Traditional Chinese Medicine: A promising strategy to regulate the imbalance of bacterial flora, impaired intestinal barrier and immune function attributed to ulcerative colitis through intestinal microecology.

ETHNOPHARMACOLOGICAL RELEVANCE: Globally, plant materials are widely used as an additional and alternative therapy for the treating of diverse diseases. Ulcerative colitis (UC) is a chronic, recurrent and nonspecific inflammation of the bowel, referred to as "modern intractable disease" according to the World Health Organization. With the continuous development of theoretical research in Traditional Chinese Medicine (TCM) and the advantages of TCM in terms of low side effects, TCM has shown great progress in the research of treating UC. AIM OF THIS REVIEW: This review aimed to explore the correlation between intestinal microbiota and UC, summarize research advances in TCM for treating UC, and discuss the mechanism of action of TCM remedies in regulating intestinal microbiota and repairing damaged intestinal barrier, which will provide a theoretical basis for future studies to elucidate the mechanism of TCM remedies based on gut microbiota and provide novel ideas for the clinical treatment of UC. METHODS: We have collected and collated relevant articles from different scientific databases in recent years on the use of TCM in treating UC in relation to intestinal microecology. Based on the available studies, the therapeutic effects of TCM are analysed and the correlation between the pathogenesis of UC and intestinal microecology is explored. RESULTS: TCM is used to further protect the intestinal epithelium and tight junctions, regulate immunity and intestinal flora by regulating intestinal microecology, thereby achieving the effect of treating UC. Additionally, TCM remedies can effectively increase the abundance of beneficial bacteria that produce short-chain fatty acids, decrease the abundance of pathogenic bacteria, restore the balance of intestinal microbiota, and indirectly alleviate intestinal mucosal immune barrier dysfunction and promote the repair of damaged colorectal mucosa. CONCLUSION: Intestinal microbiota is closely related to UC pathogenesis. The alleviation of intestinal dysbiosis can be a potential novel therapeutic strategy for UC. TCM remedies can exert protective and therapeutic effects on UC through various mechanisms. Although intestinal microbiota can aid in the identification of different TCM syndromes types, further studies are needed using modern medical technology. This will improve the clinical therapeutic efficacy of TCM remedies in UC and promote the application of precision medicine.

Baitouweng decoction repairs the intestinal barrier in DSS-induced colitis mice via regulation of AMPK/mTOR-mediated autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is one of non-specific inflammatory bowel disease that mainly affects the colon. Recently, UC has become a significant social and economic problem worldwide. Baitouweng decoction (BD), a traditional Chinese medicine described in the "Treatise on Febrile Diseases", has been used for centuries to treat intestinal diseases. However, its underlying mechanism remains largely unexplored. AIM OF STUDY: In this study, we aimed to investigate the effect of BD on autophagy for repairing the colonic barrier in DSS-induced colitis mice and explored its role in regulating the autophagic signaling pathway AMPK/mTOR. MATERIALS AND METHODS: Mice with colitis were treated with 3% dextran sulfate sodium (DSS) for 7 days. The effectiveness of BD in treating DSS-induced colitis was evaluated through body weight, disease activity index (DAI), colon length, pathological changes, organ index, and proportion of blood cells. Moreover, intestinal epithelial permeability was analyzed by examining FITC-dextran leakage, the bacterial load of mesenteric lymph nodes (MLNs), and bacterial infiltration of colon tissues. Barrier function was evaluated by assessing the number and proportion of colonic goblet cells and the expression of tight junction proteins, including ZO-1, claudin-1, and occludin. Furthermore, the levels of autophagy were assessed by examining the number of autophagosomes and the expression of the autophagy-related proteins LC3, Beclin1, and P62. Additionally, network pharmacology research was conducted to analyze the potential mechanisms underlying the medicinal effects, as indicated by the role of AMPK/mTOR in regulating the autophagic signaling pathway. RESULTS: BD improved colitis symptoms in mice by restoring body weight and colon length and reducing inflammatory cell infiltration. Additionally, BD decreased the diffusion of FITC-dextran and bacterial translocation in MLNs, as well as bacterial infiltration of the colonic mucosa. The number and proportion of colonic goblet cells, the expression of ZO-1, Claudin-1, and Occludin, and the levels of autophagy were also increased by BD. Network pharmacology analysis suggested that BD might affect intestinal autophagy through the AMPK signaling pathway, which was confirmed by the activation of AMPK phosphorylation and the downregulation of mTOR expression following BD treatment. CONCLUSION: Our study demonstrated that BD repaired the intestinal epithelial barrier in DSS-induced colitis mice by activating AMPK phosphorylation and inhibiting mTOR expression to promote autophagy.

Aqueous M. oleifera leaf extract alleviates DSS-induced colitis in mice through suppression of inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. (M. oleifera) is a perennial deciduous tree with considerable agricultural and pharmacological value. Nearly all parts of the tree are edible, and nearly all parts are used in traditional medicine. Leaves of M. oleifera have the functions of hypoglycemic (antidiabetic), anti-cancer and anti-oxidant stress, but less research pay attention to the anti-inflammatory effect of M. oleifera leaves. AIM OF THE STUDY: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal medication. Here, we investigated the anti-inflammatory effects of aqueous extract of M. oleifera leaves. MATERIALS AND METHODS: Intestinal organoids and mice as in vitro and in vivo models to investigate the effects of aqueous extract of M. oleifera leaves on inflammation induced by TNF-α and dextran sulfate sodium (DSS) respectively. The expression of inflammatory cytokines and proliferation-related genes were evaluated by RT-qPCR, respectively. The compounds in the leaf extract were determined by LC/MS, and network pharmacology approach was employed to predict 54 anti-IBD potential targets of quercetin-3-galactoside (QG) and isoquercitrin (IS). RESULTS: We found that the extract protected against damage to intestinal organoids caused by tumor necrosis factor (TNF-α), and significantly down-regulated the expression of inflammatory cytokines. The extract also suppressed the TNF-α-induced expression of Pcna, c-Myc, and c-Jun. Additionally, oral administration of the extract also ameliorated DSS-induced colon damage (colonic shortening, loss of goblet cells and overall abnormal cellularity), and inhibited the expression of inflammatory cytokines and proliferation-related genes in colitis. By LC/MS we identified nearly 2000 of the compounds in the leaf extract, of the flavonoids identified, QG and IS made up the largest percentage; both have been shown to have anti-inflammatory properties. Moreover, network pharmacology approach was employed to predict 54 anti-IBD potential targets of QG and IS. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the overlapping targets participated in response to oxidative stress and PI3K-Akt signaling pathway respectively. CONCLUSIONS: The present study demonstrated the anti-inflammatory capability, in vitro and in vivo, of the aqueous extract of M. oleifera leaves and suggests its potential phytotherapeutic treatment for IBD.

Methylglyoxal scavenging capacity of fiber-bound polyphenols from highland barley during colonic fermentation and its modulation on methylglyoxal-interfered gut microbiota.

Methylglyoxal (MGO) scavenging capacity of fiber-bound polyphenols from highland barley during colonic fermentation and its potential role in modulating MGO-induced detrimental effects on gut microbiota were studied. Results showed that only 25.3 % of polyphenols were released after 24 h of colonic fermentation. More than 45.5 % of MGO was scavenged by the residual fiber-bound polyphenols in the model system, showing a vital role in scavenging MGO in the colonic lumen compared to the released polyphenols. Moreover, MGO promoted the increase of gut pathogens (Escherichia-Shigella and Klebsiella) and inhibited the proliferation of Megasphaera, Bifidobacterium and Megamonas, as well as reduced short-chain fatty acids (SCFAs) concentration. The addition of fiber-bound polyphenols of highland barley could effectively counteract MGO-induced detrimental consequences on gut microbiota and SCFAs production. These results demonstrate that fiber-bound polyphenols from highland barley can exert beneficial role through scavenging MGO and promises to be a functional ingredient to maintain colon heath.

Sourdough process and spirulina-enrichment can mitigate the limitations of colon fermentation performances of gluten-free breads in non-celiac gut model.

In this work, the impact of gluten free (GF) breads enriched with spirulina on the ecology of the colon microbiota of non-celiac volunteers was investigated. Simulation of digestion of GF breads was conducted with an in vitro gut model. Microbiomics and metabolomics analyses were done during colon fermentations to study the modulation of the microbiota. From the results, a general increase in Proteobacteria and no reduction of detrimental microbial metabolites were observed in any conditions. Notwithstanding, algae enriched sourdough breads showed potential functionalities, as the improvement of some health-related ecological indicators, like i) microbiota eubiosis; ii) production of bioactive volatile organic fatty acids; iii) production of bioactives terpenes. Our results indicate that a sourdough fermentation and algae enrichment can mitigate the negative effect of GF breads on gut microbiota of non-celiac consumers.

Colon Injuries and Infectious Complications in Concurrent Gunshot-Related Fractures.

INTRODUCTION: Concurrent colonic injury among patients with gunshot-related fractures presents a potential risk for infectious complications. We hypothesized that colon injuries are associated with more infectious orthopedic complications among gunshot victims with concurrent fractures. MATERIALS AND METHODS: We reviewed trauma patients arriving at our level 1 trauma center from January 1, 2019 to May 31, 2022 who suffered any gunshot-related fracture and also underwent an exploratory laparotomy. Of these patients, those with colon injuries were compared to those without colon injuries. Baseline characteristics, including antibiotic regimens, were collected in addition to outcomes of length of stay, intensive care unit admission, ventilator requirement, and development of infectious orthopedic complications. RESULTS: Overall, 56 of the 107 included patients had colon injuries. Age, sex, race/ethnicity, and Injury Severity Score were similar between groups. Of patients with colonic injuries, 16.1% received early, repeat dosing of broad-spectrum antibiotics, while only 3.9% of patients without colonic injuries received this antibiotic dosing (P = 0.04). Interestingly, only patients with colon injuries developed infectious orthopedic complications and none of the patients without colon injuries developed such complications (10.7% versus 0.0%, P = 0.03). All patients with orthopedic infections had infected pelvic fractures. Length of stay was 3 d longer in the colon injury group (P = 0.04). There was no difference in intensive care unit admission, ventilator requirement, or death. CONCLUSIONS: Concurrent colon injuries among patients with gunshot-related fractures are associated with higher risk of infectious orthopedic complications, likely from direct spread of fecal contaminant. Early, broad-spectrum antibiotics may be associated with reduced infectious orthopedic complications.

Shen-Ling-Bai-Zhu-San alleviates the imbalance of intestinal homeostasis in dextran sodium sulfate-induced colitis mice by regulating gut microbiota and inhibiting the NLRP3 inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Ling-Bai-Zhu-San (SLBZS) is a classic formula for strengthening the spleen and dispelling dampness, which has shown excellent efficacy in inflammatory bowel disease (IBD) in traditional Chinese medicine clinical studies. However, its exact pharmacological mechanism needs to be further elucidated. AIM OF THE STUDY: This study aims to investigate the restorative effect and mechanism of SLBZS on disturbed intestinal homeostasis in DSS-induced colitis mice. MATERIALS AND METHODS: A colitis model was induced by 3% dextran sulfate sodium (DSS) for seven days, and SLBZS was administered by gavage. The influence of SLBZS on DSS-induced clinical symptoms and disease activity index (DAI) was monitored and analyzed. Alcian blue and fluorescein isothiocyanate-conjugated wheat germ agglutinin (FITC-WGA) staining were used to assess intestinal mucus changes. The expression of intestinal barrier function indexes and immune-associated indexes were determined by H&E staining, real-time quantitative PCR (RT-qPCR), and Western blot. And gut microbiota changes were detected by 16S rDNA sequencing technology. The antibiotic experiment was used to explore the role of gut microbiota in SLBZS treatment. RESULTS: The results showed that SLBZS significantly improved the physiological indexes including body weight, DAI score, and colon length of colitis mice. We focused on the effects of SLBZS on intestinal homeostasis in colitis mice. First, SLBZS could enhance the secretion of intestinal mucin and the expression levels of tight junctions and adhesive junctions. Second, SLBZS inhibited the expression level of inflammatory factors and reduced the protein expression level of NLRP3 inflammasome. Third, 16S rDNA sequencing analysis revealed that SLBZS repaired the dysfunctional gut microbiota of colitis mice, such as enhancing the abundance of short-chain fatty acid-producing bacteria including Faecalibaculum, Colidextribacter, and Coprococcus. Further, by gut microbiota-depleted mice, we found that SLBZS could not exert an anti-colitis effect when gut microbiota was absent. CONCLUSIONS: SLBZS restored intestinal environmental homeostasis by enhancing intestinal barrier function, inhibiting NLRP3 inflammasome, and restoring disturbed gut microbiota. And SLBZS could not ameliorate colitis mice with depleted gut microbiota. Our finding provided a theoretical basis for the clinical application of SLBZS in IBD.

Xihuang pill ameliorates colitis in mice by improving mucosal barrier injury and inhibiting inflammatory cell filtration through network regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of colitis is on the rise, and effective treatment options are currently lacking. Xihuang pill (XHP) is a traditional Chinese medicine formula mentioned in the "Volume 4 of Surgical Evidence and Treatment of the Whole Life" authored by the renowned doctor Hong-Xu Wang during the Qing Dynasty. It is now part of the "Volume 9 of Chinese medicine formula preparation in Drug Standard." XHP and its primary ingredients have been demonstrated anti-inflammatory properties against colitis. However, the specific effects and underlying mechanisms of XHP in treating colitis remain unknown. AIM OF THE STUDY: This study aimed to investigate the potential impact of XHP on colitis and uncover the underlying mechanisms involved. MATERIALS AND METHODS: An acute colitis model was developed in C57BL/6N mice, and the effects on weight loss, colon length, the permeability of the colonic mucosa barrier, Claudin-5 and Occludin expression, number of both infiltrating MPO-positive cells and CD68-positive cells, and the content of pro-inflammatory cytokines (IL-6, IL-22, IL-1ß, and TNF-α) in the colon tissue were investigated. Low-, medium-, and high-dose XHP (0.45, 0.9, and 1.8 g/kg/day) (batch number: z21021222) were administered to the mice by gavage over the course of two weeks. Additionally, the protein expression levels in colon tissue from the control group, colitis group, and XHP low-dose administration group mice were analyzed by quantitative proteomics techniques. The comprehensive profiling and characterization of absorbed components in mice blood following oral administration of XHP were identified by HPLC/Q-TOF-MS techniques, and the absorbed components in blood were combined with proteomics to reveal the mechanism of enteritis inhibition by XHP. RESULTS: Our findings indicated that XHP enhanced weight loss and colonic shortening of colitis mice. Additionally, XHP reduced the increase in permeability of the colonic mucosa barrier and decreased expression of Claudin-5 and Occludin, while significantly reducing the number of infiltrating MPO-positive cells and CD68-positive cells in the colon tissue. We found that XHP reduced the production of pro-inflammatory cytokines, including IL-6, IL-22, IL-1ß, and TNF-α in colon tissue. Pharmacokinetic analysis suggested that XHP contained 24 blood-entering prototype ingredients, which improved colitis through the regulation of various proteins (e.g., Ctsb, Sting1, and Abat) linked to mucosal barrier injury and inflammation. CONCLUSION: XHP improved intestinal mucosal barrier injury and reduced MPO-positive cells and CD68-positive cell infiltration through multiple targets and pathways, providing support for XHP as a promising therapy for colitis.

Indocyanin Green Fluorescence Evaluation of Colonic Perfusion During Elective Open Abdominal Aortic Aneurysm Repair.

OBJECTIVES: Colonic ischaemia is a rare but devastating complication of open aortic aneurysm repair and is associated with high morbidity and a mortality of up to 50%. The aim of this study was to determine the safety and effectiveness of using indocyanin green florescence (ICG) to interrogate colonic perfusion intra-operatively. DESIGN: Prospective observational study. METHODS: All elective open abdominal aneurysm repairs over a 6 month period underwent colonic perfusion interrogation with ICG according to a pre-defined protocol. Patient demographics and imaging findings were recorded prior to surgery. ICG was given just prior to laparotomy closure. Time to florescence was measured from the start of IV administration to surgeon defined maximal florescence of the sigmoid colon. RESULTS: Ten patients fulfilled the inclusion criteria. All patients were male with an average age of 69.7 years. Inferior mesenteric artery reimplantation was performed in 5 patients. Median colonic fluorescence time was 58 s. No complications related to ICG were identified. A single patient had clinical concern of colonic ischaemia and delayed perfusion (>3 min) on ICG; colorectal opinion advised not for immediate resection. At relook laparotomy, ischaemic colon at the area of demarcation was noted and a Hartmann's procedure was performed. No other patients had delayed perfusion and no further episodes of colonic ischaemia were noted. IMA reimplantation did not show statistical difference in colonic ICG time (P = .81, 95% CI -1.98 to 2.45). There was no statistical difference between operating times between the cohort and all repairs performed 6 months before the data collection (P = .59, 95% CI -.73 to 1.24). CONCLUSION: In this pilot study ICG appears to be a safe and useful adjunct in objective assessment of colonic perfusion during open AAA repair. Further research is required to fully determine its role in this cohort of patients.

Huanglian Ganjiang decoction alleviates ulcerative colitis by restoring gut barrier via APOC1-JNK/P38 MAPK signal pathway based on proteomic analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a kind of chronic intestinal inflammation accompanied with abdominal pain, diarrhea and hematochezia. Huanglian Ganjiang decoction (HGD) derived from "Beiji Qianjin Yao Fang" was used for UC patients clinically. However, the specific mechanism of HGD in treating UC remain unclear. AIM OF STUDY: Our study devoted to demonstrating the therapeutic effect of HGD for colitis and clarifying the underlying mechanism. MATERIALS AND METHODS: UPLC-MS was carried out to identify the ingredients of HGD. UC mice were induced by giving 3% dextran sulfate sodium (DSS) solution for one week and treated by HGD for another week. Body weight fluctuation, disease activity index (DAI), colon length and pathological change of colon tissues were observed to evaluate therapeutical effect of HGD. ELISA and qPCR were carried out to estimate the inflammatory state. Western blot, qPCR and immunofluorescence were used to access the expression of tight junction proteins. Tandem mass tag (TMT)-Based proteomics and network pharmacology was launched to screen and predict the potential targets and pathway regulated by HGD. RESULTS: Based on the UPLC-MS/MS analysis, 100 components were identified in HGD. After 7-day treatment, HGD significantly alleviated colitis-associated symptoms including body weight loss, shorted colon, increase of DAI score, histopathologic lesions. HGD also reduced inflammatory cytokines IL-6 and IL-1ß levels, increased the number of goblet cells and restored tight junction proteins Occludin, Claudin-1 in colon. Network pharmacology study predicted that tight junction and MAPK pathway might be affected by HGD in colitis mice. APOC1 was screened out as key target in HGD-treated mice using TMT-based proteomics study. Further Western blot results showed that HGD reduced expressions of APOC1, p-P38 and p-JNK. CONCLUSION: HGD improves general symptoms of colitis mice at medium and high doses, which may be associated with restoring tight junction and intestinal barrier integrity and function through suppression of APOC1-JNK/P38 MAPK signal pathway.

Main active components of Ilex rotunda Thunb. protect against ulcerative colitis by restoring the intestinal mucosal barrier and modulating the cytokine-cytokine interaction pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Ilex rotunda Thunb. (IR) is widely used for gastrointestinal diseases by Yao physician, and it has a better clinical curative effect on ulcerative colitis (UC). However, the main active components and mechanism of IR in the treatment of UC remain to be clarified. AIM OF THE STUDY: To investigate the main active components and mechanism of IR in the treatment of UC. MATERIALS AND METHODS: Ten biological active components of IR were quantified by UPLC-MS/MS. In vitro, Caco2 cell monolayers were stimulated by lipopolysaccharide, and were treated with 10 biologically active components individually to investigate the protective role of the components of IR in mucosal barrier damage. In vivo, a mouse model of UC was induced by dextran sulfate sodium and administered with the candidate active components of IR. On day 8, the serum and colon tissue were collected for histological and molecular analysis to investigate the main active components and mechanism of IR. RESULTS: Ziyuglycoside I, ziyuglycoside II, syringin, and pedunculoside in IR reduced phenol red transmission of the monolayer, and inhibited the protein expression of oncostatin M and oncostatin M receptor in Caco2 cells. Notably, ziyuglycoside II and syringin decreased the transepithelial electrical resistance of the monolayer, and promoted the protein expression of Occludin, Claudin-1 and zonula occludens-1 (ZO-1) in Caco2 cells. In vivo, ziyuglycoside II and syringin improved the symptoms of UC mice, including body weight, disease activity score, shortening of colon length, damaging of acidic mucus layer, histopathological changes, and protein expression of Occludin, Claudin-1, and ZO-1. Pedunculoside reduced the neutrophils and inflammatory response in the UC mice. Moreover, when the combination of ziyuglycoside II, syringin and pedunculoside was used for the treatment of UC, syringin and pedunculoside enhanced the therapeutic effect of ziyuglycoside II. Finally, RNA sequencing and RT-qPCR analysis revealed that ziyuglycoside II + syringin + pedunculoside and IR coregulated up to 42.7% of genes, and mainly reduced the overexpression of C-X-C motif ligand 1(CXCL1), oncostatin M receptor (OSMR), interleukin 1 receptor type I (IL1R1), tumor necrosis factor receptor superfamily member 9 (TNFRSF9), C-X-C motif chemokine 13 (CXCL13), oncostatin M (OSM), and interleukin 6 (IL-6) in the cytokine-cytokine interaction pathways. CONCLUSIONS: The combination of ziyuglycoside II, syringin, and pedunculoside protects against UC by modulating the intestinal mucosal barrier and inhibiting the cytokine-cytokine interaction pathways, and the effect is relatively equivalent to that of the water extract of Ilex rotunda Thunb.

Moluodan promotes DSS-induced intestinal inflammation involving the reprogram of macrophage function and polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: Moluodan (MLD) is a traditional Chinese medicine that is composed of 18 herbal medicines based on traditional Chinese medicine theory and practice. It has long been used in treating chronic gastritis and its components were traditionally used in dealing with intestinal inflammation. However, its specific pharmacological mechanism is still unclear. AIM OF THE STUDY: The upper and lower digestive tract diseases are correlated. In clinical practice, some chronic gastritis patients are also accompanied by intestinal inflammation. Due to the unclear pharmacological mechanism of MLD and its effect on intestinal inflammation, there is doubt whether MLD is still suitable for this type of patient. Therefore, this study aims to elucidate the pharmacological mechanism of MLD and identify its effect in the mouse model of intestinal inflammation. MATERIALS AND METHODS: Mice intestinal inflammation model was induced by 2.5% dextran sulfate sodium (DSS). The mice were given different concentrations of MLD via oral gavage (0.25, 0.5 g/kg b.w.). Pharmacodynamic indicators were assessed including body weight, colon length, disease activity index (DAI), bloody stool score, inflammatory factors, histological change, etc. RAW264.7 macrophage cells were used for in vitro experiments that illuminated the role of MLD in reprogramming macrophage function and polarization. RT-qPCR and western blots were performed to measure the mRNA and protein levels of macrophage polarization marker and effector molecules. The functions of polarized macrophages were tested using ROS detection probes, Edu assay and wound healing assay. RESULTS: The administration of MLD exhibited obvious hemostatic effects, while unexpectedly accentuating various aspects of the DSS-induced intestinal inflammation in mice, including increased body weight loss and colon shortening, elevated disease activity index, and intensified colonic tissue damage. Additionally, MLD treatment induced more severe inflammatory cell infiltration and higher proinflammatory cytokines expression in colon tissue. Further results showed that MLD promoted M1 macrophage polarization and stimulated its proinflammatory cytokines expression, while only slightly affecting the function of M2 macrophage. Western blot analysis revealed that MLD induced the phosphorylation of AKT and NF-κB. The polarization of M1 macrophages induced by MLD was inhibited by either an Akt inhibitor or a NF-κB inhibitor. CONCLUSIONS: Although MLD has an obvious hemostatic effect, it generally promoted the severity of DSS-induced colitis in mice by facilitating macrophage polarization toward the M1 phenotype through the AKT/NF-κB pathway. Our study suggested that MLD may not be suitable for colitis, especially during the acute inflammation stage.

Bioavailability and daily requirement of vitamin B12 in adult humans: an observational study of its colonic absorption and daily excretion as measured by [13C]-cyanocobalamin kinetics.

BACKGROUND: Clinical and biochemical vitamin B12 (B12) deficiency is lower than anticipated in vegetarians. Extraileal absorption, such as from the colon, as well as reduced daily excretion, may be adaptive mechanisms to maintain B12 homeostasis with marginal intakes. OBJECTIVE: To measure the absorption of B12 from the small and large intestine, and its daily rate of excretion from the body, using a [13C]-cyanocobalamin tracer. METHODS: Oral B12 bioavailability was measured over 12 h after administration of [13C]-cyanocobalamin tracer (2.5 µg) in normal participants. The colonic B12 bioavailability was evaluated by direct instillation of [13C]-cyanocobalamin (5 µg) into the ascending colon. Bioavailability was calculated from 2-compartmental modeling of the tracer appearance in plasma. The excretion rate of B12 was measured from [13C]-cyanocobalamin elimination from the body over 4 wk after oral dosing (5 µg). RESULTS: The oral B12 bioavailability (n = 11) was 63% ± 10% measured over 12 h. A late absorption peak, accounting for 12% of the absorption, was observed after an average lag time of 8.7 h from dosing. The colonic B12 bioavailability (n = 10) was 7% ± 5% over 4 h. The daily B12 excretion rate (n = 4) was 0.7 ± 0.2 µg/d. The minimum daily requirement of B12 in these participants was derived at 1 µg /d. CONCLUSIONS: B12 is absorbed in the human colon. This observation confirms the potential contribution of the colon in daily B12 nutriture, and along with a possible lower requirement, could explain the absence of clinical deficiency in populations with marginal B12 intakes. TRIAL REGISTRATION NUMBER: This study was registered in Clinical Trials Registry of India (CTRI) with the registration number CTRI/2018/04/012957, available from https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49319&EncHid=&userName=029108.

Hetong decoction relieves loperamide-induced constipation in rats by regulating expression of aquaporins.

OBJECTIVE: To investigate whether Hetong decoction (, HTT) alleviates constipation via regulating AQPs expression. METHODS: Constipation in rats was induced by loperamide, and rats were randomly assigned into model (saline), HHT-low (95 g/kg), HTT-medium (190 g/kg), HTT-high (380 g/kg) and positive control (mosapride) groups. Then the defecation function, the concentration of serum arginine vasopressin (AVP) and cyclic adenosine monophosphate (cAMP), and the expression of AQP3 and AQP8 in colon tissues were assessed. NCM460 colon cells with AQP3 and AQP8 knockdown or overexpression were exposed to serum from rats that received low or high dose of HTT, followed by detection of AQP3 and AQP8 expression. RESULTS: The model group showed lower fecal weight and water content, weaker intestinal transit, higher serum concentration of AVP and cAMP, increased proximal and distal AQP8 expression, increased proximal but decreased distal AQP3 expression. However, these trends were reversed in both the HTT group (low, medium and high dose) and the positive control group. In NCM460 cells, HTT dose-dependently stabilized AQP3 and AQP8 expression under AQP3/8 plasmid interference or overexpression. CONCLUSIONS: HTT relieves constipation in rats through regulating AQP3 and AQP8 expression.

Effect of minocycline, methyl prednisolone, or combination treatment on the colonic bacterial population in a state of colonic inflammation using the murine dextran sulfate sodium model.

BACKGROUND: Several reports demonstrated anti-inflammatory properties of minocycline in various inflammatory disorders including colitis. We have experimental evidence suggesting synergistic anti-inflammatory effect of minocycline with methyl prednisolone in reducing colitis severity in mice, but if this effect is in part related to modulating the composition of colonic microbiota is still unknown. METHODS: the effect of vehicle (V), minocycline (M), methyl prednisolone (MP), or combination (C) regimen on the composition of the microbiota of mice in a state of colon inflammation compared to untreated (UT) healthy mice was determined using 16s metagenomic sequencing, and the taxonomic and functional profiles were summarized. RESULTS: Overall, the bacterial flora from the phylum Firmicutes followed by Bacteroidota were found to be predominant in all the samples. However, the composition of Firmicutes was decreased relatively in all the treatment groups compared to UT group. A relatively higher percentage of Actinobacteriota was observed in the samples from the C group. At the genus level, Muribaculaceae, Bacteroides, Bifidobacterium, and Lactobacillus were found to be predominant in the samples treated with both drugs (C). Whereas "Lachnospiraceae NK4A136 group" and Helicobacter in the M group, and Helicobacter in the MP group were found to be predominant. But, in the UT group, Weissella and Staphylococcus were found to be predominant. Eubacterium siraeum group, Clostridia vadinBB60 group, Erysipelatoclostridium and Anaeroplasma genera were identified to have a significant (FDR p < 0.05) differential abundance in V compared to C and UT groups. While at the species level, the abundance of Helicobacter mastomyrinus, Massiliomicrobiota timonensis and uncultured Anaeroplasma were identified as significantly low in UT, C, and M compared to V group. Functional categories related to amino acid, carbohydrate, and energy metabolism, cell motility and cell cycle control were dominated overall across all the samples. Methane metabolism was identified as an enriched pathway. For the C group, "Colitis (decrease)" was among the significant (p = 1.81E-6) associations based on the host-intrinsic taxon set. CONCLUSION: Combination regimen of minocycline plus methyl prednisolone produces a synergistic anti-inflammatory effect which is part related to alternation in the colonic microbiota composition.

In vitro antibacterial effects of Broussonetia papyrifera leaf extract and its anti-colitis in DSS-treated mice.

Recently, the hybrid Broussonetia papyrifera (BP) has been extensively cultivated and predominantly utilized in ruminants because of its high protein and bioactive compound content. In the present study, the effects of an ethanolic extract of BP leaves (BPE, 200 mg/kg) on mitigating 2% dextran sodium sulfate (DSS)-induced intestinal inflammation in mice were evaluated. BPE is rich in flavonoids, polyphenols, and polysaccharides, and displays potent antioxidant and antibacterial activities against pathogenic strains such as Clostridium perfringens, Salmonella Typhimurium, and Salmonella enterica subsp. enterica in vitro. In a mouse study, oral administration of DSS resulted in weight loss, incidence of diarrhea, enlargement of the liver and spleen, impaired colonic morphology, downregulation of both gene and protein expression related to intestinal antioxidant (Nrf2) and barrier function (ZO-1), decreased diversity of colonic microbiota, and 218 differentially altered colonic metabolites; however, co-treatment with BPE did not restore these modified aspects except for the liver index and colonic bacterial diversity. The singular treatment with BPE did not manifest evident side effects in normal mice but induced a mild occurrence of diarrhea and a notable alteration in the colonic metabolite profile. Moreover, a single BPE administration augmented the abundance of the commensal beneficial bacteria Faecalibaculum and Akkermansia genera. Overall, the extract of BP leaves did not demonstrate the anticipated effectiveness in alleviating DSS-induced intestinal inflammation.

Colonic macrophages eat and feed.

Macrophages not only secure host defense via phagocytosis but also play a key role in tissue homeostasis. A comprehensive study by Fritsch et al. reveals a novel mechanism by which macrophages in the colon deliver polyamines to epithelial cells to support self-renewal of the epithelium during periods of high proliferation.

[Usefulness and safety of observing anorectal lesions by colon capsule endoscopy].

We investigated the findings of rectoanal lesions in 190 patients who underwent colon capsule endoscopy (CCE) at our hospital. Internal hemorrhoids were observed in 70 (36.8%) patients and rectal polyps in 19 (10%) patients. When conventional endoscopy (colonoscopy and double balloon endoscopy) was considered the gold standard, the sensitivity and specificity of rectal polyps were 75% and 93.4%, respectively, and those of internal hemorrhoids were 88.9% and 92.7%, respectively. The prevalence of constipation was significantly higher in the false-negative group for internal hemorrhoids, and the colonic transit time was significantly shorter in the false-negative and false-positive groups for rectal polyps. No adverse events occurred in any of the patients. CCE might be a useful and safe examination method for rectoanal lesions.

Risk factors for ischemia/necrosis of the colonic stump after proctectomy and delayed coloanal anastomosis.

INTRODUCTION: Delayed coloanal anastomosis (DCAA) is a two-stage procedure. DCAA has been increasingly reused in recent years in the management of rectal cancer. Such increased use of DCAA has highlighted the complications associated with this procedure. We aimed to evaluate the risk and risk factors of ischemia/necrosis of the colonic stump between the two stages of DCAA. PATIENTS AND METHODS: All patients who underwent a proctectomy with a DCAA were included in this retrospective single-centre study from November 2012 to June 2022. Two groups of patients were defined: patients with a well vascularized colonic stump (well vascularized group) and those who experienced ischemia or necrosis of the colonic stump (ischemic group). The primary endpoint was the rate of ischemia or necrosis of the colonic stump and an evaluation of the associated risk factors. RESULTS: During the study period, 43 patients underwent DCAA. Amongst them, 32 (75%) had a well-vascularized colonic stump (well-vascularized group) and 11 (25%) ischemia of the colonic stump (ischemic group). Relative to patients in the well-vascularized group, those in the ischemic group were more often men (81.8% vs 40.6%, p = 0.034), had a higher BMI (29.2 kg/m2 vs 25.7 kg/m2, p = 0.03), were more frequently diabetic (63.6% vs 21.9%, p = 0.01) and more frequently had had preoperative radiotherapy (100% vs 53.1%, p = 0.008). On the preoperative CT scan, the interspinous diameter was shorter in the ischemic group (9.4 ± 1.01 cm vs 10.6 ± 1.01 cm, p = 0.001), the intertuberosity diameter was shorter (9.2 ± 1.18 cm vs 11.9 ± 1.18 cm, p < 0.0001), and the length of the anal canal was longer (31.9 ± 3 mm vs 27.4 ± 3.2 mm, p < 0.0001). CONCLUSION: This study highlights clear risk factors for ischemia/necrosis of the colonic stump after proctectomy with DCAA.