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AME medical journal 7, 10 (2022). doi:10.21037/amj-21-25

Constipation is one of the most common gastrointestinal complaints. Although the causes of constipation are varied, dietary habits have a significant influence. Excessive fat intake is suggested as one of the main causes of constipation; however, the exact mechanism is unknown. To investigate whether a high-fat diet (HFD) causes constipation in mice and to clarify the underlying mechanism, focusing on the amount of colonic mucus. Six-week-old male C57BL/6 mice were randomly divided into two groups: mice fed with HFD and those with normal chow diet (NCD). Fecal weight, water content, total gastrointestinal transit time, and colon transit time were measured to determine whether the mice were constipated. The colonic mucus was evaluated by immunostaining and quantified by spectrometry. Malondialdehyde (MDA) was measured using the thiobarbituric acid (TBA) test as a marker for oxidative stress. Compared to the NCD group, the weight of feces was less in the HFD group. In the functional experiment, the total gastrointestinal transit time and colon transit time were longer in the HFD group. Furthermore, HFD significantly reduced the amount of colonic mucus. In addition, the reduction in colonic mucus caused by surfactant resulted in constipation in the NCD group. HFD causes constipation with delayed colon transit time possibly via the reduction in colonic mucus in mice.

Psychological disorders are associated with increased risk of severe inflammatory bowel disease (IBD) by causing gut microbiota dysbiosis and colonic mucosal barrier damage. However, the interaction between chronic restraint stress (CRS), gut microbiota composition, and colonic mucus remains unclear. We demonstrated that mice under CRS conditions exhibited alterations in microbiota composition, disruption of colonic mucus, and aggravation of colitis. In addition, the abundance of Akkermansia muciniphila was significantly decreased in mice under CRS and UC patients with depression, and positively associated with the expression of MUC2. After antibiotic treatment, the recipient mice colonized with CRS microbiota showed barrier defects and severe colitis. Administration of Akkermansia muciniphila was found to restore colonic mucus and modify the gut microbiota. We confirm that CRS-mediated gut microbiota dysbiosis results in colonic mucosal barrier damage and aggravation of colitis. Our results suggest that A. muciniphila is expected to be a potential probiotic to protect and treat colonic mucus that is involved in IBD with psychological disorders.

The colonic mucus layer is organized as a two-layered system providing a physical barrier against pathogens and simultaneously harboring the commensal flora. The factors contributing to the organization of this gel network are not well understood. In this study, the impact of transglutaminase activity on this architecture was analyzed. Here, we show that transglutaminase TGM3 is the major TGM isoform expressed and synthesized in the colon. Furthermore, intrinsic extracellular TGM activity in the secreted mucus was demonstrated in vitro and ex vivo. Absence of this acyl-transferase activity resulted in faster degradation of the major mucus component the MUC2 mucin and changed the biochemical properties of mucus. Finally, TGM3-deficient mice showed an early increased susceptibility to DSS-induced colitis. Thus, these observations suggest that natural isopeptide cross-linking by TGM3 is important for mucus homeostasis and protection of the colon from inflammation, a suggested pre-stage of colon carcinoma.

INTRODUCTION: An intricate balance with our intestinal microbes is pivotal to health. A key interface of host-microbial interactions occurs in the mucus covering the intestinal epithelial surface. In the colon, the mucus layer serves as a barrier inhibiting direct epithelial contact with the dense population of microbes. Defects in this system are a hallmark of colitis. The mucus layer is structurally dependent on the polymeric mucin MUC2, and it is synthesized by goblet cells (GCs), specialized secretory cells classically viewed as a homogenous cell type. Studies identifying divergent functional features in GC subpopulations, including differential mucus biosynthesis rate and responses to bacteria, suggests GC populations may in fact be heterogeneous. RATIONALE: In the present study, we characterized intestinal GC expression diversity, and defined how a specific GC subtype, localized in the intercrypt surface epithelium, functionally contributes to the formation of the mucus barrier. RESULTS: Using mCherry-MUC2 transgenic mice to sort and isolate GCs, we generated transcriptomic and proteomic profiles to characterize the GC expression landscape in both the small intestine and colon. Single cell transcriptomic analysis revealed several unique GC clusters in each tissue regions, which segregated into two separate trajectories. One trajectory had enriched expression of known GC-specific genes (e.g., Clca1, Fcgbp), and was designated as canonical GCs. Conversely, the other trajectory was enriched for expression of genes typically associated with enterocytes (e.g., Dmbt1, Gsdmc4), which we designated as non-canonical GCs. In the colon, the most differentiated GCs are the high mucus turnover cells localized to the surface epithelium between crypts and were thus designated as intercrypt GCs (icGCs). These cells had distinct expression profiles from crypt-resident GCs, thus we investigated their role in forming the mucus barrier. We exploited the lectin binding features of mucus to resolve the three-dimensional organization of mucus in live tissue explants. Results demonstrated that icGCs secreted distinct mucus that filled the spatial regions between mucus plumes secreted from crypt openings. The intercrypt mucus was impenetrable to bacteria-sized beads; however, it was more penetrable to smaller molecules compared to crypt plume mucus. Penetrable surface mucus may be important for absorption of ions, and other compounds, while denser mucus within the crypt compartment contributes to the shielding of the stem cell niche. Both mucus subtypes appear to be important for the overall protective function of mucus, as a barrier impenetrable to bacteria was formed by the mixed net-like organization of intercrypt and crypt plume mucus. A mouse model with dysfunctional icGCs lacking normal intercrypt mucus exhibited an inadequate mucus barrier and was more susceptible to both chemically-induced and spontaneous (age-dependent) colitis, thus arguing for the indispensable role of icGCs in maintaining a functional mucus barrier. Furthermore, biopsies from patients with ulcerative colitis, also in remission, exhibited increased GC shedding and reduced icGC numbers. These characteristics was associated with structural defects in the mucus barrier, including gaps in the intercrypt mucus that exposed areas of the surface epithelium. CONCLUSION: The current study identifies GCs as a heterogeneous population of cells with diverse functional features that indicate a dynamic cellular system. GCs at different locations along the crypt-surface axis contribute to a functional mucus barrier that protects the epithelium from microorganisms. The icGCs possess a unique role in mucus organization, where their malfunction is associated with colitis in both mice and humans.

Vanessa L. Hale studies the role of the microbiome in disease susceptibility in animal and human health. In this mSphere of Influence article, she reflects on how the papers “Evolution of mammals and their gut microbes” (R. E. Ley, M. Hamady, C. Lozupone, P. J. Turnbaugh, et al., Science 320:1647–1651, 2008, https://doi.org/10.1126/science.1155725) and “A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility” (M. S. Desai, A. M. Seekatz, N. M. Koropatkin, N. Kamada, et al., Cell 167:1339–1353.e21, 2016, https://doi.org/10.1016/j.cell.2016.10.043) have provided a foundation for studying drivers of gut microbial structure and change across host species in the context of evolution and disease risk.

Dopamine regulates gastrointestinal mucosal barrier. Mucus plays important roles in the protection of intestinal mucosa. Here, the regulatory effect of dopamine on rat colonic mucus secretion was investigated. RT-PCR, immunofluorescence, Periodic Acid-Schiff reagent assay, Alcian blue-Periodic Acid-Schiff staining, and enzyme-linked immunosorbent assay were used to observe the expression of dopamine receptor and the direct effect of dopamine on the colonic mucus. Mice injected intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) destroying enteric dopamine (DA) neurons, rats microinjected with 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra damaging central dopaminergic neurons, and dopamine D5receptor-downregulated transgenic mice were used to detect the effect of endogenous enteric dopamine or dopamine receptors on distal colonic mucus. Our results indicated that D5immunoreactivity was widely distributed on the colonic goblet cells. Dopamine dose-dependently increased rat distal colonic mucus secretion in vitro. D1-like receptor antagonist SCH23390 inhibited dopamine (1 μΜ)-induced distal colonic mucus secretion. D1-like receptor agonist SKF38393 promoted mucin 2 (MUC2) secretion and increased the intracellular cAMP level of colonic mucosa. D5receptor-downregulated transgenic mice showed a decreased colonic MUC2 content. MPTP-treated mice exhibited lower colonic dopamine content and decreased colonic mucus content. 6-OHDA rats had an increase in the dopamine content in colonic mucosa but decreases in the protein levels of D1and D5receptors and MUC2 content in the colonic mucosa. These findings reveal that dopamine is able to promote distal colonic mucus secretion through the D5receptor, which provides important evidence to better understand the possible role of dopamine in the colonic mucosal barrier.

The imbalance of gut microbiota, such as dysbiotic expansion of Enterobacteriaceae, is strongly associated with the progress of inflammatory bowel disease (IBD) via exacerbating gut inflammation and disturbing intestinal mucosal barrier. Recently, a microbiota-based strategy is an attractive paradigm for IBD therapy. Here, we explored the therapeutic potential of tungsten oxide nanoparticles (WO3NPs) against DSS-induced acute colitis mice. WO3NPs (47.9 nm in diameter) significantly reduced intestinal inflammation, attenuated bacterial translocation, restored the colonic epithelium barriers, and remodeled gut microbiota homeostasis in inflamed colon, compared with the free tungsten (sodium tungstate). The element quantification and mapping results showed WO3NPs could increase the adherence of tungsten with Enterobacteriaceae in colonic mucus layer, which inhibited Enterobacteriaceae growth by microbial metabolic reprogramming and ameliorate colitis. This nano-enabled approach for tungsten reduced its deposition in the main organ except for the colon thereby improve the therapeutic efficacy with good biosafety. Together, our results provide insights into the potential nanotherapeutics of WO3NPs against the invasion processes of microbiota in the treatment of IBD.

The colonic mucus barrier is commonly described as a continuous double layer covering the epithelium, separating the microbiota from the intestinal tissue. This model is currently considered valid throughout the colon. The colon is characterised by regional anatomo-functional specificities such as presence and consistency of contents and location. In this study, we characterised the organisation of the colonic mucus barrier in proximal and distal colon of rodents by histological and FISH staining, taking into account aforementioned specificities. By using longitudinal sections and imaging extensive areas of tissue with and without colonic contents, we have obtained a spatiotemporal overview of mucus organisation in the colon. We describe for the first time that the colonic mucus layer covers the faeces instead of the epithelium in the distal colon. This faecal mucus layer confines the microbiota to the faeces and prevents it from remaining in empty distal colon. In the proximal colon, the mucus did not form a separating layer between bacteria and epithelium. We conclude that the organisation of colonic mucus is reliant on the presence of the colonic content, and the location within the colon. Our findings reopen the discussion on the nature of the colonic mucus barrier.

Systems consisting of a polyelectrolyte solution in contact with a cross-linked polyelectrolyte network are ubiquitous (e.g., biofilms, drug-delivering hydrogels, and mammalian extracellular matrices), yet the underlying physics governing these interactions is not well understood. Here, we find that carboxymethyl cellulose, a polyelectrolyte commonly found in processed foods and associated with inflammation and obesity, compresses the colonic mucus hydrogel (a key regulator of host–microbe interactions and a protective barrier) in mice. The extent of this polyelectrolyte-induced compression is enhanced by the degree of polymer negative charge. Through animal experiments and numerical calculations, we find that this phenomenon can be described by a Donnan mechanism. Further, the observed behavior can be quantitatively described by a simple, one-parameter model. This work suggests that polymer charge should be considered when developing food products because of its potential role in modulating the protective properties of colonic mucus.

Intestinal barrier injury is recognized as the main reason for ulcerative colitis (UC) which is a chronic inflammatory disease and the effective therapeutic methods remain limited. In this study, we explored the protection effects of naringenin, nobiletin and hesperetin from Citrus aurantium on colonic mucus layer integrity. The UC mice model was induced by trinitrobenzenesulfonic acid (TNBS). Forty mg/kg/day of naringenin, nobiletin and hesperetin were administrated orally for 7 and 3 days before and after TNBS treatment. Then body weight, disease activity index (DAI) score and colon length were recorded. Colons were collected for immunofluorescence, RT-PCR and western blot assay. Lipopolysaccharide (LPS)-induced cell-co-culture system of Caco-2 and RAW264.7 cells were used to determine activities on protecting intestinal epithelial monolayers damage. Our results showed that Naringenin, nobiletin and hesperetin alleviated body weight loss and colon shortness, decreased DAI score, and up-regulated claudin-2, occludin and zona occludens-1 (ZO-1) expression significantly. Meanwhile, the flavonoids enhanced trans epithelial electric resistance, decreased the permeability and up-regulated occludin and ZO-1 expression in LPS-damaged epithelial monolayers system. Hence, Naringnien, nobiletin and hesperetin show the regulatory effect on UC by protecting colonic mucosa layer integrity. It is suggested the flavonoids may be new supplements for the treatment of UC.

Human 3-dimensional (3D) enteroid or colonoid cultures derived from crypt base stem cells are currently the most advanced ex vivo model of the intestinal epithelium. Due to their closed structures and significant supporting extracellular matrix, 3D cultures are not ideal for host-pathogen studies. Enteroids or colonoids can be grown as epithelial monolayers on permeable tissue culture membranes to allow manipulation of both luminal and basolateral cell surfaces and accompanying fluids. This enhanced luminal surface accessibility facilitates modeling bacterial-host epithelial interactions such as the mucus-degrading ability of enterohemorrhagic E. coli (EHEC) on colonic epithelium. A method for 3D culture fragmentation, monolayer seeding, and transepithelial electrical resistance (TER) measurements to monitor the progress towards confluency and differentiation are described. Colonoid monolayer differentiation yields secreted mucus that can be studied by the immunofluorescence or immunoblotting techniques. More generally, enteroid or colonoid monolayers enable a physiologically-relevant platform to evaluate specific cell populations that may be targeted by pathogenic or commensal microbiota.

Microbiota Mammals accommodate a dense community of metabolically active microorganisms in their gut. This is not a passive relationship, and host and microbe have antagonistic as well as mutualistic responses to each other. Using a whole-colon imaging method in mice, Bergstrom et al. looked at the role of colonic mucus in segregating the microbiota from host cells during elimination of feces (see the Perspective by Birchenough and Johansson). Host goblet cells synthesize two forms of mucin that differ in branched chain O-glycosylation and the site of production in the colon. A “thick” mucus in the proximal, ascending colon wraps the microbiota to form fecal pellets. Transit along the distal, descending colon is lubricated by “thin” mucus that transiently links with the thick mucus. Normal mucus encapsulation prevents inflammation and hyperplasia and thus is important for maintenance of a healthy gut. Science , this issue p. [467][1]; see also p. [402][2] [1]: /lookup/doi/10.1126/science.aay7367 [2]: /lookup/doi/10.1126/science.abe7194

International audience; Streptococcus gallolyticus is a commensal bacterium responsible for infectious endocarditis in the elderly, which has frequently been associated with colonic carcinoma. Whether this species is a cause or a consequence of colorectal cancer remains unknown. We recently demonstrated that S. gallolyticus Pil3 pilus is required for adhesion to colonic mucus and for colonization of mouse distal colon. We show here that Pil3 pilus binds equally well to human colonic mucins derived from HT29-MTX cells and to human stomach mucins from healthy donors. In addition, we have found that Pil3 also binds to human fibrinogen, which expands the repertoire of Pil3 host ligands.

It has long been acknowledged that dietary fibres are important to maintain a healthy gut. Over the past decade, several studies have shown that loss of complex polysaccharides from the Western diet has resulted in alterations to our colonic microbiota. The concurrent increase in the incidence of inflammatory bowel disease in the Western world has driven us to explore the potential mechanistic link between diet, the microbiota and the host defence systems that normally prevent inflammation. Using mice fed a low fibre Western-style diet and robust live tissue analytical methods we have now provided evidence that this diet impairs the colonic inner mucus layer that normally separates bacteria from host cells. Western societies urgently need to develop their understanding of the molecular mechanisms of the diet-microbiota-mucus axis and its implications for inflammatory diseases.

The aim of this study was to evaluate the changes in expression of mucins (MUC2, MUC 3, MUC 4) and trefoil peptide (TFF3) of colonic mucus barrier in patients with ulcerative colitis (UC). 49 patients with left-side UC in the acute stage were examined. All patients underwent endoscopic examination of colonic mucosa with biopsy and morphological study of biopsy sample, determination of expression of MUC2, MUC3, MUC4, TFF3. Changes in colonic mucus barrier of patients with UC indicate disorder in mucus production, expression of mucins and their properties, as well as severity of UC., Целью данной работы была оценка изменений экспрессии муцинов (MUC2, MUC3, MUC4) и трефоилового пептида (TFF3) слизистого барьера кишечника у больных неспецифическим язвенным колитом (НЯК). Было обследовано 49 больных с левосторонним НЯК в стадии обострения. Всем больным НЯК было проведено эндоскопическое исследование с биопсией слизистой оболочки толстой кишки и морфологическим исследованием биоптата, определением экспрессии MUC2, MUC3, MUC4, TFF3. Изменения слизистого барьера кишечника у больных НЯК отображают нарушение процессов слизеобразования, экспрессии муцинов и их свойств, а также тяжесть течения НЯК, Метою цієї роботи була оцінка змін експресії муцинів (MUC2, MUC3, MUC4) і трефоїлового пептиду (TFF3) слизового бар’єру кишечника у хворих на неспецифічний виразковий коліт (НВК). Було обстежено 49 хворих із лівобічним НВК у стадії загострення. Усім хворим на НВК було проведено ендоскопічне дослідження з біопсією слизової оболонки товстої кишки та морфологічним дослідженням біоптату, визначенням експресії MUC2, MUC3, MUC4, TFF3. Зміни слизового бар’єру кишечника у хворих на НВК відображають порушення процесів слизоутворення, експресії муцинів та їх властивостей і тяжкість перебігу НВК.

Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host-microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer-mucus interactions can be described using a thermodynamic model based on Flory-Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice-whose microbiota degrade gut polymers-did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes.

TMF/ARA160 is a Golgi-associated protein with several cellular functions, among them direction of the NF-κB subunit, p65 RelA, to ubiquitination and proteasomal degradation in stressed cells. We sought to investigate the role of TMF/ARA160 under imposed stress conditions in vivo. TMF(-/-) and wild-type (WT) mice were treated with the ulcerative agent dextran sulfate sodium (DSS), and the severity of the inflicted acute colitis was determined. TMF(-/-) mice were found to be significantly less susceptible to DSS-induced colitis, with profoundly less bacterial penetration into the colonic epithelia. Surprisingly, unlike in WT mice, no bacterial colonies were visualized in colons of healthy untreated TMF(-/-) mice, indicating the constitutive resistance of TMF(-/-) colonic mucus to bacterial retention and penetration. Gene expression analysis of colon tissues from unchallenged TMF(-/-) mice revealed 5-fold elevated transcription of the muc2 gene, which encodes the major component of the colonic mucus gel, the MUC2 mucin. Accordingly, the morphology of the colonic mucus in TMF(-/-) mice was found to differ from the mucus structure in WT colons. The NF-κB subunit, p65, a well known transcription inducer of muc2, was up-regulated significantly in TMF(-/-) intestinal epithelial cells. However, this did not cause spontaneous inflammation or increased colonic crypt cell proliferation. Collectively, our findings demonstrate that absence of TMF/ARA160 renders the colonic mucus refractory to bacterial colonization and the large intestine less susceptible to the onset of colitis.

Summary Background: The colon is covered by a mucus barrier that protects the underlying mucosa and alterations in this mucus barrier have been implicated in the aetiology of inflammatory bowel disease (IBD). This study investigated the thickness and continuity of the mucus barrier in ulcerative colitis (UC) and Crohn’s disease (CD) in comparison to normal controls. Methods: Rectal biopsies were taken from 59 patients and cryostat sections stained with periodic acid-Schiff’s/Alcian blue to visualise the mucus layer. Mucus thickness and continuity and goblet cell density were measured using light microscopy. Results: An essentially continuous adherent mucus layer was observed in normal human rectum and there was no change in the mucus barrier in quiescent UC. In active UC there was a trend for the mucus layer to become progressively thinner and significantly more discontinuous as disease severity increased. In severe active UC the mucus layer thickness and goblet cell density were significantly reduced compared with normal controls while the percentage discontinuity significantly increased. Conclusion: It is not until severe UC that there is a global change in mucosal protection as a consequence of large regions lacking mucus, a decrease in secretory potential caused by a loss of goblet cells and a thinner, less effective mucus layer even when it is present.

The colon is subjected to a myriad of potentially damaging agents that may reside within the lumen for 1–2 d. Its first line of defence against these agents is the protective mucus bilayer that lines the entire colonic mucosa. This bilayer acts as a physical barrier to mucosal aggressors and also reduces shear stress to the mucosa. These actions are dependent on the unstimulated (‘resting’) colonic mucus thickness, and also on the rate that this layer can be replenished. The colonic mucus layer is altered in a number of colonic diseases that have been linked to a deficiency of fibre in the diet. The action of fibre intake on colonic mucus thickness and secretion is unknown. Using an in vivo rat model it has been demonstrated that: (1) fibre deficiency leads to a decreased protective potential of the mucus layer (e.g. the mean resting mucus thickness of the fibre-deficient group (429 μm) was significantly lower than its respective control (579 μm; P< 0.001), as was its total mucus secretion over 6 h (270 μm v. 541 μm; Pv. 463 μm). Analysis of the diets suggested a necessity for both soluble and insoluble fibre types in the diet to increase mucosal protection.

防御因子としての大腸粘液の重要性を明らかにするために, 雑種成犬12頭に慢性拘束ストレス負荷実験を行い, 消化管粘膜における粘液糖蛋白質の指標となる粘膜ヘキソサミン濃度を測定し, 大腸粘膜の粘液糖蛋白質量の変化を検討した.さらにストレスを継続しながら, 粘液合成・分泌促進作用を有するテプレノンを経口投与し, 投与後の大腸粘膜の粘液糖蛋白質量の変化を検討した.その結果, ストレス負荷によりイヌの大腸粘液糖蛋白質量は低下し, 大腸に粘膜病変を形成する傾向を認めた.またテプレノンは大腸粘液糖蛋白質の分泌を促進させ, 粘膜病変の形成を抑制する傾向を認めた.以上より, 大腸粘液は大腸粘膜を保護する防御因子として非常に重要であり, ストレス負荷により減少し, テプレノン投与により増加することが示唆された。

大腸粘膜における局所の免疫反応時のmucus release (粘液放出)について検討した.先に著者らは,経直腸的にBSA (bovine serum albumin)による免疫を繰り返した後,免疫対応または非対応抗原で経直腸的challengeを行った場合,ラットの正常大腸の免疫反応に際して,大腸goblet cellmucus (杯細胞粘液)の放出の増加はみられず,正常粘膜では小腸と大腸の局所的抗原抗体反応に差異があることを報告した.今回は,免疫前に経直腸的にホルマリン注入による粘膜障害を行い,腸管粘膜の破綻を来した場合の大腸の局所免疫反応に際して,粘液放出現象の動態について検討を行った.その結果,大腸の粘膜障害時には,大腸局所で抗原抗体反応に依存してmucus releaseの増加がみられ, mucosal barrierを破る機序さえ働けば,局所免疫反応によるmucus releaseが増加することが判明した.

大腸粘膜における局所の免疫反応時のmucus release (粘液放出)について検討した.小腸を場とした抗原抗体反応では,経十二指腸的に動物に抗原を投与し,同一抗原でchallengeしたときに, mucus releaseが正常小腸で増加するというLake A, M.,らの報告がある.これに対して著者らは,ラットの正常大腸粘膜に経直腸的にBSA (bovine serum albumine)による免疫を繰り返した後,免疫対応または非対応抗原で経直腸的challengeを行い,抗原抗体反応によるmucus releaseについて検討した.その結果,小腸と異なり正常大腸では局所免疫で, mucus releaseの増加は対照と差がみられず,正常粘膜では小腸と大腸の局所的抗原抗体反応に差異があることが判明した.

The colonic mucus barrier is the first line of defence that the underlying mucosa has against the wide range of potentially damaging agents of microbial, endogenous, and dietary origin that occur within the colonic lumen. The functional component of mucus is the secreted, polymeric glycoprotein mucin. The mucus barrier can either act as an energy source or a support medium for growth to the intestinal microflora. The mucus barrier appears to effectively partition the vast number of microbial cells from the underlying epithelium. The normal functionality and biochemistry of this mucus barrier appears to be lost in diseases of the colorectal mucosa. Germ-free animal studies have highlighted the necessity of the presence of the colonic microflora to drive the maturation of the colonic mucosa and normal mucus production. A number of by-products of the microflora have been suggested to be key luminal drivers of colonic mucus secretion.

This study examined Na+/H+ ion exchange of caecal and colonic mucus. Two distinct Na+/H+ ion exchange populations of caecal mucus were identified, one group being a cation exchanger and the other an anion exchanger, suggesting that caecal mucus has ampholyte properties responsive to changing physical and chemical properties of luminal contents. Mucus from the colon was consistently an anionic exchanger--this may aid water and electrolyte absorption in the colon. When mucus was incubated with sodium butyrate, the Na+/H+ ion exchange properties of the mucus were decreased.

A new method for preparing an isolated colonic loop in a living rabbit is described. The loop with its intact neurovascular supply can be used as as a "living test tube" to study the adherence of microorganisms to intestinal mucosa. Moreover, the clear colonic mucus produced by the loop can be used to study its physiochemical nature and protecting properties in health and disease.

e14514 Background: As a global epigenetic change, LINE-1 hypomethylation in normal mucosa were reported to have a key role in forming a ‘field defect’ in colorectal carcinogenesis. We aimed to stud...