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Simple Summary: The presence of Bacteroidetes and Fusobacteria phyla are reported to decrease in dogs with chronic enteropathies, likely due to increased oxidative stress in the colon's inflammatory environment. Adherence to the colonic mucosa is considered an essential step for these bacteria to colonize and interact with the host's epithelium and immune system. No studies on dogs have investigated the adhesion of Bacteroides vulgatus and Fusobacterium varium on paraffin-embedded canine colonic mucosa. This study aims to examine the adhesion capacities of these bacterial species to paraffin-embedded colonic mucosa from healthy dogs and investigate their hydrophobicity properties to determine if this factor explains differences in adhesion capability. The results indicated that both canine B. vulgatus and F. varium adhered in high numbers to canine colonic mucosa; however, B. vulgatus had higher hydrophobicity but adhered in lower numbers than F. varium. In conclusion, both bacteria have probiotic potential, but further research is necessary to determine the efficacy and safety of the strains to be used, and other factors influencing attachment beyond hydrophobicity. The relative abundances of Bacteroidetes and Fusobacteria phyla have been reported to be decreased in dogs with chronic enteropathies. In colitis, obligate anaerobes (e.g., Bacteroides and Fusobacterium) are likely to vanish in response to the heightened oxidative stress in the colon's inflammatory environment. The ability to adhere to the colonic mucosa is viewed as an essential step for obligate anaerobic bacteria to colonize and subsequently interact with the host's epithelium and immune system. The reintroduction of a balanced community of obligate anaerobic bacteria using probiotics can restore the microbial function in the intestine. We found no studies on dogs regarding the adhesion properties of Bacteriodes vulgatus and Fusobacterium varium on paraffin-embedded canine colonic mucosa. Thus, the objective of this study is to investigate the adhesion capacities of these two bacterial species to paraffin-embedded colonic mucosa from healthy dogs. Additionally, we investigated their hydrophobicity properties to determine whether differences in adhesion capability can be explained by this factor. The results of our study showed that B. vulgatus adhered significantly lower than F. varium to the canine colonic mucosa (p = 0.002); however, B. vulgatus showed higher hydrophobicity (46.1%) than F. varium (12.6%). In conclusion, both bacteria have potential as probiotics, but further studies will be required to determine the efficacy and safety of the strains to be used, which strains to use, and the reasons other than hydrophobicity for attachment. [ABSTRACT FROM AUTHOR]

Objectives: Cold snare polypectomy (CSP)‐dedicated snares (DSs) may have a higher resection ability than conventional snares. However, a model that can accurately and objectively evaluate and compare the resection ability of each snare has yet to be determined, and characteristics of snare parts that increase resection ability remain unknown. Therefore, we elucidated DSs' resection ability and all characteristics of the parts required for acquiring high resection ability. Methods: An ex vivo model for evaluating resection ability was generated using human colons obtained from forensic autopsy specimens. The force required to resect a 15 mm wide human colonic mucosa (FRR) was measured using this model; if the FRR is small, the resection ability is high. Next, after measuring the stiffness of each snare part, the correlation between the stiffness and resection ability was analyzed. Results: The force required to resect using SnareMaster Plus, Micro‐Tech Cold Snare, Captivator Cold, Exacto Cold Snare, or Captivator II was 13.6 ± 1.0, 12.5 ± 1.2, 7.4 ± 1.2, 6.5 ± 1.0, and 28.7 ± 3.7 N, respectively. All DSs had significantly lower FRR than the conventional snare (Captivator II) and had higher resection ability (P < 0.001). A negative correlation was found between FRR and sheath or wire spindle stiffness, with correlation coefficients of 0.72 (P = 0.042) or 0.94 (P < 0.001), respectively. Moreover, 1 × 7 type wire rings had significantly higher friction coefficients than 1 × 3 type wire rings (P < 0.002). Conclusion: Sheath and wire spindle stiffness should be increased to increase resection ability; 1 × 7 type wire rings may be suitable for CSP‐snare parts. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, the physiological effects of repeated – but not recent – antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilizing bacteria, including Akkermansia muciniphila and Bacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterized by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our proof-of-concept study suggests that long-term antibiotic use in humans can result in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.

The relative abundances of Bacteroidetes and Fusobacteria phyla have been reported to be decreased in dogs with chronic enteropathies. In colitis, obligate anaerobes (e.g., Bacteroides and Fusobacterium) are likely to vanish in response to the heightened oxidative stress in the colon’s inflammatory environment. The ability to adhere to the colonic mucosa is viewed as an essential step for obligate anaerobic bacteria to colonize and subsequently interact with the host’s epithelium and immune system. The reintroduction of a balanced community of obligate anaerobic bacteria using probiotics can restore the microbial function in the intestine. We found no studies on dogs regarding the adhesion properties of Bacteriodes vulgatus and Fusobacterium varium on paraffin-embedded canine colonic mucosa. Thus, the objective of this study is to investigate the adhesion capacities of these two bacterial species to paraffin-embedded colonic mucosa from healthy dogs. Additionally, we investigated their hydrophobicity properties to determine whether differences in adhesion capability can be explained by this factor. The results of our study showed that B. vulgatus adhered significantly lower than F. varium to the canine colonic mucosa (p = 0.002); however, B. vulgatus showed higher hydrophobicity (46.1%) than F. varium (12.6%). In conclusion, both bacteria have potential as probiotics, but further studies will be required to determine the efficacy and safety of the strains to be used, which strains to use, and the reasons other than hydrophobicity for attachment.

In this paper, a new protocol is described, based on solid phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC-MS), to monitor ex vivo changes in endogenous volatile organic compounds (VOCs) released by surgically resected colonic tissues (normal colonic mucosa and adenomatous polyps) from seven patients undergoing operative colonoscopy to identify their molecular pattern. The exhalated volatile organic molecules from these patients were sampled by the ReCIVA® breath sampler, shortly before surgery, and analyzed by GC-MS. Comparing VOC patterns identified in the tissues and in the breath of the same patients, a possible correlation can be found between the levels of methylbenzene and benzaldehyde exhaled and the presence of colonic adenomatous polypoid lesions. [ABSTRACT FROM AUTHOR]

High-grain diet is commonly used in intensive production to boost yield in short term, which may cause adverse effects such as rumen and colonic acidosis in ruminants. Maize is one of the key components of high-grain diet, and different processing methods of maize affect the digestive absorption and gastrointestinal development of ruminants. To investigate the effects of maize form in high-grain diets on colonic fermentation and bacterial community of weaned lambs, twenty-two 2.5-month-old healthy Hu lambs were fed separately a maize meal low-grain diet (19.2% grain; CON), a maize meal high-grain diet (50.4% grain; CM), and a whole maize high-grain diet (50.4% grain; CG). After 7 weeks of feeding, the total volatile fatty acid concentration (P = 0.035) were significantly higher in lambs from CM than that from CON. The sequencing results of colonic content microbial composition revealed that the relative abundance of genera Parasutterella (P = 0.028), Comamonas (P = 0.031), Butyricicoccus (P = 0.049), and Olsenella (P = 0.010) were higher in CM than those in CON; compared with CM, the CG diet had the higher relative abundance of genera Bacteroides (P = 0.024) and Angelakisella (P = 0.020), while the lower relative abundance of genera Olsenella (P = 0.031) and Paraprevotella (P = 0.006). For colonic mucosal microbiota, the relative abundance of genera Duncaniella (P = 0.024), Succiniclasticum (P = 0.044), and Comamonas (P = 0.012) were significantly higher in CM than those in CON. In comparison, the relative abundance of genera Alistipes (P = 0.020) and Campylobacter (P = 0.017) were significantly lower. And the relative abundance of genera Colidextribacter (P = 0.005), Duncaniella (P = 0.032), Christensenella (P = 0.042), and Lawsonibacter (P = 0.018) were increased in the CG than those in the CM. Furthermore, the CG downregulated the relative abundance of genes encoding infectious-disease-parasitic (P = 0.049), cancer-specific-types (P = 0.049), and neurodegenerative-disease (P = 0.037) in colonic microbiota than those in the CM. Overall, these results indicated that maize with different grain sizes might influence the colonic health of weaned lambs by altering the composition of the colonic bacterial community. [ABSTRACT FROM AUTHOR]

In this paper, a new protocol is described, based on solid phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC-MS), to monitor ex vivo changes in endogenous volatile organic compounds (VOCs) released by surgically resected colonic tissues (normal colonic mucosa and adenomatous polyps) from seven patients undergoing operative colonoscopy to identify their molecular pattern. The exhalated volatile organic molecules from these patients were sampled by the ReCIVA® breath sampler, shortly before surgery, and analyzed by GC-MS. Comparing VOC patterns identified in the tissues and in the breath of the same patients, a possible correlation can be found between the levels of methylbenzene and benzaldehyde exhaled and the presence of colonic adenomatous polypoid lesions.

Da-Huan Li,1,* Xue-Ying Liu,1,* Chao Huang,2 Chao-Nan Deng,3 Jia-Lu Zhang,1 Xiao-Wen Xu,1 Liang-Bi Xu1 1Department of the Digestive Endoscopy, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550000, People’s Republic of China; 2Department of the Emergency, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550000, People’s Republic of China; 3Department of the Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang-Bi XuDepartment of the Digestive Endoscopy, The Affiliated Hospital of Guizhou Medical University, No. 28 of Guiyi Street, Yunyan District, Guiyang, 550000, People’s Republic of ChinaTel +8615685178740Fax +86085186774297Email xuliangbi88_dr@163.comObjective: This study aims to analyze the endoscopic and pathological characteristics of colorectal laterally spreading tumors (LSTs) to assist malignant risk stratification to inform selection of the appropriate treatment strategy.Methods: Patients with colorectal LST were selected as retrospective study objects. Characteristics, including endoscopic findings and the most common site of LSTs of different diameters and histological types, were analyzed. The risk factors for malignancy in colorectal LST were explored by multivariate logistic regression analysis.Results: LSTs with diameters of ≥ 20 mm were found mainly in the rectum and mainly with granular-mixed (G-M) morphology (36% and 44.6%, respectively; p < 0.05), while LSTs with diameters of < 20 mm were found mainly in the ascending colon and mainly with granular-homogenous (G-H) morphology (40.9% and 46.2%, respectively; p < 0.05). Adenoma was the main histological type in patients with tumors of all diameters. However, the cancerization rate of LSTs was 31% in patients with tumor diameter ≥ 20 mm, while there was no invasive cancer in patients with tumor diameter < 20 mm. In the low-grade dysphasia (adenoma) group, most of the lesions were located in the ascending colon and most had the morphology LST-G-H (35.8% and 39.2%, respectively; p < 0.05). In the cancerization group, most of the lesions were located in the rectum, with the morphology LST-G-M (51.6% and 67.2%, respectively; p < 0.05), and the diameter was larger than that of the adenoma group (33.84 ± 17.99 mm vs 21.68 ± 8.99 mm).Conclusion: The rectum was the most common site for an LST with a diameter ≥ 20 mm and cancerization, of which the morphology was mainly LST-G-M (endoscopic submucosal dissection is the preferred treatment for this type of LST). LST malignancy was found to be correlated with lesion diameter, location, and morphological appearance.Keywords: colorectal laterally spreading tumors, colonic mucosa, colonoscopy, pathological features, malignant tumor

Abstract Objective The aim of this study was to detect the expression of interleukin (IL)-1β and transforming growth factor (TGF)-β1 in the colonic tissue and serum of irritable bowel syndrome (IBS) rats, as well as the distribution and expression of corticotropin-releasing factor (CRF) in the spinal cord and brain of the visceral hypersensitivity rats, thus to ascertain the mechanism of visceral hypersensitivity signal conduction pathway. Methods The expression of IL-1β and TGF-β1 in the colonic tissue and serum of IBS rats was screened by the liquid chip technology and verified by RT-PCR technology. Then the quantitative analysis of CRF in the spinal cord and brain was achieved by the immunohistochemical method and computerized image system. Result The rat model with visceral hypersensitivity was successfully established. Among the screened indicators of IL-1β and TGF-β1 in colon tissue and serum, only the expression of IL-1β in the model group was up-regulated (P

Ulcerative colitis is a risk factor for colorectal carcinoma. Different mechanisms are related to colitis like apoptosis and hyperproliferation. Moringa oleifera leaves extract (MO) provides a promising option to overcome the risk. To examine the colonic changes in a rat model of colitis induced by sodium nitrate (SN) and study the effects of MO. Eight adult male rats were allocated in each of the three group; control (distilled water), SN (100 mg/kg/day, orally via gastric gavage), and SN + MO (100 mg/kg/day, orally via gastric gavage). Body weight was measured after the end of the experiment. Colonic homogenates were tested for levels of oxidative stress indicators. Immunohistochemistry for P53, PCNA and Ki-67 was performed. Fresh colon specimens were used for quantitative real-time PCR for assessment of P53, PCNA and Ki-67 gene expression. SN group revealed a significant decreased weight (p = 0.002). MDA and NO levels were higher with SN administration than with MO co-administration (p= 0.04, 0.01 respectively). GSH level was reduced in SN group (p = 0.02) and significantly increased with MO intake (p = 0.04). SN-induced colonic destructive changes were reversed with MO. P53, PCNA and Ki-67 levels of gene expression were reduced in SN + MO group than SN group (P = 0.007, 0.02, 0.001 respectively). MO protected the colonic mucosa against SN-induced changes regulating apoptosis, and cell proliferation. • Moringa oleifera has an ameliorating effect against sodium nitrate-induced colitis. • Moringa oleifera can inhibit oxidative stress, apoptosis, and hyperproliferation in the colon. • Moringa oleifera administration produced recovery in the mucous secretions of the colonic goblet cells. • The distorted colonic architecture is preserved after Moringa oleifera administration. [ABSTRACT FROM AUTHOR]

BackgroundCarrying excess body weight is a strong risk factor for colorectal cancer (CRC) development with ~11% of CRC cases in Europe linked to being overweight. The mechanisms through which excess body weight influences CRC development are not well understood but studies suggest the involvement of the presence of chronic low-grade inflammation and changes in the gut microbiota are involved.AimTo compare the mucosal associated microbiota of patients with CRC to understand whether carrying excess body weight was associated with a unique CRC microbial signature.MethodsMicrobiota signatures from colonic mucosal biopsies of CRC lesions and adjacent normal mucosal samples from 20 patients with overt CRC were compared with 11 healthy controls to see if having a BMI of >25 kg/m2 influenced colonic microbial composition.ResultsColonic mucosa samples from patients with CRC confirmed previously reported over-abundance of Fusobacteria associated with CRC but also an increase in Fusobacteria and Prevotella were associated with a BMI of >25 kg/m2. Correlation analysis of bacterial taxa indicated co-exclusive relationships were more common in CRC patients with a BMI >25 kg/m2 with an increase in transphylum relationships also seen in this patient group.ConclusionsThe findings suggest that gut microbiota composition in patients with CRC is influenced by BMI status. Further understanding/defining these differences will provide valuable information in terms of developing novel pre-onset screening and providing post-manifestation therapeutic intervention.

Background: The role of Epstein–Barr virus (EBV) in inflammatory bowel disease (IBD) remains to be elucidated. The aim of this study was to investigate the presence of EBV in the blood and intestinal mucosa of patients with IBD and evaluate the association between EBV positivity and IBD. Methods: Patients with IBD, hospitalized between January 2015 and April 2018, were enrolled. The EBV-DNA load in blood samples from each subject was analyzed by quantitative real-time polymerase chain reaction. EBV-encoded small-RNA 1 (EBER-1) was detected by in-situ hybridization in intestinal mucosa tissue sections of patients with IBD. Result: EBV-DNA was detected in 48 out of 568 patients with IBD (8.4%), and EBER-1 positivity was detected in 27 of these patients (56.3%). Refractory IBD and severe mucosal inflammation were more common in patients with detectable levels of EBER-1 than in those without; the number of EBER-1-positive cells positively correlated with mucosal inflammation (P value < 0.05). Age (≥60 years old) and use of azathioprine were risk factors for EBV infection. There was no significant difference in clinical remission rate and surgical rate between the EBER-1 positive group and EBER-1 negative group, antiviral group and the non-antiviral group, among IBD patients who tested positive for EBV-DNA. Conclusion: Elderly patients with IBD, treated with azathioprine, are more susceptible to EBV positivity. Further, EBV mucosal detection correlated with the severity of mucosal damage and refractoriness, but not prognosis.

Organoid culture provides a powerful technology that can bridge the gap between monolayer cell culture on the one hand and whole animal or human subject research on the other. Tissues from many different organs from multiple species, including human, have already been successfully adapted to organoid growth. While optimal culture conditions have not yet been established for all tissue types, it seems that most tissues will, ultimately, be amenable to this type of culture. The colon is one of the tissues in which organoid culture was first established as a technology and which has been most successfully employed. The ready availability of histologically normal tissue as well as both premalignant and malignant tissue (often from the same individual) makes this possible. While individual tumors are highly variable relative to one another in organoid culture, a high degree of genotypic consistency exists between the tumor tissue and the histologically normal counterpart from a given source. Further, source material and tumor tissue in organoid culture demonstrate a high degree of genotypic consistency. Even after 6–9 mo in continuous culture, drift in the mutational profile has been shown to be minimal. Colon tissue maintained in organoid culture, thus, provides a good surrogate for the tissue of origin—a surrogate, however, that is as amenable to intervention with molecular, pharmacological, and immunological approaches as are more-traditionally studied cell lines. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to detect the expression of interleukin (IL)-1β and transforming growth factor (TGF)-β1 in the colonic tissue and serum of irritable bowel syndrome (IBS) rats, as well as the distribution and expression of corticotropin-releasing factor (CRF) in the spinal cord and brain of the visceral hypersensitivity rats, thus to ascertain the mechanism of visceral hypersensitivity signal conduction pathway. Methods: The expression of IL-1β and TGF-β1 in the colonic tissue and serum of IBS rats was screened by the liquid chip technology and verified by RT-PCR technology. Then the quantitative analysis of CRF in the spinal cord and brain was achieved by the immunohistochemical method and computerized image system. Result: The rat model with visceral hypersensitivity was successfully established. Among the screened indicators of IL-1β and TGF-β1 in colon tissue and serum, only the expression of IL-1β in the model group was up-regulated (P < 0.05). The immunohistochemical method showed that CRF was expressed in the spinal cord, hypothalamus, and the third ventricle. The positive index number of the model groups was higher than that of the control group (P < 0.01). Conclusion: From the research, it can be inferred that IL-1β may participate in the pathogenesis mechanism of IBS via regulating the colon function. The increasing expression of CRF linked to stress in the spinal cord, hypothalamus and the third ventricle indicated that it might play an important role in the mechanisms of visceral hypersensitivity signal conduction pathway. [ABSTRACT FROM AUTHOR]

Group 1 Innate Lymphoid Cells (which include Natural Killer cells and ILC1s) aid in gut anti-bacterial defense through the production of IFNγ, which is critical for mobilizing protective responses against enteric pathogens. When intestinal epithelial barrier integrity is compromised, commensal bacteria are likely to translocate from the gut lumen into the lamina propria. Few studies have addressed the mechanisms by which commensal bacteria impact the function of gut Group 1 ILCs, especially ILC1s. Utilizing an in vitro human colonic lamina propria mononuclear cell (LPMC) model, we evaluated Group 1 ILC cytokine and cytolytic protein production in response to a panel of enteric Gram-positive and Gram-negative commensal and pathogenic bacteria. IFNγ-production by NK cells and ILC1s was significantly increased after LPMC exposure to Gram-negative commensal or pathogenic bacteria, but not after exposure to the Gram-positive bacteria commensals tested. Stimulation of IFNγ production from Group 1 ILCs was not through direct recognition of bacteria by NK cells or ILC1s, but rather required accessory cells within the LPMC population. Myeloid dendritic cells generated IL-12p70, IL-18, and IL-1β upon exposure to enteric bacteria and these cytokines contributed to Group 1 ILC production of IFNγ. Furthermore, Gram-negative commensal or pathogenic bacteria induced significant expression of Granzyme B in NK cells and ILC1s. Overall, these data demonstrate that some enteric commensal bacteria indirectly induce inflammatory cytokine production and cytolytic protein expression from human colonic Group 1 ILCs, a process which could contribute to inflammation in the setting of microbial translocation.

Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, the physiological effects of repeated - but not recent - antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilizing bacteria, including Akkermansia muciniphila and Bacteroides fragilis , dominating in the gut. The altered microbiota composition was further characterized by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our proof-of-concept study suggests that long-term antibiotic use in humans can result in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.

Background: The role of Epstein–Barr virus (EBV) in inflammatory bowel disease (IBD) remains to be elucidated. The aim of this study was to investigate the presence of EBV in the blood and intestinal mucosa of patients with IBD and evaluate the association between EBV positivity and IBD. Methods: Patients with IBD, hospitalized between January 2015 and April 2018, were enrolled. The EBV-DNA load in blood samples from each subject was analyzed by quantitative real-time polymerase chain reaction. EBV-encoded small-RNA 1 (EBER-1) was detected by in-situ hybridization in intestinal mucosa tissue sections of patients with IBD. Result: EBV-DNA was detected in 48 out of 568 patients with IBD (8.4%), and EBER-1 positivity was detected in 27 of these patients (56.3%). Refractory IBD and severe mucosal inflammation were more common in patients with detectable levels of EBER-1 than in those without; the number of EBER-1-positive cells positively correlated with mucosal inflammation (P value < 0.05). Age (≥60 years old) and use of azathioprine were risk factors for EBV infection. There was no significant difference in clinical remission rate and surgical rate between the EBER-1 positive group and EBER-1 negative group, antiviral group and the non-antiviral group, among IBD patients who tested positive for EBV-DNA. Conclusion: Elderly patients with IBD, treated with azathioprine, are more susceptible to EBV positivity. Further, EBV mucosal detection correlated with the severity of mucosal damage and refractoriness, but not prognosis. [ABSTRACT FROM AUTHOR]

Inorganic dietary nitrate plays vital roles in biological functions via the exogenous NO3-/NO2-/NO pathway under hypoxia and ischemia. We previously verified the antioxidative effects of inorganic nitrate in a mouse model of total body irradiation (TBI). Accordingly, in this study, we evaluated the effects of inorganic nitrate on prevention of TBI-induced colon injury and dysbiosis of the gut microbiome. Nitrate significantly rescued the abnormal biological indexes (body weight, white blood cell, red blood cell, platelet, hemoglobin level and intestinal canal lengths) induced by TBI. Then, we detected oxidative stress and DNA damage indexes (phospho-histone H2AX and p53 binding protein 1), which were both increased by irradiation (IR) and alleviated by nitrate. IR-induced apoptosis and senescence were ameliorated by inorganic nitrate. The distribution of the gut microbiome differed for mice with TBI and those receiving inorganic nitrate. The average abundance of Lactobacillus significantly increased, and that of Bacteroidales decreased at the genus level in the nitrate group compared with that in the IR alone group. At 30 days after TBI, the abundances of Bacteroides and Faecalibaculum decreased, whereas that of Lactobacillus increased in the IR + nitrate group compared with that in the IR alone group. Inorganic nitrate efficiently prevents TBI-induced colon epithelium injury and maintains the homeostasis of the gut microbiome. Thus, our results showed that inorganic nitrate might be a promising treatment for TBI induced colon injury. Image 1 • We evaluated the effects of inorganic nitrate on TBI-induced colon injury prevention. • Nitrate significantly rescued the abnormal biological indexes induced by TBI. • Oxidative stress and DNA damage were increased by IR and reduced by nitrate. • The gut microbiome differed for mice with TBI and those receiving inorganic nitrate. • Inorganic nitrate prevented TBI-induced colon epithelium injury. [ABSTRACT FROM AUTHOR]

Innate lymphoid cells (ILCs) are a diverse family of cells that play critical roles in mucosal immunity. One subset of the ILC family, Group 3 ILCs (ILC3s), has been shown to aid in gut homeostasis through the production of IL-22. IL-22 promotes gut homeostasis through its functional effect on the epithelial barrier. When gut epithelial barrier integrity is compromised, such as in Human Immunodeficiency Virus (HIV) infection and inflammatory bowel disease (IBD), microbes from the gut lumen translocate into the lamina propria, inducing a multitude of potentially pathogenic immune responses. In murine models of bacterial infection, there is evidence that bacteria can induce pro-inflammatory IFNγ production in ILC3s. However, the impact of diverse translocating bacteria, particularly commensal bacteria, in dictating IFNγ versus IL-22 production by human gut ILC3s remains unclear. Here, we utilized an in vitro human lamina propria mononuclear cell (LPMC) model to evaluate ILC3 cytokine production in response to a panel of enteric Gram-positive and Gram-negative commensal and pathogenic bacteria and determined potential mechanisms by which these cytokine responses were induced. The percentages of IL-22-producing ILC3s, but not IFNγ-producing ILC3s, were significantly increased after LPMC exposure to both Gram-positive and Gram-negative commensal or pathogenic bacterial stimuli. Stimulation of IL-22 production from ILC3s was not through direct recognition of bacterial antigen by ILC3s, but rather required the help of accessory cells within the LPMC population. CD11c+ myeloid dendritic cells generated IL-23 and IL-1β in response to enteric bacteria and contributed to ILC3 production of IL-22. Furthermore, ligation of the natural cytotoxicity receptor NKp44 on ILC3s in response to bacteria stimulation also significantly increased the percentage of IL-22-producing ILC3s. Overall, these data demonstrate that human gut microbiota, including commensal bacteria, indirectly modulate colonic ILC3 function to induce IL-22, but additional signals are likely required to induce IFNγ production by colonic ILC3s in the setting of inflammation and microbial translocation.

Previous studies have compared fecal metabolites from healthy and colorectal cancer (CRC) patients to predict the pro‐CRC signatures. However, the systemic mechanistic link between feces and colonic tissues of CRC patients is still limited. The current study was a paralleled investigation of colonic tumor tissues and their normal adjacent tissues alongside patient‐matched feces by using 1H nuclear magnetic resonance spectroscopy combined with pattern recognition to investigate how fecal metabolic phenotypes are linked to the changes in colorectal tumor profiles. A set of overlapping discriminatory metabolites across feces and tumor tissues of CRC were identified, including elevated levels of lactate, glutamate, alanine, succinate and reduced amounts of butyrate. These changes could indicate the networks for metabolic pathway perturbations in CRC potentially involved in the disruptions of glucose and glycolytic metabolism, TCA cycle, glutaminolysis, and short chain fatty acids metabolism. Furthermore, changes in fecal acetate were positively correlated with alterations of glucose and myo‐inositol in colorectal tumor tissues, implying enhanced energy production for rapid cell proliferation. Compared to other fecal metabolites, acetate demonstrated the highest diagnostic performance for diagnosing CRC, with an AUC of 0.843 in the training set, and a good predictive ability in the validation set. Overall, these associations provide evidence of distinct metabolic signatures and metabolic pathway disturbances between the colonic tissues and feces within the same individual, and changes of fecal metabolic signature could reflect the CRC tissue microenvironment, highlighting the significance of the distinct fecal metabolic profiles as potential novel and noninvasive relevant indicators for CRC detection. What's new? While fecal testing for altered metabolite levels is a promising tool for colorectal cancer (CRC) screening, associations between specific metabolic disturbances and CRC remain unknown. Here, parallel analysis of CRC tissues and adjacent normal tissues and fecal samples obtained pre‐ and post‐operatively from the same patients reveals a link between fecal metabolic phenotype and metabolite changes in CRC. Discriminatory metabolites were detected across feces and CRC tissues. Among these metabolites was fecal acetate, which showed high diagnostic performance for CRC. The findings warrant further investigation of fecal metabolic signature as a non‐invasive means of early CRC detection. [ABSTRACT FROM AUTHOR]

Abstract The application of pristine С 60 fullerene aqueous colloid solution (C 60 FAS; 0.5 mg/kg body weight) for rats experienced acute colitis, either intraperitoneally or intrarectally (1) restores the colonic mucosa healing and epithelial barrier integrity, evidenced by autopsies and histological findings and the normalization of phenolsufonphthalein dye daily excretion; (2) attenuates the consequences of hemorrhages, such as signs of anemia and increased platelet count; (3) improves the liver redox status suppressing the lipid peroxidation (malonic dialdehyde and protein carbonyl group levels tended down) and stimulating the antioxidant defense system (glutathione peroxidase activity grew up). In addition, C 60 FAS intrarectally increases the monocyte count and decreases content of neutrophil granulocytes, i.e. diminishes the rate of the inflammatory process and activates the processes of colon tissues restoring with monocytes involvement. Therefore, intrarectal administration of C 60 FAS may serve as an efficient tool of ulcerative colitis therapy. Graphical abstract Unlabelled Image Highlights • Pristine С 60 fullerenes restore colonic mucosa integrity under acute colitis in rats. • C 60 FAS attenuates the consequences of bowel hemorrhages and inflammation. • C 60 FAS inhibits lipid peroxidation and stimulates antioxidant defense system in liver. [ABSTRACT FROM AUTHOR]

The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC.

Objective. To assess histological changes of colonic mucosa in patients with clinically different types of irritable bowel syndrome (IBS) before and after the treatment with tetracyclic antidepressant and selective serotonin reuptake inhibitor. Methods. Adult patients (over 18 years) with confirmed diagnosis of IBS were examined. Biopsy specimens were taken from colon during colonoscopy for the next histological examination. One expert gastrointestinal pathologist assessed all tissue samples. We patent semi quantitative assessment of the severity of cell infiltration of colonic mucosa, which could be assessed as inflammatory (neutrophils), immune (lymphocytes, plasma cells, macrophages), or allergic (eosinophils) response (0 to 3 degrees). All patients received treatment due to the clinical variant of IBS: 1) IBS-constipation – mirtazapinum 15 mg/night+lactulose 30ml/morning (+30ml/night if needed); 2) IBS-diarrhea – escitalopram 5mg/night+rifaximine 600mg/twice a day; 3) IBS-unspecified – mirtazapinum 15 mg/escitalopram 5mg/ night; 4) IBS-mixed – mirtazapinum 15 mg, lactulose 30ml/morning (+30ml/night if needed) / escitalopram 5mg/night+rifaximine 600mg/twice a day. Results. 107 patients were examined, 36 of them had constipation (I group), 35 – diarrhea (II group), 22- unspecified variant (III group) and 12 patients had mixed variant of IBS (IV group) due to Rome III criteria (2006). 1st degree of lymphocyte infiltration was detected in 100% IBS-constipation patients and in 58,3% IBS-mixed variant (p0.05). No cases of 2nd or 3rd degree of colonic mucosa infiltration were found. Conclusion. After the treatment with tetracyclic antidepressant and selective serotonin reuptake inhibitor we found that the degree of inflammation of colonic mucosa was reduced or disappeared, due to the zero degree of infiltration according to our patented classification. Citation: Nagieva S, Svintsitskyy A, Kuryk O, Korendovych I. [Morphological changes of intestinal mucosa in patients with different clinical variants of irritable bowel syndrome using tetracyclic antidepressants and selective seroto-nin reuptake inhibitor]. Morphologia. 2015;9(4):49-56. Ukrainian.

The aim of this study was to characterize the effects of Maresin 1 (MaR1), a DHA-derived pro-resolving lipid mediator, on obesity-related colonic inflammation and gut dysbiosis in diet-induced obese (DIO) mice. In colonic mucosa of DIO mice, the MaR1 treatment decreased the expression of inflammatory genes, such as Tnf-α and Il-1β. As expected, the DIO mice exhibited significant changes in gut microbiota composition at the phylum, genus, and species levels, with a trend to a higher Firmicutes/Bacteroidetes ratio. Deferribacteres and Synergistetes also increased in the DIO animals. In contrast, these animals exhibited a significant decrease in the content of Cyanobacteria and Actinobacteria. Treatment with MaR1 was not able to reverse the dysbiosis caused by obesity on the most abundant phyla. However, the MaR1 treatment increased the content of P. xylanivorans, which have been considered to be a promising probiotic with healthy effects on gut inflammation. Finally, a positive association was found between the Deferribacteres and Il-1β expression, suggesting that the increase in Deferribacteres observed in obesity could contribute to the overexpression of inflammatory cytokines in the colonic mucosa. In conclusion, MaR1 administration ameliorates the inflammatory state in the colonic mucosa and partially compensates changes on gut microbiota caused by obesity.

Porcine epidemic diarrhea (PED) is a major gastrointestinal disease afflicting suckling pigs that causes huge industrial economic losses. In this study, we investigated microbiota from the colonic mucosa and content in healthy and PED piglets. High-throughput 16S rRNA gene sequencing was performed to identify inter-group differences. Firmicutes, Fusobacteria, Proteobacteria, and Bacteroidetes were the top four affected phyla. The proportion of Proteobacteria was higher in infected than in healthy piglets, and the opposite was observed for Bacteroidetes (more than four-fold higher in the healthy group). In the infected group, Fusobacterium accounted for 36.56% and 21.61% in the colonic mucosa and contents, respectively, while in the healthy group, they comprised 22.53% and 12.67%, respectively. The percentage of Lactobacillus in healthy colons (15.63%) was considerably higher than that in the disease group (

Objectives:To improve understanding of the preclinical stage of colonic inflammation by exploring the existence of a link between early inflammatory changes in the colonic mucosa and the systemic redox balance. Methods:Clinical characteristics, a fasting blood draw, and mucosal biopsies from the right, left, and sigmoid-rectum colonic tracts collected from 28 healthy individuals (14/14 males/females) who underwent colonoscopy. Myeloperoxidase (MPO) positive cells infiltrating colonic mucosa specimens were assessed by immunohistochemistry, and patients divided into high or low MPO expressing cells/optical field groups (MPOhighor MPOlow, respectively).The systemic oxidative balance has been studied through derived-Reactive Oxygen Metabolites (d-ROMs), Biological Antioxidant Potential (BAP), and Lipoperoxide-cholesterol Oxidizing (LP-CHOLOX) tests on serum. Results:MPOhighpatients demonstrated an increased systemic oxidative stress compared to MPOlowindividuals (P = 0.035), especially when MPO is referred to the left-sided colonic mucosa (P = 0.007). MPOlowsubjects in the sigmoid-rectum showed a significant higher antioxidant capacity in the serum (P < 0.02). Sex-specific differences in MPO expression (male and female: 4.6 ± 3.2 and 2.6 ± 1.5 MPO-positive cells/optical field, respectively,P = 0.044), and a decreasing gradient in MPO expression moving from the cecum to the rectum (ascendant, descendant, and sigmoid-rectum: 3.7 ± 2.8, 3.1 ± 1.7, and 1.4 ± 0.5, respectively,P = 0.012) were also found and discussed. Discussion:The study is the first demonstrating a connection between systemic redox balance and MPO expression in the colonic mucosa, according to the colonic tract and patient gender. Further research evaluating the MPO expression in the human colon and its relationship with pathological conditions could benefit from these results. [ABSTRACT FROM AUTHOR]

Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40 nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour. siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine. [ABSTRACT FROM AUTHOR]

The effect of a 5-HT 3 receptor-selective agonist SR57227A was investigated on the outflow of 5-hydroxytryptamine (5-HT) from isolated muscle layer-free mucosal preparations of guinea-pig colon. The mucosal preparations were incubated in vitro and the outflow of 5-HT from these preparations was determined by high-performance liquid chromatography with electrochemical detection. SR57227A (100 μM) produced a tetrodotoxin-resistant and sustained increase in the outflow of 5-HT from the mucosal preparations. The SR57227A-evoked sustained 5-HT outflow was completely inhibited by the 5-HT 3 receptor antagonist ramosetron (1 μM). The neuropeptide Y 1 receptor antagonist BIBO3304 (100 nM) partially inhibited the SR57227A-evoked sustained 5-HT outflow, but the Y 2 receptor antagonist BIIE0246 (1 μM) or the glucagon-like peptide-1 (GLP-1) receptor antagonist exendin-(9−39) (1 μM), showed a minimal effect on the SR57227A-evoked sustained 5-HT outflow. In the presence of BIBO3304 (100 nM) and exendin-(9−39) (1 μM), SR57227A (100 μM) failed to produce a sustained increase in the outflow of 5-HT. The Y 1 receptor agonist [Leu 31 , Pro 34 ]-neuropeptide Y (10 nM), but not GLP-1-(7−36) amide (100 nM), produced a sustained increase in the outflow of 5-HT. We found that 5-HT 3 receptor-triggered 5-HT release from guinea-pig colonic mucosa is mediated by the activation of 5-HT 3 receptors located at endocrine cells (enterochromaffin cells and peptide YY (PYY)-containing endocrine cells). The activation of both Y 1 and GLP-1 receptors appears to be required for the maintenance of 5-HT 3 receptor-triggered 5-HT release. It is therefore considered that 5-HT 3 receptors located at colonic mucosa play a crucial role in paracrine signaling between enterochromaffin cells and PYY-containing endocrine cells. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of starter feeding supplementation on colonic mucosal bacterial communities and on mucosal immune homeostasis in pre-weaned lambs. We selected eight pairs of 10-day-old lamb twins. One twin was fed breast milk (M, n = 8), while the other was fed breast milk plus starter (M+S, n = 8). The lambs were sacrificed at 56 days age. Colonic content was collected to determine the pH and the concentrations of volatile fatty acids (VFA) and lactate. The colonic mucosa was harvested to characterize the bacterial communities using Illumina MiSeq sequencing and to determine mRNA expression levels of cytokines and toll-like receptors (TLR) using quantitative real-time PCR. The results show that starter feeding decreased luminal pH and increased the concentrations of acetate, propionate, butyrate, total VFA, and lactate in the colon. The principal coordinate analysis (PCA) and analysis of molecular variance show that starter feeding supplementation significantly affected the colonic mucosal bacterial communities with a higher relative abundance of the dominant taxa unclassified S24-7, Oscillibacter, Prevotella, Parabacteroides, Bifidobacterium, Ruminobacter, and Succinivibrio, and a lower proportion of unclassified Ruminococcaceae, RC9_gut_group, Blautia, Phocaeicola, Phascolarctobacterium, unclassified BS11_gut_group, unclassified family_XIII, and Campylobacter in lambs. Meanwhile, starter feeding decreased mRNA expression of TLR4 and cytokines TNF-α and IFN-γ in colonic tissue. Furthermore, the changes in the colonic mucosal mRNA expression of TLR and cytokines were associated with changes in mucosal bacterial composition. These findings may provide new insights into colonic mucosal bacteria and immune homeostasis in developing lambs. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Hemomine (HM) is an herbal mixture consisting of 5 varieties of the hematopoietic herbal extracts ( Angelica gigas Nakai, Cnidium officinale Makino, Paeonia lactiflora Pall., Rehmannia glutinosa Liboschitz ex Stueudel, Glycyrrhiza uralensis Fischer). Aim of the study Anemia has been treated with iron supplements, whereas it could cause adverse side effects such as digestive discomfort. In the present study, HM was applied to SHA rats to test for several activities so as to verify its therapeutic potentials on anemia and digestive discomfort. Materials and methods Sprague-Dawley rats were assigned to seven groups: (Two controls, two references (ferric hydroxide polymatose (FM) and ferritin extract glycerin hydrate (FA)), three different concentrations of HM, n=8 per groups), and induced subacute hemorrhagic anemia (SHA) through blood exsanguinations once a day for 7 days. Results The SHA animal model showed changes in the markers related to classic iron-deficient and regenerative anemia in this experiment. However, the SHA related anemic signs were dose-dependently inhibited by the administration of HM 2, 1, and 0.5 ml/kg for 7 days, and more favorably than the equal dosages of FM and FA. In addition, FM and FA showed the typical constipation signs, including reduction of in thickness of the colonic mucosa, in contrast, HM 2, 1, and 0.5 ml/kg groups had no effects on the gastrointestinal motilities and the colonic mucous components when compared to the controls. The results suggested that the HM significantly showed to have therapeutic effects in the experimental SHA in rats, and is more potent than the commercial iron supplement through the proliferation of hematopoietic stem cells with reduced digestive discomfort. Conclusions Therefore, Hemomine may prove to be a promising hematopoietic and therapeutic agent for anemia. [ABSTRACT FROM AUTHOR]

Colonic inflammation is associated with decreased tissue oxygenation, significantly affecting gut homeostasis. However, the crosstalk between O consumption and supply in the inflamed tissue are not fully understood. Using a murine model of colitis, we analysed O in freshly prepared samples of healthy and inflamed colon tissue. We developed protocols for efficient ex vivo staining of mouse distal colon mucosa with a cell-penetrating O sensitive probe Pt-Glc and high-resolution imaging of O concentration in live tissue by confocal phosphorescence lifetime-imaging microscopy (PLIM). Microscopy analysis revealed that Pt-Glc stained mostly the top 50-60 μm layer of the mucosa, with high phosphorescence intensity in epithelial cells. Measured O values in normal mouse tissue ranged between 5 and 35 μM (4-28 Torr), tending to decrease in the deeper tissue areas. Four-day treatment with dextran sulphate sodium (DSS) triggered colon inflammation, as evidenced by an increase in local IL6 and mKC mRNA levels, but did not affect the gross architecture of colonic epithelium. We further observed an increase in oxygenation, partial activation of hypoxia inducible factor (HIF) 1 signalling, and negative trends in pyruvate dehydrogenase activity and O consumption rate in the colitis mucosa, suggesting a decrease in mitochondrial respiration, which is known to be regulated via HIF-1 signalling and pyruvate oxidation rate. These results along with efficient staining with Pt-Glc of rat and human colonic mucosa reveal high potential of PLIM platform as a powerful tool for the high-resolution analysis of the intestinal tissue oxygenation in patients with inflammatory bowel disease and other pathologies, affecting tissue respiration. [ABSTRACT FROM AUTHOR]

One of the typical complaints in the pediatric population is umbilical discharge. Among the congenital causes, remnants of omphalomesenteric duct or patent urachus are often detected. On a few occasions, multiple types of ectopic tissue are present. We describe histopathologic findings of two cases reported recently at our center as pediatric umbilical lesions with associated ectopic tissue. Histopathology of the excised mass confirmed the patent omphalomesenteric duct with ectopic gastric, duodenal, and colonic mucosa and pancreatic tissue in two patients with the clinical presentation of umbilical discharge. There were no associated congenital anomalies in these patients. The presence of multiple ectopic gastrointestinal mucosa and pancreas in the umbilical mass is unusual. Herein, we report these cases because of its rarity, multiple ectopic tissues, and reviewing the literature of the reported cases of multiple ectopic tissues., Competing Interests: None