the crosstalk between the immune system and mucus-associated bacteria in health and disease, as well as disease-related peripheral immune signatures indicative of host responses to these organisms. In this brief review, we integrate these novel observations into our overall understanding of host-microbiota mutualism at the colonic mucosal border and speculate on the significance of this emerging knowledge for our understanding of the prevention, development, and progression of chronic intestinal inflammation.
Topics: Colon; Gastrointestinal Microbiome; Humans; Immune System; Inflammation; Intestinal Mucosa; Mucus; Symbiosis
PubMed: 35239459
DOI: 10.1080/19490976.2022.2041342 -
IEEE Transactions on Medical Imaging Jul 2020Point-of-care medical diagnosis demands immediate feedback on tissue pathology. Confocal endomicroscopy can provide real-time in vivo images with histology-like...
Point-of-care medical diagnosis demands immediate feedback on tissue pathology. Confocal endomicroscopy can provide real-time in vivo images with histology-like features. The working channel in medical endoscopes are becoming smaller in dimension. Microsystems methods can produce tiny mechanical scanners. We demonstrate a flexible fiber instrument for in vivo imaging as an endoscope accessory. The optical path is folded on-axis to reduce length while allowing the beam to expand and achieve a numerical aperture of 0.41. A high-speed parametric resonance mirror produces large deflection angles > 13°, and is mounted on a 2 mm diameter chip designed with clamp structures for reduced space. A compact lens assembly provides diffraction-limited lateral and axial resolution of 1.5 and [Formula: see text], respectively. A working distance of [Formula: see text] and field-of-view of [Formula: see text] m are achieved. Miniature apparatus is fabricated to assemble and align the scanhead components. The optics and scanner are packaged in a distal tip with 2.4 mm diameter and 10 mm rigid length. These dimensions allow the endomicroscope to pass forward easily through the 2.8 mm diameter working channel in medical endoscopes commonly used in clinical practice. Fluorescence images are collected in vivo at 10 frames per second in the colon of genetically-engineered mice that spontaneously develop adenomas. A FITC-labeled peptide heterodimer is administered intravenously to provide specific contrast. Sub-cellular structures are visualized to distinguish pre-malignant from normal mucosa. These results demonstrate use of microsystems methods to produce an ultra-compact instrument with sufficiently small dimensions for broad use.
Topics: Animals; Colon; Mice
PubMed: 32012007
DOI: 10.1109/TMI.2020.2971476 -
Cureus Sep 2023The colon has a large surface area covered with a thick mucus coating. Colon's biomass consists of about 1,012 colony-forming units per gram of feces and 500-1,000... (Review)
Review
The colon has a large surface area covered with a thick mucus coating. Colon's biomass consists of about 1,012 colony-forming units per gram of feces and 500-1,000 distinct bacterial species. The term (IBD) indicates the collection of intestinal illnesses in which the digestive system (esophagus, large intestine, mouth, stomach, and small intestine) experiences persistent inflammation. IBD development is influenced by environmental (infections, stress, and nutrition) and genetic factors. The microbes present in gut microbiota help maintain intestinal homeostasis and support immune and epithelial cell growth, differentiation, as well as proliferation. It has been discovered that a variety of variables and microorganisms are crucial for the development of biofilms and mucosal colonization during IBD. An extracellular matrix formed by bacteria supports biofilm production in our digestive system and harms the host's immunological response. Irritable bowel syndrome (IBS) and IBD considerably affect human socioeconomic well-being and the standard of living. IBD is a serious public health issue, affecting millions of people across the globe. The gut microbiome may significantly influence IBS pathogenesis, even though few diagnostic and treatment options are available. As a result, current research focuses more on disrupting biofilm in IBD patients and stresses primarily on drugs that help improve the quality of life for human well-being. We evaluate studies on IBD and bacterial biofilm to add fresh insights into the existing state of knowledge of biofilm formation in IBD, incidence of IBD patients, molecular level of investigations, bacteria that are involved in the formation of biofilm, and present and down the line regimens and probiotics. Planning advanced ways to control and eradicate bacteria in biofilms should be the primary goal to add fresh insights into generating innovative diagnostic and alternative therapy options for IBD.
PubMed: 37868553
DOI: 10.7759/cureus.45510 -
Gastroenterology Apr 2021Patients with inflammatory bowel disease (IBD) demonstrate nutritional selenium deficiencies and are at greater risk of developing colon cancer. Previously, we...
BACKGROUND & AIMS
Patients with inflammatory bowel disease (IBD) demonstrate nutritional selenium deficiencies and are at greater risk of developing colon cancer. Previously, we determined that global reduction of the secreted antioxidant selenium-containing protein, selenoprotein P (SELENOP), substantially increased tumor development in an experimental colitis-associated cancer (CAC) model. We next sought to delineate tissue-specific contributions of SELENOP to intestinal inflammatory carcinogenesis and define clinical context.
METHODS
Selenop floxed mice crossed with Cre driver lines to delete Selenop from the liver, myeloid lineages, or intestinal epithelium were placed on an azoxymethane/dextran sodium sulfate experimental CAC protocol. SELENOP loss was assessed in human ulcerative colitis (UC) organoids, and expression was queried in human and adult UC samples.
RESULTS
Although large sources of SELENOP, both liver- and myeloid-specific Selenop deletion failed to modify azoxymethane/dextran sodium sulfate-mediated tumorigenesis. Instead, epithelial-specific deletion increased CAC tumorigenesis, likely due to elevated oxidative stress with a resulting increase in genomic instability and augmented tumor initiation. SELENOP was down-regulated in UC colon biopsies and levels were inversely correlated with endoscopic disease severity and tissue S100A8 (calprotectin) gene expression.
CONCLUSIONS
Although global selenium status is typically assessed by measuring liver-derived plasma SELENOP levels, our results indicate that the peripheral SELENOP pool is dispensable for CAC. Colonic epithelial SELENOP is the main contributor to local antioxidant capabilities. Thus, colonic SELENOP is the most informative means to assess selenium levels and activity in IBD patients and may serve as a novel biomarker for UC disease severity and identify patients most predisposed to CAC development.
Topics: Adolescent; Animals; Azoxymethane; Case-Control Studies; Cell Transformation, Neoplastic; Child; Child, Preschool; Colitis; Colitis, Ulcerative; Colitis-Associated Neoplasms; Colon; DNA Damage; Dextran Sulfate; Disease Models, Animal; Female; Genomic Instability; Humans; Intestinal Mucosa; Liver; Male; Mice, Knockout; Myeloid Cells; Oxidative Stress; Selenoprotein P; Mice
PubMed: 33388316
DOI: 10.1053/j.gastro.2020.12.059 -
BMC Cancer Oct 2023The existence of amino acid metabolic reprogramming in tumor cells is well established. However, the potential correlation between blood amino acids and the risk of...
BACKGROUND
The existence of amino acid metabolic reprogramming in tumor cells is well established. However, the potential correlation between blood amino acids and the risk of colon adenocarcinoma remains largely unexplored.
METHODS
We utilized Mendelian randomization (MR) analysis to examine the association between 20 amino acids in the blood and the risk of colon adenocarcinoma. Additionally, reverse MR analysis was employed to identify the presence of reverse causality. A two-step MR analysis was conducted to ascertain the potential mediating effect. Lastly, the alanine detection data from colon adenocarcinoma patients in our hospital were utilized to investigate the differences in alanine levels among healthy individuals and patients with colon cancer, as well as among patients with different stages and locations of colon cancer. Furthermore, a Kaplan-Meier curve was employed to examine the correlation between alanine and overall survival, followed by the implementation of COX univariate analysis.
RESULTS
The results of our study indicate that there is an inverse correlation between alanine and the risk of colon adenocarcinoma. Additionally, we found no significant evidence to support a causal relationship between colon adenocarcinoma and alanine. Furthermore, our analysis revealed that alanine aminotransferase (ALT) and blood glucose do not act as mediators in this causal pathway. Moreover, individuals diagnosed with colon adenocarcinoma exhibited a significant decrease in alanine levels, particularly in cases of stage IV colon adenocarcinoma with distant metastasis. Additionally, elevated alanine levels were associated with improved overall survival rates among colon adenocarcinoma patients.
CONCLUSIONS
The results of this study indicate that alanine exhibits protective characteristics against the onset of colon adenocarcinoma and may play a role in promoting a more favorable disease prognosis. Consequently, dietary interventions aimed at increasing alanine intake may serve as a potential strategy for the prevention and treatment of colon adenocarcinoma.
Topics: Humans; Adenocarcinoma; Amino Acids; Mendelian Randomization Analysis; Colonic Neoplasms; Alanine; Genome-Wide Association Study
PubMed: 37898769
DOI: 10.1186/s12885-023-11514-w -
Cell Reports. Medicine Sep 2023Research on gut microbiota has generally focused on fecal samples, representing luminal content of the large intestine. However, nutrient uptake is restricted to the... (Review)
Review
Research on gut microbiota has generally focused on fecal samples, representing luminal content of the large intestine. However, nutrient uptake is restricted to the small intestine. Abundant immune cell populations at this anatomical site combined with diminished mucus secretion and looser junctions (partly to allow for more efficient fluid and nutrient absorption) also results in intimate host-microbe interactions despite more rapid transit. It is thus crucial to dissect key differences in both ecology and physiology between small and large intestine to better leverage the immense potential of human gut microbiota imprinting, including probiotic engraftment at biological sensible niches. Here, we provide a detailed review unfolding how the physiological and anatomical differences between the small and large intestine affect gut microbiota composition, function, and plasticity. This information is key to understanding how gut microbiota manipulation, including probiotic administration, may strain-dependently transform host-microbe interactions at defined locations.
Topics: Humans; Colon; Intestine, Small; Biological Transport; Feces; Probiotics
PubMed: 37683651
DOI: 10.1016/j.xcrm.2023.101190 -
BMJ Open Gastroenterology Jul 2021Global survival studies have shown favourable development in colon and rectal cancers but few studies have considered extended periods or covered populations for which...
OBJECTIVES
Global survival studies have shown favourable development in colon and rectal cancers but few studies have considered extended periods or covered populations for which medical care is essentially free of charge.
DESIGN
We analysed colon and rectal cancer survival in Finland and Sweden over a 50-year period (1967-2016) using data from the Nordcan database. In addition to the standard 1-year and 5-year survival rates, we calculated the difference between these as a novel measure of how well survival was maintained between years 1 and 5.
RESULTS
Relative 1-year and 5-year survival rates have developed favourably without major shifts for men and women in both countries. For Finnish men, 1-year survival in colon cancer increased from 50% to 82%, and for rectal cancer from 62% to 85%. The Swedish survival was a few per cent unit better for 1-year survival but for 5-year survival the results were equal. Survival of female patients for both cancers was somewhat better than survival in men through 50 years. Overall the survival gains were higher in the early compared with the late follow-up periods, and were the smallest in the last 10 years. The difference between 1-year and 5-year survival in colon cancer was essentially unchanged over the 50-year period while in rectal cancer there was a large improvement.
CONCLUSIONS
The gradual positive development in survival suggests a contribution by many small improvements rather than single breakthroughs. The improvement in 5-year survival in colon cancer was almost entirely driven by improvement in 1-year survival while in rectal cancer the positive development extended to survival past year 1, probably due to successful curative treatments. The current challenges are to reinvigorate the apparently stalled positive development and to extend them to old patients. For colon cancer, survival gains need to be extended past year 1 of diagnosis.
Topics: Colon; Female; Finland; Humans; Male; Rectal Neoplasms; Registries; Sweden
PubMed: 34272211
DOI: 10.1136/bmjgast-2021-000644 -
Biochimica Et Biophysica Acta.... Jul 2021The human colon balances water and electrolyte absorption and secretion while also forming a barrier protecting the body from the entry of harmful components.... (Review)
Review
The human colon balances water and electrolyte absorption and secretion while also forming a barrier protecting the body from the entry of harmful components. Aquaporin-3 (AQP3) is a water, glycerol and HO transporting channel expressed in colonic epithelia. Although expression of colonic epithelial AQP3 is altered in several intestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, the regulation and specific roles of AQP3 remain to be fully defined. In this mini-review, we summarize the current understanding of the expression, regulation, and biological functions of AQP3 protein in colonic epithelia concerning intestinal absorption, secretion and barrier function.
Topics: Aquaporin 3; Colon; Epithelial Cells; Gene Expression Regulation; Humans; Hydrogen Peroxide; Inflammatory Bowel Diseases; Models, Biological; Water
PubMed: 33811845
DOI: 10.1016/j.bbamem.2021.183619 -
Mucosal Immunology May 2022Intestinal epithelial barrier function is compromised in inflammatory bowel disease and barrier dysfunction contributes to disease progression. Extracellular...
Intestinal epithelial barrier function is compromised in inflammatory bowel disease and barrier dysfunction contributes to disease progression. Extracellular nucleotides/nucleosides generated in gut inflammation may regulate barrier function through actions on diverse cell types. Enteric glia modulate extracellular purinergic signaling and exert pathophysiological effects on mucosal permeability. These glia may regulate inflammation with paracrine responses, theoretically mediated via adenosine 2B receptor (AR) signaling. As the cell-specific roles of ARs in models of colitis and barrier dysfunction are unclear, we studied glial ARs in acute dextran sodium sulfate (DSS) colitis. We performed and validated conditional ablation of glial ARs in Sox10;Adora2b mice. Overt intestinal disease activity indices in DSS-colitis were comparable between Sox10;Adora2b mice and littermate controls. However, ablating glial ARs protected against barrier dysfunction following acute DSS-colitis. These benefits were associated with the normalization of tight junction protein expression and localization including claudin-1, claudin-8, and occludin. Glial AR signaling increased levels of proinflammatory mediators in the colon and cell-intrinsic regulation of genes including Csf3, Cxcl1, Cxcl10, and Il6. Our studies show that glial AR signaling exacerbates immune responses during DSS-colitis and that this adenosinergic cell-specific mechanism contributes to persistent gut epithelial barrier dysfunction.
Topics: Adenosine; Animals; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Inflammation; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Neuroglia
PubMed: 35869148
DOI: 10.1038/s41385-022-00550-7