Dietary Alaska Pollock Protein Attenuates the Experimental Colitis Induced by Dextran Sulfate Sodium via Regulation of Gut Microbiota and Its Metabolites in Mice

Protein derived from fish has not only nutritional properties but also health-promoting properties. Few studies have examined the effect of dietary Alaska pollock protein (APP) on the anticolitis effect reported to be associated with metabolic syndrome (MetS). This study investigated the effect of APP intake on colitis symptoms, gut microbiota, and its metabolites in the experimental colitis mouse model induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were divided into three groups: (1) DSS-untreated mice fed an American Institute of Nutrition (AIN) 93G diet (protein source is casein), (2) DSS-treated mice fed an AIN93G diet, and (3) DSS-treated mice fed an APP diet. After the mice were fed the diets for 21 days, experimental colitis was induced by three cycles of 2% DSS administration for 5 days followed by washouts over the course of 5 days. APP-reduced body weight loss increased the disease activity index, and elevated spleen weight and alleviated colon length shortening and colonic tissue damage. Furthermore, APP altered the structure and composition of the microbiota and short-chain fatty acids in feces. Since APP intake alleviates experimental colitis induced by DSS administration through alterations in the gut microbiota and its metabolites, we deduced that APP would inhibit MetS progression via colitis suppression.

Protective effects of bioactive peptides in foxtail millet protein hydrolysates against experimental colitis in mice

It is of great significance to develop a dietary intervention strategy to prevent inflammatory bowel disease (IBD). A millet-rich diet can ameliorate IBD, but the active ingredients and mechanisms remain...

Effect of Arrabideae chica (crajiru) extract in a model of induced experimental colitis in rats

Objective: This study aimed to investigate the effect of A. chica extract on the evolution of experimental rectocolitis in rats, and the expression of the pro-inflammatory cytokines TNF-a, IL-1β and IL-6 in colonic tissue. Methods: Wistar rats weighing 275±23g were distributed into 4 groups of 6 animals each. Rectocolitis was induced in rats by rectal administration of trinitrobenzene sulfonic acid (TNBS). Seventy-two hours after TNBS injection, animals were treated daily for 6 days. Groups: 1. Normal control group without induction of rectocolitis. Received 0.9% saline injection v.o. by gavage during treatment. 2. TNBS rectocolitis group, treated with normal saline (SN) by gavage (TNBS+SN); 3. TNBS rectocolitis group treated with A. chica extract (ACE), receiving a daily dose of 300 mg of A. chica extract by gavage (TNBS+ACE);4. TNBS rectocolitis group treated with mesalazine, receiving a daily dose of 100 mg/kg of mesalazine orally (TNBS+MEZ). Macroscopic examination of the colon and dosing of TNF-α, IL-1β and IL-6 in colon tissue were performed. Results: There was a reduction in weight in animals treated only with TNBS+NS. No difference in weight was observed comparing the animals treated with ACE and MEZ. In the control group no mucosal ulcers or edema of the colon wall were observed. Several mucosal ulcers, edema and hyperemia occurred in the colon of rats in the TNBS+SN group. In two of the animals in this group there was colon perforation, tamponated by omentum. A reduction of mucosal ulcers number in the TNBS+ACE (crajiru) group was seen, compared to the TNBS+SN and TNBS+MEZ group. There was a significant reduction of TNF-α, IL-1β and IL-6 in the colon tissue of animals treated with crajiru extract, TCBS+ACE group, when compared to the control group (p<0.001), TNBS+SN group, and TNBS+MEZ groups (p<0.001). Conclusion: This is the first study to show that A. chica extract positively influences the treatment of TNBS/induced rectocolitis through its antiinflamatory activity. More comprehensive studies are needed to understand the underlying mechanisms.

Coix Seed Diet Ameliorates Immune Function Disorders in Experimental Colitis Mice

Coix seed is a functional food in the Chinese diet that possesses the ability to alleviate ulcerative colitis clinically. However, the underlying mechanisms remain ambiguous. In this study, we investigated the protective effect of the Coix seed diet on experimental colitis mice. The mice were randomly divided into four groups: control group, model group, Coix seed feed group, and positive control group. The maintenance feed of the mice was replaced with Coix seed feed 10 days before orally administering the mice 5% (w/v) dextran sulfate sodium drink. As a result, the Coix seed feed alleviated colitis symptoms, maintained the complete blood count at a normal level, reduced the pathological score, relieved inflammatory cytokine secretion, and alleviated oxidative stress. Network pharmacology analysis was used for further exploration of the targets of Coix seed feed. The results showed that T-cell regulation is one of the targets of Coix seed feed, and the analysis of the T-lymphocyte subset and innate immune cell distribution of the colon tissue supported the network pharmacology results. In conclusion, Coix seed, as a staple food, can alleviate experimental colitis, and the mechanism may be related to the immune regulation effect of Coix seeds.

Biological Distribution of Orally Administered [123I]MIBG for Estimating Gastrointestinal Tract Absorption

Gastrointestinal tract absorption of cationic anticancer drugs and medicines was estimated using whole-body imaging following oral [123I]MIBG administration. [123I]MIBG was added to cultures of human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)2B1, carnitine/organic cation transporter (OCTN)1 and OCTN2, and organic cation transporter (OCT)1, OCT2, and OCT3 with and without cimetidine (an OCTN and OCT inhibitor) and L-carnitine (an OCTN inhibitor). Biodistribution analyses and single-photon emission computed tomography (SPECT) imaging in normal and dextran sodium sulfate (DSS)-induced experimental colitis mice were conducted using [123I]MIBG with and without cimetidine. [123I]MIBG uptake was significantly higher in HEK293/OCTN1, 2, and OCT1-3 cells than in mock cells. Uptake via OCTN was inhibited by L-carnitine, whereas OCT-mediated uptake was inhibited by cimetidine. Biodistribution analyses and SPECT imaging studies showed significantly lower accumulation of [123I]MIBG in the blood, heart, liver, and bladder in DSS-induced experimental colitis mice and mice with cimetidine loading compared with normal mice, whereas significantly higher accumulation in the stomach and kidney was observed after [123I]MIBG injection. [123I]MIBG imaging after oral administration can be used to estimate gastrointestinal absorption in the small intestine via OCTN and/or OCT by measuring radioactivity in the heart, liver, and bladder.

miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1

Antimicrobial responses play an important role in maintaining intestinal heath. Recently we reported that miR-511 may regulate TLR4 responses leading to enhanced intestinal inflammation. However, the exact mechanism remained unclear. In this study we investigated the effect of miR-511 deficiency on anti-microbial responses and DSS-induced intestinal inflammation. miR-511-deficient mice were protected from DSS-induced colitis as shown by significantly lower disease activity index, weight loss and histology scores in the miR-511-deficient group. Furthermore, reduced inflammatory cytokine responses were observed in colons of miR-511 deficient mice. In vitro studies with bone marrow-derived M2 macrophages showed reduced TLR3 and TLR4 responses in miR-511-deficient macrophages compared to WT macrophages. Subsequent RNA sequencing revealed Wdfy1 as the potential miR-511 target. WDFY1 deficiency is related to impaired TLR3/TLR4 immune responses and the expression was downregulated in miR-511-deficient macrophages and colons. Together, this study shows that miR-511 is involved in the regulation of intestinal inflammation through downstream regulation of TLR3 and TLR4 responses via Wdfy1.

Morphine Exacerbates Experimental Colitis-Induced Depression of Nesting in Mice

Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are excellent analgesics, but recent clinical evidence suggests that these drugs might worsen disease severity in Crohn's disease patients, limiting their clinical utility for treating Inflammatory Bowel Disease (IBD). One indicator of change in well-being from conditions such as IBD is behavioral depression and disruption to activities of daily living. Preclinical measures of behavioral depression can provide an indicator of changes in quality of life and subsequent modification by candidate analgesics. In mice, nesting is an adaptive unconditioned behavior that is susceptible to disruption by noxious stimuli, and some types of pain related nesting depression are responsive to opioid and NSAID analgesics. Here we show that a 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) model of experimental colitis depresses nesting behavior in mice, and we evaluated effects of morphine, an opioid, and ketoprofen, a NSAID, on TNBS-induced nesting depression. In Swiss Webster mice, TNBS significantly reduced nesting that peaked on Day 3 and recovered in a time-dependent manner with complete recovery by Day 7. In the absence of colonic inflammation, daily treatment with morphine (1–10 mg/kg) did not decrease nesting except at 10mg/kg/day. However, in TNBS-treated mice 3.2 mg/kg/day morphine significantly exacerbated TNBS-induced nesting depression and delayed recovery. While 3.2 mg/kg/day morphine alone did not alter locomotor activity and TNBS-induced depression of locomotion recovered, the combination of TNBS and 3.2 mg/kg/day morphine significantly attenuated locomotion and prevented recovery. Daily treatment with 3.2 or 10 mg/kg ketoprofen in TNBS-treated mice did not prevent depression of nesting. These data suggest that opioid analgesics but not NSAIDS worsen colonic inflammation-induced behavioral depression. Furthermore, these findings highlight the importance of evaluating analgesic effects in models of colonic inflammation induced depression of behavior.