Inflammation Of Gastrointestinal Tract Research Articles

The ethanol extract of Scutellaria baicalensis Georgi attenuates complete Freund's adjuvant (CFA)-induced inflammatory pain by suppression of P2X3 receptor

Ethnopharmacological relevanceScutellaria baicalensis Georgi (SBG) is a perennial herb with anti-inflammatory, antibacterial, and antioxidant activities, which is traditionally used to treat inflammation of respiratory tract and gastrointestinal tract, abdominal cramps, bacterial and viral infections. Clinically, it is often used to treat inflammatory-related diseases. Research has shown that the ethanol extract of Scutellaria baicalensis Georgi (SGE) has anti-inflammatory effect, and its main components baicalin and baicalein have analgesic effects. However, the mechanism of SGE in relieving inflammatory pain has not been deeply studied. Aim of the studyThis study aimed to evaluate the analgesic effect of SGE on complete Freund's adjuvant (CFA)-induced inflammatory pain rats, and to investigate whether its effect on relieving inflammatory pain is associated with regulation of P2X3 receptor. Materials and methodsThe analgesic effects of SGE on CFA-induced inflammatory pain rats were evaluated by measuring mechanical pain threshold, thermal pain threshold, and motor coordination ability. The mechanisms of SGE in relieving inflammatory pain were explored by detecting inflammatory factors levels, NF-κB, COX-2 and P2X3 expression, and were further verified by addition of P2X3 receptor agonist (α, β me-ATP). ResultsOur results revealed that SGE can notably increase the mechanical pain threshold and thermal pain threshold of CFA-induced inflammatory pain rats, and markedly alleviate the pathological damage in DRG. SGE could suppress the release of inflammatory factors including IL-1β, IL-6, TNF-α and restrain the expression of NF-κB, COX-2 and P2X3. Moreover, α, β me-ATP further exacerbated the inflammatory pain of CFA-induced rats, while SGE could markedly raise the pain thresholds and relieve inflammatory pain. SGE could attenuate the pathological damage, inhibit P2X3 expression, inhibit the elevation of inflammatory factors caused by α, β me-ATP. SGE can also inhibit NF-κB and ERK1/2 activation caused by α, β me-ATP, and inhibit the mRNA expression of P2X3, COX-2, NF-κB, IL-1β, IL-6 and TNF-α in DRG of rats induced by CFA coupled with α, β me-ATP. ConclusionsIn summary, our research indicated that SGE could alleviate CFA-induced inflammatory pain by suppression of P2X3 receptor.

English

Inflammatory bowel disease (IBD) is the persistent inflammation of GIT (Gastrointestinal tract). IBD mainly divided into ulcerative colitis and Crohn’s disease while the Crohn’s disease involves the whole gastrointestinal tract while ulcerative colitis is limited to the colon. The current experimental study elucidates the antioxidative and microbial homeostatic efficacy of monolaurin, monolaurin with butyric acid and propionic acid in DSS (Dextran sulfate sodium) induced acute colitis in rat model. The results revealed that total antioxidant capacity was raised significantly (P<0.05) in all the treatment groups comparative with positive control group. While the results of total oxidative stress and relevant gene expression analysis revealed that mRNA expression of cell stress pathways such as, Traf-4, Traf-6 and MAPK-8 genes (Mitogen activated Protein Kinase) pathways and Calm-2, Gerk-2 and Pias-2 genes (Calcium signaling pathways) were significantly (P<0.05) higher expressed in the positive control group as compared to negative and all the treatment groups. While as, the total antioxidant capacity and NFR-1, Keap-1 and Nef-212 were significantly (P<0.05) down expressed in positive control group as compared to all the treatment groups. Histopathological study revealed that disruption of intestinal mucosa and immune infiltration in positive control group while, restoration and regeneration of intestinal parenchyma was observed in all the treatment groups. Overall study results concluded that monolaurin, monolaurin with butyric acid, and propionic acid can develop innovative customized remedies against DSS-induced acute colitis.

Autoantibody levels in blood of <i>H. pylori</i>-infected patients with chronic gastritis

Helicobacter pylori (H. pylori) increases the risk of diseases associated with mucous membrane inflammation of gastrointestinal tract, in particular, gastritis, stomach ulcers, and duodenal ulcers. It may also induce a chronic immune response, causing damage to the mucous membrane and development of these diseases. In addition, the role of H. pylori in the initiation of a wide range of autoimmune diseases is discussed. The aim of this study was to assess the level of autoantibodies – markers of various autoimmune diseases in the blood of H. pylori-infected patients with chronic gastritis. We used samples of whole peripheral blood from 267 primary patients with chronic gastritis in the acute stage. The presence of H. pylori in gastric juice from patients was determined using real-time PCR. The level of autoantibodies to double-stranded and single-stranded DNA, autoantibodies to thyroglobulin, thyroid peroxidase, concentration of rheumatoid factor, IgG autoantibodies to the cyclic citrullinated peptide, IgM and IgG autoantibodies to beta(2)-glycoprotein were determined by the enzyme immunoassay. The average level of rheumatoid factor in blood serum was similar for H. pylori-infected and non-infected patients, and did not exceed the normal values. The level of antibodies to cyclic citrullinated peptide, one of the sensitive markers of rheumatoid arthritis, was increased in all patients, being, however, significantly lower in H. pylori-infected patients compared with non-infected persons. Autoantibodies to thyroglobulin, thyroid peroxidase are considered classic markers of autoimmune diseases of the thyroid gland. In blood of H. pylori-infected patients we have found an increased concentration of autoantibodies to thyroglobulin and thyroid peroxidase in comparison with non-infected ones, but the average level of these antibodies did not exceed the normal range. Any differences in the levels of systemic lupus erythematosus serological markers, i.e., autoantibodies to double-stranded and single-stranded DNA, were found between H. pylori-infected and non-infected patients. The levels of thrombosis risk marker in patients with systemic lupus erythematosus (IgG and IgM autoantibodies to beta(2)-glycoprotein) were also within the normal ranges. However, in H. pylori-infected patients, it even turned out to be statistically significantly lower than in non-infected ones. Thus, no data have been obtained on increased levels of the tested markers of autoimmune pathology in blood of H. pylori-infected patients with chronic gastritis at the acute stage. However, this does not allow us to make an unambiguous conclusion that the influence of H. pylori does not affect the development of immunological changes associated with autoimmune diseases.

Biotherapy Using Probiotics as Therapeutic Agents to Restore the Gut Microbiota to Relieve Gastrointestinal Tract Inflammation, IBD, IBS and Prevent Induction of Cancer

The gut microbiota is composed of several microbial strains with diverse and variable compositions in both healthy and sick people. An undisturbed gut microbiota needs to be sustained in order to perform all physiological, metabolic, and immune functions in a normal way to prevent the development of diseases. This article has reviewed the published information on the issue of disruption of the balance of the gut microbiota. This disruption could be for many reasons, such as microbial infection in the gastrointestinal tract, food poisoning, diarrhoea, chemotherapy, malnutrition, lifestyle, and ageing. If this disruption is not restored to normal, it might cause dysbiosis. Eventually, a gut microbiota interrupted by dysbiosis might initiate several health issues, such as inflammation of the gastrointestinal tract, the induction of cancer, and the progression of a variety of diseases such as irritable bowel syndrome and inflammatory bowel disease. This review concluded that biotherapy is a natural way of using probiotic products, whether in form of food, beverages, or supplements, to restore the gut microbiota disrupted by dysbiosis. Metabolites secreted by the ingested probiotics help to relieve gastrointestinal tract inflammation and can avoid the induction of cancer.

Prolonged experimental CD4+ T-cell depletion does not cause disease progression in SIV-infected African green monkeys

CD4+ T-cell depletion is a hallmark of HIV infection, leading to impairment of cellular immunity and opportunistic infections, but its contribution to SIV/HIV-associated gut dysfunction is unknown. Chronically SIV-infected African Green Monkeys (AGMs) partially recover mucosal CD4+ T-cells, maintain gut integrity and do not progress to AIDS. Here we assess the impact of prolonged, antibody-mediated CD4 + T-cell depletion on gut integrity and natural history of SIV infection in AGMs. All circulating CD4+ T-cells and >90% of mucosal CD4+ T-cells are depleted. Plasma viral loads and cell-associated viral RNA in tissues are lower in CD4+-cell-depleted animals. CD4+-cell-depleted AGMs maintain gut integrity, control immune activation and do not progress to AIDS. We thus conclude that CD4+ T-cell depletion is not a determinant of SIV-related gut dysfunction, when gastrointestinal tract epithelial damage and inflammation are absent, suggesting that disease progression and resistance to AIDS are independent of CD4+ T-cell restoration in SIVagm-infected AGMs.

Effect of a molasses-based liquid supplement on gastrointestinal tract barrier function, inflammation, and performance of newly received feedlot cattle before and after a transport stress.

The objective of this study was to determine the effect of a dry versus a molasses-based liquid supplement on ruminal butyrate concentration, gastrointestinal tract (GIT) barrier function, inflammatory status, and performance of newly received feedlot cattle. In experiment 1, 60 mixed breed steers (234 ± 2.1 kg) were weaned, held overnight at a sale barn, then transported 14 h to Purdue University. After arrival, steers were weighed, blocked by body weight, and allotted within block to treatments (six pens per treatment and five steers per pen). Diets consisted of 45% roughage and 55% concentrate (dry matter basis). Treatments differed in the supplement source as follows: DRY: 10% dry supplement or LIQUID: 10% liquid molasses-based supplement. Feed intake, average daily gain (ADG), and gain:feed were determined for the three 21-d periods and overall. In experiment 2, 16 crossbred heifers (246 ± 7.5 kg) were used (8 heifers per treatment). Diets were the same as in experiment 1 and were fed for 60 d. On d 56 ruminal fluid samples were collected at 0, 3, 6, and 9 h after feeding. To mimic a stress event, heifers were transported for 4 h on d 61, rested overnight, and transported 12 h on d 62. Blood was collected from heifers immediately prior to transport and immediately upon their return. Gut barrier function using a Cr-EDTA marker was determined after transportation. Data were analyzed using the GLIMMIX procedure of SAS. Steers fed the liquid supplement had greater (P ≤ 0.03) ADG through d 42 and overall compared to steers fed the dry supplement. Feed intake did not differ (P = 0.25) between treatments from d 0 to d 21. However, steers fed the liquid supplement showed greater (P < 0.001) dry matter intake after d 21 and overall compared to those fed the dry supplement. Steers fed the liquid supplement tended (P < 0.09) to have reduced serum haptoglobin and lipopolysaccharide-binding protein (LBP) compared to those fed the dry supplement. Heifers fed the liquid supplement had greater (P = 0.02) Cr in urine and tended (P = 0.07) to have lower serum LBP after transport compared to those fed the dry supplement. Heifers fed the liquid supplement had 72% lower serum haptoglobin before, but only a 19% lower serum haptoglobin after transport compared to animals fed the dry supplement (treatment × time; P = 0.07). Therefore, the liquid supplement altered GIT barrier function, and improved inflammatory status, resulting in increased growth of receiving cattle.

Effect of forage types differing in undigested neutral detergent fiber concentration and forage inclusion rate on reticulo-ruminal motility and fermentation, total tract barrier function, and blood metabolites of finishing beef heifers.

This study evaluated the effects of forages (BarS vs. STR) that differ in the uNDF concentration and FI rate on ruminal fermentation, total tract barrier function, reticulo-ruminal motility, and blood metabolites of beef heifers. Six ruminally cannulated Hereford × Simmental heifers (699 ± 69.1 kg BW) were used in a 6 × 6 Latin square (26 d periods) with a 2 × 3 factorial treatment arrangement. However, 1 heifer was removed from the study after period 2 due to health problems unrelated to treatment, resulting in an incomplete 6 × 6 Latin square design. Barley grain-based diets were formulated using BarS or wheat STR to alter uNDF (7.1% vs. 8.5% DM) with FI rates of 5%, 10%, or 15% of DM. There were limited interactions between the forage type and FI. DM intake was not affected (P ≥ 0.10) by forage type or FI. Use of STR vs. BarS increased uNDF intake (P < 0.001). Increasing FI increased (P < 0.001) uNDF intake for those fed 15% forage. Ruminal pH was not affected (P ≥ 0.10) by forage type; however, cattle fed 5% FI had lesser (P = 0.017) mean ruminal pH and maximum pH (P = 0.018) than those fed 10% and 15% of forage. The total SCFA concentration was not affected by forage type (P = 0.84) but cattle fed the 5% FI rate had lesser (P < 0.001) molar proportion of acetate when compared with cattle fed 10% and 15% forage. Increasing the FI rate decreased the molar proportion of propionate (P < 0.001). Feeding STR relative to BarS decreased (P = 0.041) the reticulo-ruminal contraction duration. In contrast, cattle fed the 10% and 15% FI rates had a greater (P = 0.028) contraction frequency with lower (P = 0.048) contraction area than those fed 5% forage. Plasma glucose, serum insulin, and serum amyloid A were not affected by forage type or FI rate (P ≥ 0.10). Cattle fed 15% forage had lesser (P = 0.040) concentration of serum haptoglobin when compared with cattle fed 5% or 10% forage. In conclusion, forage type used to affect the dietary uNDF concentration, and FI rate act independently suggesting that the provision of STR to increase uNDF reduces reticulo-ruminal contraction duration and total tract permeability but may not affect ruminal pH. Increasing the FI increased dietary uNDF, stabilized ruminal pH, stimulated more frequent reticulo-ruminal contractions, and may decrease the permeability of the gastrointestinal tract and systemic inflammation.

Inflammatory bowel disease in Saudi Arabia: a review article

Inflammatory Bowel Disease (IBD) encompasses chronic intestinal disorders, like ulcerative colitis (UC) and Crohn&amp;apos;s disease, causing gastrointestinal (GI) tract inflammation. Saudi Arabia, particularly among pediatric populations, has seen an increasing prevalence of IBD. Clinical symptoms, including abdominal pain, diarrhea, weight loss, and rectal bleeding, significantly impact patients&amp;apos; lives, requiring lifelong medical care, especially for children. The study highlights the growing burden of IBD in Saudi Arabia due to insufficient epidemiological data and rising disease incidence. Early IBD diagnosis is crucial for successful management and improved outcomes. Effective treatments for mild to moderate UC, such as 5-aminosalicylic acid-based drugs like mesalazine and sulfasalazine, show promising results. However, patients may experience ongoing GI symptoms even after successful treatment, underscoring the need for comprehensive care. Frequent remissions and relapses pose a challenge, necessitating continuous monitoring and appropriate medical intervention. Untreated symptoms can negatively impact patients&amp;apos; well-being and increase healthcare expenditures. Hence, exploring better approaches for long-term symptom control and mucosal repair is essential. In severe cases, surgical interventions like total colectomy become necessary, but the focus should be on optimizing medical therapies to reduce the need for drastic measures. In conclusion, early detection, accurate diagnosis, and proper management of IBD in Saudi Arabia are vital. Collaborative efforts among healthcare professionals, researchers, and policymakers are required to gather comprehensive epidemiological data and develop targeted strategies for improving IBD care. Addressing these challenges and opportunities can enhance the quality of life for IBD patients in Saudi Arabia and potentially alleviate the burden on the healthcare system.

Acute gut inflammation reduces neural activity and spine maturity in hippocampus but not basolateral amygdala

Gastrointestinal tract (gut) inflammation increases stress and threat-coping behaviors, which are associated with altered activity in fear-related neural circuits, such as the basolateral amygdala and hippocampus. It remains to be determined whether inflammation from the gut affects neural activity by altering dendritic spines. We hypothesized that acute inflammation alters dendritic spines in a brain region-specific manner. Here we show that acute gut inflammation (colitis) evoked by dextran sodium sulfate (DSS) did not affect the overall spine density in the CA1 region of hippocampus, but increased the relative proportion of immature spines to mature spines on basal dendrites of pyramidal neurons. In contrast, in animals with colitis, no changes in spine density or composition on dendrites of pyramidal cells was observed in the basolateral amygdala. Rather, we observed decreased spine density on dendrites of stellate neurons, but not the relative proportions of mature vs immature spines. We used cFos expression evoked by the forced swim task as a measure of neural activity during stress and found no effect of DSS on the density of cFos immunoreactive neurons in basolateral amygdala. In contrast, fewer CA1 neurons expressed cFos in mice with colitis, relative to controls. Furthermore, CA1 cFos expression negatively correlated with active stress-coping in the swim task and was negatively correlated with gut inflammation. These data reveal that the effects of acute gut inflammation on synaptic remodeling depend on brain region, neuronal phenotype, and dendrite location. In the hippocampus, a shift to immature spines and hypoactivity are more strongly related to colitis-evoked behavioral changes than is remodeling in basolateral amygdala.

Nestin+ Peyer's patch resident MSCs enhance healing of inflammatory bowel disease through IL-22-mediated intestinal epithelial repair.

Inflammatory bowel disease (IBD) is a chronic condition characterized by gastrointestinal tract inflammation and still lacks satisfactory treatments. Mesenchymal stromal cells (MSCs) show promising potential for treating IBD, but their therapeutic efficacy varies depending on the tissue of origin. We aim to investigate whether intestine Peyer's patch (PP)-derived MSCs have superior immunomodulatory effects on T cells and better therapeutic effects on IBD compared with bone marrow-derived MSCs. We isolated PPs-derived Nestin+ MSCs (MSCsPP ) and bone marrow-derived Nestin+ MSCs (MSCsBM ) from Nestin-GFP transgenic mice to explore their curative effects on murine IBD model. Moreover, we tested the effects of IL-22 knockdown and IL-22 overexpression on the therapeutic efficacy of MSCsPP and MSCsBM in murine IBD, respectively. We demonstrated that Nestin+ cells derived from murine PPs exhibit MSC-like biological characteristics. Compared with MSCsBM , MSCsPP possess enhanced immunoregulatory ability to suppress T cell proliferation and inflammatory cytokine production. Moreover, we observed that MSCsPP exhibited greater therapeutic efficacy than MSCsBM in murine IBD models. Interestingly, IL-22, which was highly expressed in MSCsPP , could alleviate the severity of the intestinal inflammation, while knockdown IL-22 of MSCsPP remarkably weakened the therapeutic effects. More importantly, IL-22 overexpressing MSCsBM could significantly improve the symptoms of murine IBD models. This study systemically demonstrated that murine MSCsPP have a prominent advantage in murine IBD treatment, partly through IL-22.

Landscape of sialylation patterns identify biomarkers for diagnosis and prediction of response to anti-TNF therapy in crohn's disease.

Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), causes chronic gastrointestinal tract inflammation. Thirty percent of patients do not respond to anti-tumor necrosis factor (TNF) therapy. Sialylation is involved in the pathogenesis of IBD. We aimed to identify potential biomarkers for diagnosing CD and predicting anti-TNF medication outcomes in CD. Three potential biomarkers (SERPINB2, TFPI2, and SLC9B2) were screened using bioinformatics analysis and machine learning based on sialylation-related genes. Moreover, the combined model of SERPINB2, TFPI2, and SLC9B2 showed excellent diagnostic value in both the training and validation cohorts. Importantly, a Sial-score was constructed based on the expression of SERPINB2, TFPI2, and SLC9B2. The Sial-low group showed a lower level of immune infiltration than the Sial-high group. Anti-TNF therapy was effective for 94.4% of patients in the Sial-low group but only 15.8% in the Sial-high group. The Sial-score had an outstanding ability to predict and distinguish between responders and non-responders. Our comprehensive analysis indicates that SERPINB2, TFPI2, and SLC9B2 play essential roles in pathogenesis and anti-TNF therapy resistance in CD. Furthermore, it may provide novel concepts for customizing treatment for individual patients with CD.

A novel RIPK1 inhibitor reduces GVHD in mice via a nonimmunosuppressive mechanism that restores intestinal homeostasis

AbstractIntestinal epithelial cells (IECs) are implicated in the propagation of T-cell–mediated inflammatory diseases, including graft-versus-host disease (GVHD), but the underlying mechanism remains poorly defined. Here, we report that IECs require receptor-interacting protein kinase-3 (RIPK3) to drive both gastrointestinal (GI) tract and systemic GVHD after allogeneic hematopoietic stem cell transplantation. Selectively inhibiting RIPK3 in IECs markedly reduces GVHD in murine intestine and liver. IEC RIPK3 cooperates with RIPK1 to trigger mixed lineage kinase domain-like protein-independent production of T-cell–recruiting chemokines and major histocompatibility complex (MHC) class II molecules, which amplify and sustain alloreactive T-cell responses. Alloreactive T-cell–produced interferon gamma enhances this RIPK1/RIPK3 action in IECs through a JAK/STAT1-dependent mechanism, creating a feed-forward inflammatory cascade. RIPK1/RIPK3 forms a complex with JAK1 to promote STAT1 activation in IECs. The RIPK1/RIPK3-mediated inflammatory cascade of alloreactive T-cell responses results in intestinal tissue damage, converting the local inflammation into a systemic syndrome. Human patients with severe GVHD showed highly activated RIPK1 in the colon epithelium. Finally, we discover a selective and potent RIPK1 inhibitor (Zharp1-211) that significantly reduces JAK/STAT1-mediated expression of chemokines and MHC class II molecules in IECs, restores intestinal homeostasis, and arrests GVHD without compromising the graft-versus-leukemia (GVL) effect. Thus, targeting RIPK1/RIPK3 in IECs represents an effective nonimmunosuppressive strategy for GVHD treatment and potentially for other diseases involving GI tract inflammation.

Formulation of a thermo-sensitive hydro-gel for ulcerative colitis treatment.

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) that causes chronic intestinal inflammation in gastrointestinal (GI) tract, mainly in innermost lining of colonic mucosa. In any of the UC drug therapy regimens, maintaining remission is challenging and about 20-40% of patients don't respond to conventional UC medications, namely, amino salicylates, steroids and immunosuppressive drugs. These agents can weaken the patient's immune system thus enhancing the risk of infectious diseases. Therefore, in our exploration we probed to test marine-derived anti-inflammatory compounds as potential agents to treat UC. Fucoidan, a complex fucose-rich sulphated polysaccharide originated in edible brown algae with known anti-inflammatory properties was isolated from Turbinaria ornate. Collagen (Achillis tendon) is another agent that may provide a beneficial effect in wound healing and tissue regeneration. Collagen was also reported to possess anti-UC properties. Collagen has a limitation of being in solution form even at high concentrations. We therefore formulated fucoidan with collagen that underwent a sol-gel transition and yielded a gel like consistency in situ. This formulation showed sustained release of fucoidan for about 12 hours. The fucoidan, collagen and the fucoidan-collagen formulation were tested in the dextran sodium sulfate (DSS) induced colitis model in mice. In comparison to the vehicle treated group, fucoidan-collagen hydrogel formulation led to significant reduction in the clinical scores and rectal bleeding, which was higher than the reference standard, mesalamine and those seen with fucoidan and collagen given alone.

The impact of gastrointestinal tract infection on acquiring dengue fever virus infection and haemorrhagic fever in Jeddah City, Saudi Arabia

This study aimed to investigate the relationship between gastrointestinal tract infection and dengue hemorrhagic fever. Dengue hemorrhagic fever is a syndrome caused by the dengue virus and primarily affects children below ten years of age and is spread by the Aedes aegypti mosquito. Gastrointestinal tract infection is a bacterial and parasitic infection that leads to gastrointestinal tract inflammation which involves the small intestine and the stomach. The relationship between the two can be manifested by gastrointestinal bleeding, acute pancreatitis, and fulminant liver failure. In this research work, 600 blood and feces samples of different ages and sex (7-8 worms) were collected from Jeddah city. From the blood samples, serum was made and stored at -20°C until use. The frozen sera samples were investigated for sero-detection of DENV-NS1 antigen as a rapid, sensitive, and cost-effective test to detect asymptomatic acute DENV-infected donors and anti-DENV IgM and IgG antibodies. Feces samples were processed for the detection of parasites. The data acquired from these samples of all the 600 participants were analyzed and interpreted, followed by statistical analysis using GraphPad Prism 5.0 software. All the values were considered significant, which showeda value of less than 0.05. Results were expressed aswith the range. This article documents that gastrointestinal tract manifestations frequently occur among patients with dengue hemorrhagic fever. There are close relationships between gastrointestinal tract infection and dengue hemorrhagic fever. In current work, it was established that dengue fever leads to gastrointestinal tract bleeding in the presence of intestinal parasites. Therefore, failure to identify the patients with this infection early enough can lead to an increased morbidity and mortality rate.

The Pathogenicity and Synergistic Action of Th1 and Th17 Cells in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are characterized by chronic idiopathic inflammation of gastrointestinal tract. Although the pathogenesis of IBD remains unknown, intestinal immune dysfunction has been considered as the core pathogenesis. In the intestinal immune system, T helper 1 (Th1) and Th17 cells are indispensable for intestine homeostasis via preventing pathogenic bacteria invasion, regulating metabolism and functions of intestinal epithelial cells (IECs), and promoting IEC self-renewal. However, during the development of IBD, Th1 and Th17 cells acquire the pathogenicity and change from the maintainer of intestinal homeostasis to the destroyer of intestinal mucosa. Because of coexpressing interferon-γ and interleukin-17A, Th17 cells with pathogenicity are named as pathogenic Th17 cells. In disease states, Th1 cells impair IEC programs by inducing IEC apoptosis, recruiting immune cells, promoting adhesion molecules expression of IECs, and differentiating to epithelial cell adhesion molecule-specific interferon γ-positive Th1 cells. Pathogenic Th17 cells induce IEC injury by triggering IBD susceptibility genes expression of IECs and specifically killing IECs. In addition, Th1 and pathogenic Th17 cells could cooperate to induce colitis. The evidences from IBD patients and animal models demonstrate that synergistic action of Th1 and pathogenic Th17 cells occurs in the diseases development and aggravates the mucosal inflammation. In this review, we focused on Th1 and Th17 cell programs in homeostasis and intestine inflammation and specifically discussed the impact of Th1 and Th17 cell pathogenicity and their synergistic action on the onset and the development of IBD. We hoped to provide some clues for treating IBD.

Regulation of gut microbiota-bile acids axis by probiotics in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing inflammation of gastrointestinal tract, with steadily increased incidence and prevalence worldwide. Although the precise pathogenesis remains unclear, gut microbiota, bile acids (BAs), and aberrant immune response play essential roles in the development of IBD. Lately, gut dysbiosis including certain decreased beneficial bacteria and increased pathogens and aberrant BAs metabolism have been reported in IBD. The bacteria inhabited in human gut have critical functions in BA biotransformation. Patients with active IBD have elevated primary and conjugated BAs and decreased secondary BAs, accompanied by the impaired transformation activities (mainly deconjugation and 7α-dehydroxylation) of gut microbiota. Probiotics have exhibited certain positive effects by different mechanisms in the therapy of IBD. This review discussed the effectiveness of probiotics in certain clinical and animal model studies that might involve in gut microbiota-BAs axis. More importantly, the possible mechanisms of probiotics on regulating gut microbiota-BAs axis in IBD were elucidated, which we focused on the elevated gut bacteria containing bile salt hydrolase or BA-inducible enzymes at genus/species level that might participate in the BA biotransformation. Furthermore, beneficial effects exerted by activation of BA-activated receptors on intestinal immunity were also summarized, which might partially explain the protect effects and mechanisms of probiotics on IBD. Therefore, this review will provide new insights into a better understanding of probiotics in the therapy targeting gut microbiota-BAs axis of IBD.

Helicobacter bilis Contributes to the Occurrence of Inflammatory Bowel Disease by Inducing Host Immune Disorders

Gut microbiota coevolve with humans to achieve a symbiotic relationship, which ultimately leads to physiological homeostasis. A variety of diseases can occur once this balance is disrupted. Helicobacter bilis (H. bilis) is an opportunistic pathogen in humans, triggering multiple diseases, including inflammatory bowel disease (IBD). IBD is a chronic immunologically mediated inflammation of the human gastrointestinal tract, and its occurrence is closely related to the gut microbiota. Several studies have demonstrated that H. bilis colonization is associated with IBD, and its mechanism is related to host immunity. However, few studies have investigated these mechanisms of action. Therefore, this article is aimed at reviewing these studies and summarizing the mechanisms of H. bilis-induced IBD from two perspectives: adaptive immunity and innate immunity. Furthermore, this study provides a preliminary discussion on treating H. bilis-related IBD. In addition, we also demonstrated that H. bilis played an important role in promoting the carcinogenesis of IBD and discussed its mechanism.

Engineered Cancer Targeting Microbes and Encapsulation Devices for Human Gut Microbiome Applications.

The gut microbiota produce specialized metabolites that are important for maintaining host health homeostasis. Hence, unstable production of these metabolites can contribute to diseases such as inflammatory bowel disease and colon cancer. While fecal transplantation or dietary modification approaches can be used to correct the gut microbial community's metabolic output, this Perspective focuses on the use of engineered bacteria. We highlight recent advances in bacterial synthetic biology approaches for the treatment of colorectal cancer and systemic tumors and discuss the functionality and biochemical properties of novel containment approaches using hydrogel-based and electronic devices. Synthetic circuitry refinement and incorporation of novel functional modules have enabled more targeted detection of colonic tumors and delivery of anticancer compounds inside the gastrointestinal (GI) tract, as well as the design of tumor-homing bacteria capable of recruiting infiltrating T cells. Engineering challenges in these applications include the stability of the genetic circuits, long-term engraftment of the chosen chassis, and containment of the synthetic microbes' activity to the diseased tissues. Hydrogels are well-suited to the encapsulationo of living organisms due to their matrix structure and tunable porosity. The matrix structure allows a dried hydrogel to collect and contain GI contents. Engineered bacteria that sense GI tract inflammation or tumors and release bioactive metabolites to the targeted area can be encapsulated. Electronic devices can be enabled with additional measuring and data processing capabilities. We expect that engineered devices will become more important in the containment and delivery of synthetic microbes for diagnostic and therapeutic applications.

Visualization of Inflammation in Experimental Colitis by Magnetic Resonance Imaging Using Very Small Superparamagnetic Iron Oxide Particles.

Inflammatory bowel diseases (IBD) comprise mainly ulcerative colitis (UC) and Crohn´s disease (CD). Both forms present with a chronic inflammation of the (gastro) intestinal tract, which induces excessive changes in the composition of the associated extracellular matrix (ECM). In UC, the inflammation is limited to the colon, whereas it can occur throughout the entire gastrointestinal tract in CD. Tools for early diagnosis of IBD are still very limited and highly invasive and measures for standardized evaluation of structural changes are scarce. To investigate an efficient non-invasive way of diagnosing intestinal inflammation and early changes of the ECM, very small superparamagnetic iron oxide nanoparticles (VSOPs) in magnetic resonance imaging (MRI) were applied in two mouse models of experimental colitis: the dextran sulfate sodium (DSS)-induced colitis and the transfer model of colitis. For further validation of ECM changes and inflammation, tissue sections were analyzed by immunohistochemistry. For in depth ex-vivo investigation of VSOPs localization within the tissue, Europium-doped VSOPs served to visualize the contrast agent by imaging mass cytometry (IMC). VSOPs accumulation in the inflamed colon wall of DSS-induced colitis mice was visualized in T2* weighted MRI scans. Components of the ECM, especially the hyaluronic acid content, were found to influence VSOPs binding. Using IMC, co-localization of VSOPs with macrophages and endothelial cells in colon tissue was shown. In contrast to the DSS model, colonic inflammation could not be visualized with VSOP-enhanced MRI in transfer colitis. VSOPs present a potential contrast agent for contrast-enhanced MRI to detect intestinal inflammation in mice at an early stage and in a less invasive manner depending on hyaluronic acid content.

Effect of Calorie Restriction on Intestinal Inflammation in Mice Treated with a High-Calorie Diet

Abstract Inflammatory bowel disease (IBD) is classified into ulcerative colitis and Crohn's disease. It is chronic inflammation of gastrointestinal tract and idiopathic disease. Sugar is proved to be risk factor for IBD. Calorie restriction is a nutrition intervention to reduce energy intake and can reduce chronic desease. This study aims to determine the difference in the effect of a high-calorie diet and calorie restriction on intestinal inflammation. Eight-week-old healthy female Balb/c mice were divided into two groups. The high calorie (HC) group was fed standard diet plus oral gavage of glucose solution every day for 4 weeks. The dose of glucose solution was 0.0325 ml/gBW or 3-5% additional calories each day. The calorie restriction (CR) group had their calorie intake restricted to 50% of standard diet 3 times a week. After 4 weeks of treatment, the mice had their colon removed. The assessment of the intestinal inflammation was carried out using a light microscope, with a scoring system by Erben et al (2014) in HE staining. The mean score of the HC group was 1.22, this was higher than the CR group with a mean score of 1.18 even tough the result revealed that the scores of intestinal inflammation were not significantly different in the two groups (P = 0.827). However, there is no evidence for the underlying mechanism of intestinal inflammation by high-calorie diet and improvement of intestinal inflammation in high-calorie diet via calorie restriction. Thus, further research is needed on other calorie restriction methods in high-calorie diet study. Keywords: High calorie diet, Calorie restriction, Intestinal inflammation