RESUMO
Short-chain fatty acids (SCFAs) play a pivotal role in maintaining intestinal homeostasis. We aimed to investigate the effects of SCFA supplementation on gut inflammation and microbiota composition in a murine colitis model. Mice were fed with sodium butyrate or a mixture of SCFAs in the drinking water for 2 weeks, followed by 2% dextran sulfate sodium (DSS) for 7 d. After euthanasia, mouse colons were extracted to examine histological findings. Flow cytometry of the mouse colon tissues was performed to assess T cell differentiation. Changes in gut microbiota were assessed by high-throughput sequencing of the mouse feces. There were no significant differences in weight change, colonic length, or histologic inflammation score between the DSS, butyrate, and SCFA mix groups. However, flow cytometry revealed that both the expression of CD4+Foxp3+ regulatory T cells and of IL-17-producing T cells were increased in the butyrate and SCFA mix groups. Microbial compositions of the butyrate and SCFA mix groups were significantly different from those of the control and DSS groups in principal coordinate analysis. Relative abundances of the phyla Verrucomicrobia and Proteobacteria, species Akkermansia muciniphila and Escherichia fergusonii were increased in the butyrate and SCFA mix groups. Genera Roseburia and Lactobacillus showed a negative correlation with the degree of colitis, whereas genera Escherichia and Mucispirillum showed a positive correlation. SCFA supplementation did not result in a significant reduction in colon inflammation, but it promoted both regulatory T cell and IL-17-producing T cell expression, and increased both protective and aggressive gut microbiota.
Assuntos
Butiratos/administração & dosagem , Suplementos Nutricionais , Ácidos Graxos Voláteis/administração & dosagem , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Animais , Diferenciação Celular , Colite/imunologia , Colite/microbiologia , Colite/patologia , Colo/patologia , Modelos Animais de Doenças , Fezes/microbiologia , Feminino , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Doenças Inflamatórias Intestinais/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologiaRESUMO
Podophyllotoxin (POD), a natural lignan distributed in podophyllum species, possesses significant antitumor and antiviral activities. But POD often causes serious side effects, such as myelosuppression, gastrointestinal toxicity, neurotoxicity, hepatic and renal dysfunction, and even death, which not only hinder its clinical application but also threaten the patient's health. Therefore, an effective treatment against POD-induced toxicity is important. Our preliminary study found that the total saponins from the stems and leaves of Panax quinquefolius L. (PQS) could significantly reduce the death of mice caused by POD. To reveal how PQS can alleviate POD-induced toxicity, further study was needed. Peripheral blood cell analysis, diarrhea score, and histological examination demonstrated that PQS could relieve myelosuppression and gastrointestinal side effects induced by POD. Then, metabolomics was performed to investigate the possible protective mechanism of PQS on POD-induced myelosuppression and gastrointestinal toxicity. Metabolomics analysis showed that metabolic changes caused by POD could be reversed by PQS to some extent; 23 metabolites altered significantly after POD exposure, and 11 metabolites significantly reversed by PQS pretreatment. Metabolic pathway analysis suggested that PQS might exhibit its protective effects by rebalancing disordered arginine, glutamine, and unsaturated fatty acid metabolism.
Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Panax/química , Podofilotoxina/toxicidade , Substâncias Protetoras/farmacologia , Saponinas/farmacologia , Animais , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Cromatografia Líquida de Alta Pressão , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Masculino , Espectrometria de Massas , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos ICR , Folhas de Planta/químicaRESUMO
BACKGROUND: Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation. METHODS: Male wild-type (129 s1/SvlmJ) mice aged 8-15 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks. RESULTS: A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia. The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1ß (p = 0.09), IL-6 (p = 0.03), and TNF-α (p < 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 (p = 0.07) and TNF-α (p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring. CONCLUSIONS: Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.
Assuntos
Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação , Triglicerídeos/administração & dosagem , Animais , Bactérias/classificação , Colectomia , Doença de Crohn , Citocinas/metabolismo , Disbiose , Ácidos Graxos Voláteis , Fezes , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/patologia , Íleo , Doenças Inflamatórias Intestinais , Intestino Grosso , Intestino Delgado , Masculino , CamundongosRESUMO
There is increasing awareness that a broad range of gastrointestinal diseases, and some systemic diseases, are characterized by failure of the mucosal barrier. Bovine colostrum is a complex biological fluid replete with growth factors, nutrients, hormones, and paracrine factors which have a range of properties likely to contribute to mucosal healing in a wide range of infective, inflammatory, and injury conditions. In this review, we describe the anatomy and physiology of the intestinal barrier and how it may fail. We survey selected diseases in which disordered barrier function contributes to disease pathogenesis or progression, and review the evidence for or against efficacy of bovine colostrum in management. These disorders include enteropathy due to non-steroidal anti-inflammatory drugs (NSAIDs), inflammatory bowel disease (IBD), necrotizing enterocolitis, infectious diarrhea, intestinal failure, and damage due to cancer therapy. In animal models, bovine colostrum benefits NSAID enteropathy, IBD, and intestinal failure. In human trials, there is substantial evidence of efficacy of bovine colostrum in inflammatory bowel disease and in infectious diarrhea. Given the robust scientific rationale for using bovine colostrum as a promoter of mucosal healing, further work is needed to define its role in therapy.
Assuntos
Colostro/química , Gastroenteropatias/terapia , Trato Gastrointestinal/patologia , Animais , Bovinos , Ensaios Clínicos como Assunto , HumanosRESUMO
Pancreatic enzyme replacement therapy (PERT) and fat predigestion are key in ensuring the optimal growth of patients with cystic fibrosis. Our study attempted to highlight differences between fat predigestion and conventional PERT on body composition of young pigs with exocrine pancreatic insufficiency (EPI). EPI and healthy pigs were fed with high-fat diet for six weeks. During the last two weeks of the study, all pigs received additional nocturnal alimentation with Peptamen AF (PAF) and were divided into three groups: H-healthy pigs receiving PAF; P-EPI pigs receiving PAF+PERT; and L-EPI pigs receiving PAF predigested with an immobilized microbial lipase. Additional nocturnal alimentation increased the body weight gain of EPI pigs with better efficacy in P pigs. Humerus length and area in pigs in groups L and P were lower than that observed in pigs in group H (p value 0.005-0.088). However, bone mineral density and strength were significantly higher in P and L as compared to that of H pigs (p value 0.0026-0.0739). The gut structure was improved in P pigs. The levels of neurospecific proteins measured in the brain were mainly affected in P and less in L pigs as compared to H pigs. The beneficial effects of the nocturnal feeding with the semielemental diet in the prevention of EPI pigs' growth/development retardation are differently modified by PERT or fat predigestion in terms of growth, bone properties, neurospecific protein distribution, and gut structure.
Assuntos
Dieta , Terapia de Reposição de Enzimas , Insuficiência Pancreática Exócrina/terapia , Comportamento Alimentar , Lipase/uso terapêutico , Pancrelipase/uso terapêutico , Animais , Astrócitos/metabolismo , Composição Corporal , Osso e Ossos/patologia , Trato Gastrointestinal/patologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Suínos , Aumento de PesoRESUMO
Supplementation of cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA) with high concentration pyridoxal 5'-phosphate, the cofactor of vitamin B6, potentiates the cytotoxicity of FUra in a synergistic interaction mode. We report a pilot study in 13 patients with previously untreated advanced carcinoma of the digestive tract to assess the impact of high-dose pyridoxine (PN) on the antitumor activity of regimens comprising FUra and FA. Five patients had colorectal adenocarcinoma (CRC); 5 had pancreas adenocarcinoma (PC); and 3 had squamous cell carcinoma of the esophagus (EC). Patients with CRC and with PC received oxaliplatin, irinotecan, FUra and FA, and patients with EC had paclitaxel, carboplatin, FUra and FA. PN iv from 1000 to 3000 mg/day preceded each administration of FA and FUra. Eleven patients responded. Two patients with CRC attained CRs and 3 had PRs with reduction rates ≥ 78%. Two patients with PC attained CRs, and 2 had PRs with reduction rates ≥ 79%. Responders experienced disappearance of most metastases. Of 3 patients with EC, 2 attained CRs. Median time to attain a response was 3 months. Unexpected toxicity did not occur. Results suggest that high-dose vitamin B6 enhances antitumor potency of regimens comprising FUra and FA.
Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Complexo Vitamínico B/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Combinação de Medicamentos , Feminino , Fluoruracila/uso terapêutico , Trato Gastrointestinal/patologia , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Piridoxina/uso terapêuticoRESUMO
Exposure to gluten, a protein present in wheat rye and barley, is the major inducer for human Celiac Disease (CD), a chronic autoimmune enteropathy. CD occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen (HLA) DQ2/DQ8. Gut epithelial cell stress and the innate immune activation are responsible for the breaking oral tolerance to gliadin, a gluten component. To date, the only treatment available for CD is a long-term gluten-free diet. Several studies have shown that an altered composition of the intestinal microbiota (dysbiosis) could play a key role in the pathogenesis of CD through the modulation of intestinal permeability and the regulation of the immune system. Here, we show that gliadin induces a chronic endoplasmic reticulum (ER) stress condition in the small intestine of a gluten-sensitive mouse model and that the coadministration of probiotics efficiently attenuates both the unfolded protein response (UPR) and gut inflammation. Moreover, the composition of probiotics formulations might differ in their activity at molecular level, especially toward the three axes of the UPR. Therefore, probiotics administration might potentially represent a new valuable strategy to treat gluten-sensitive patients, such as those affected by CD.
Assuntos
Suplementos Nutricionais , Estresse do Retículo Endoplasmático , Intolerância Alimentar/terapia , Trato Gastrointestinal/patologia , Gliadina/efeitos adversos , Glutens/efeitos adversos , Inflamação/patologia , Probióticos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células CACO-2 , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Ligação ao GTP/metabolismo , Trato Gastrointestinal/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Permeabilidade , Probióticos/administração & dosagem , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases/metabolismo , Regulação para CimaRESUMO
Background: Phytoncide is known to have antimicrobial and anti-inflammatory properties. Purpose: This study was carried out to confirm the anti-inflammatory activity of two types of phytoncide extracts from pinecone waste. Methods: We made two types of animal models to evaluate the efficacy, an indomethacin-induced gastroenteritis rat model and a dextran sulfate sodium-induced colitis mouse model. Result: In the gastroenteritis experiment, the expression of induced-nitric oxide synthase (iNOS), a marker for inflammation, decreased in the phytoncide-supplemented groups, and gastric ulcer development was significantly inhibited (p < 0.05). In the colitis experiment, the shortening of the colon length and the iNOS expression were significantly suppressed in the phytoncide-supplemented group (p < 0.05). Conclusions: Through this study, we confirmed that phytoncide can directly inhibit inflammation in digestive organs. Although further research is needed, we conclude that phytoncide has potential anti-inflammatory properties in the digestive tract and can be developed as a functional agent.
Assuntos
Anti-Inflamatórios , Colite Ulcerativa/tratamento farmacológico , Trato Gastrointestinal/efeitos dos fármacos , Monoterpenos , Pinus/química , Extratos Vegetais , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Trato Gastrointestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monoterpenos/farmacologia , Monoterpenos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The accidental ingestion of the third larval stage of Anisakis can cause acute clinical symptoms, which are relieved via extraction of the larvae. Although this is a highly effective technique, it can only be practiced when the larvae are found in accessible areas of the gastrointestinal tract, and therefore instead the condition has often been treated using various different drugs. AIMS: This study evaluates the effectiveness of gastric acid secretion inhibitors (omeprazole and ranitidine), gastric mucosal protectants (sucralfate) and anthelmintics (mebendazole and flubendazole) in treating anisakiasis in Wistar rats. METHODS: Rats were infected with Anisakis-type I larvae and administered the drugs via a gastric probe. Data were recorded regarding the number of live and dead larvae, their location both within the animal and in its feces, and the presence of gastrointestinal lesions. Additionally, gastric pH was measured and histology performed. RESULTS: While rats in all experimental groups exhibited lesions; those treated with ranitidine and mebendazole showed significantly fewer lesions (50% and 35% of rats exhibited lesions, respectively). Histological examination of the gastric lesions revealed infection-induced changes, but no significant differences were observed between the treated and untreated rats. CONCLUSIONS: Mebendazole was found to be most efficacious in preventing gastrointestinal lesions, followed by ranitidine, which was the most effective antacid of those studied. Both these drugs could thus be considered as part of the conservative management of anisakiasis.
Assuntos
Anisaquíase/tratamento farmacológico , Anti-Helmínticos/uso terapêutico , Antiulcerosos/uso terapêutico , Antinematódeos/uso terapêutico , Modelos Animais de Doenças , Sucralfato/uso terapêutico , Doença Aguda , Animais , Anisaquíase/patologia , Anti-Helmínticos/farmacologia , Antiulcerosos/farmacologia , Antinematódeos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Peixes/parasitologia , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/parasitologia , Trato Gastrointestinal/patologia , Mebendazol/farmacologia , Mebendazol/uso terapêutico , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Ranitidina/farmacologia , Ranitidina/uso terapêutico , Ratos , Ratos Wistar , Sucralfato/farmacologiaRESUMO
AIMS: Many gastrointestinal (GI) disorders are developmental in origin and are caused by abnormal enteric nervous system (ENS) formation. Maternal vitamin A deficiency (VAD) during pregnancy affects multiple central nervous system developmental processes during embryogenesis and fetal life. Here, we evaluated whether maternal diet-induced VAD during pregnancy alone can cause changes in the ENS that lead to GI dysfunction in rat offspring. MAIN METHODS: Rats were selected to construct animal models of normal VA, VA deficiency and VA supplementation. The fecal water content, total gastrointestinal transmission time and colonic motility were measured to evaluate gastrointestinal function of eight-week-old offspring rats. The expression levels of RARß, SOX10, cholinergic (ChAT) and nitrergic (nNOS) enteric neurons in colon tissues were detected through western blot and immunofluorescence. Primary enteric neurospheres were treated with retinoic acid (RA), infection with Ad-RARß and siRARß adenovirus, respectively. KEY FINDINGS: Our data revealed marked reductions in the mean densities of cholinergic and nitrergic enteric neurons in the colon and GI dysfunction evidenced by mild intestinal flatulence, increased fecal water content, prolonged total GI transit time and reduced colon motility in adult offspring of the VAD group. Interestingly, maternal VA supplementation (VAS) during pregnancy rescued these changes. In addition, in vitro experiments demonstrated that exposure to appropriate doses of RA promoted enteric neurosphere differentiation into cholinergic and nitrergic neurons, possibly by upregulating RARß expression, leading to enhanced SOX10 expression. SIGNIFICANCE: Maternal VAD during pregnancy is an environmental risk factor for GI dysfunction in rat offspring.
Assuntos
Neurônios Colinérgicos/metabolismo , Gastroenteropatias/metabolismo , Trato Gastrointestinal/metabolismo , Neurônios Nitrérgicos/metabolismo , Receptores do Ácido Retinoico/biossíntese , Deficiência de Vitamina A/sangue , Animais , Células Cultivadas , Neurônios Colinérgicos/patologia , Feminino , Gastroenteropatias/patologia , Trato Gastrointestinal/patologia , Neurônios Nitrérgicos/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley , Receptores do Ácido Retinoico/antagonistas & inibidores , Deficiência de Vitamina A/complicaçõesRESUMO
Gut barrier dysfunction promotes chronic inflammation, contributing to several gastrointestinal diseases, including colorectal cancer. Preliminary evidence suggests that vitamin D and calcium could prevent colorectal carcinogenesis, in part, by influencing gut barrier function. However, relevant human data are scarce. We tested the effects of supplemental calcium (1,200 mg/day) and/or vitamin D3 (1,000 IU/day) on circulating concentrations of biomarkers of gut permeability (anti-flagellin and anti-lipopolysaccharide IgA and IgG, measured via ELISA) from baseline to 1 and 3 or 5 years postbaseline among 175 patients with colorectal adenoma in a randomized, double-blinded, placebo-controlled clinical trial. We also assessed factors associated with baseline concentrations of these biomarkers. We found no appreciable effects of supplemental vitamin D3 and/or calcium on individual or aggregate biomarkers of gut permeability. At baseline, a combined permeability score (the summed concentrations of all four biomarkers) was 14% lower among women (P = 0.01) and 10% higher among those who consumed >1 serving per day of red or processed meats relative to those who consumed none (P trend = 0.03). The permeability score was estimated to be 49% higher among participants with a body mass index (BMI) > 35 kg/m2 relative to those with a BMI < 22.5 kg/m2 (P trend = 0.17). Our results suggest that daily supplemental vitamin D3 and/or calcium may not modify circulating concentrations of gut permeability biomarkers within 1 or 3-5 years, but support continued investigation of modifiable factors, such as diet and excess adiposity, that could affect gut permeability. PREVENTION RELEVANCE: Calcium and vitamin D may be involved in regulating and maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which results in exposure of the host to luminal bacteria, endotoxins, and antigens leading to potentially cancer-promoting endotoxemia and chronic colon inflammation. While our results suggest that daily supplementation with these chemopreventive agents does not modify circulating concentrations of gut permeability biomarkers, they support continued investigation of other potential modifiable factors, such as diet and excess adiposity, that could alter gut barrier function, to inform the development of treatable biomarkers of risk for colorectal neoplasms and effective colon cancer preventive strategies.
Assuntos
Adenoma/tratamento farmacológico , Biomarcadores Tumorais/sangue , Cálcio da Dieta/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Suplementos Nutricionais , Trato Gastrointestinal/efeitos dos fármacos , Vitamina D/administração & dosagem , Adenoma/metabolismo , Adenoma/patologia , Idoso , Cálcio da Dieta/sangue , Estudos de Casos e Controles , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Método Duplo-Cego , Feminino , Seguimentos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Permeabilidade , Prognóstico , Vitamina D/sangue , Vitaminas/administração & dosagem , Vitaminas/sangueRESUMO
In this study, the crude exopolysaccharides (CEPSs) from fungus Aspergillus cristatus (MK346334, NCBI) isolated from Fuzhuan brick tea and its main purified fraction (EPSs-2) were investigated. Using the RAW264.7 cell model, EPSs-2 exhibited an excellent immunomodulatory effect in vitro. Then, the regulating effects of EPSs on immune function and gut microbiota were evaluated using a cyclophosphamide (Cy)-induced mice model. It was found that both CEPSs and EPSs-2 improved the body weight loss, immune organ indexes as well as the levels of TNF-α, IL-1ß, IFN-γ and IgA, exhibiting potent immunoregulatory activity. Moreover, CEPSs and EPSs-2 not only attenuated the intestinal tissue damage, but also promoted the production of short-chain fatty acids and modulated the microbial composition by increasing the growth of Muribaculaceae, Prevotellaceae_UCG-001, Bacteroides, Parabacteroides and Tidjanibacter, while decreasing the relative abundances of Helicobacter, Bilophila, Mucispirillum, Lachnospiraceae, Ruminococcaceae and Clostridiales. These results indicated that the EPSs, especially EPSs-2, exhibited immunomodulatory activity associated with the modulation of gut microbiota to maintain gut homeostasis, which provided evidence for the development of novel potential prebiotics and immunomodulators.
Assuntos
Aspergillus/metabolismo , Citocinas/metabolismo , Fungos/isolamento & purificação , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Homeostase , Chá/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Peso Corporal , Sobrevivência Celular , Colo/patologia , Ciclofosfamida , Ácidos Graxos Voláteis , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Trato Gastrointestinal/patologia , Jejuno/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7RESUMO
Antibiotic-associated diarrhea (AAD) is typically mediated by antibiotic therapy, which has increased in prevalence in recent years. Previous studies have suggested that ginger, a common spice and herbal medicine, can modulate the composition of gut microbiota and is beneficial against gastrointestinal disease. This study investigates the therapeutic effects of fresh ginger extract on AAD in a rat model. Gut microbiota and intestinal barrier function were also studied. Ginger was administered to rats with AAD. Diarrhea symptoms were assessed, and 16s rRNA sequencing analysis of gut microbiota was performed. An AAD model was successfully established, and ginger was found to effectively ameliorate AAD-related diarrhea symptoms. After the intervention of ginger decoction, the diversity (rather than richness) of gut microbiota was significantly improved, and the gut microbiota recovery was accelerated. At the genus level, Escherichia_Shigella and Bacteroides levels decreased and increased the most, respectively. Additionally, these changes were demonstrated to be coincidental with the moderate restoration of intestinal barrier function, especially the restoration of tight junction protein ZO-1. Our data indicate that ginger could restore gut microbiota and intestinal barrier function during alleviation of AAD.
Assuntos
Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Extratos Vegetais/farmacologia , Zingiber officinale/química , Animais , Bactérias/classificação , Bactérias/genética , Colo/patologia , Defecação , Diarreia , Trato Gastrointestinal/patologia , Masculino , RNA Ribossômico 16S , Ratos , Ratos Sprague-Dawley , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
OBJECTIVES: Xiao-Ban-Xia-Tang decoction (XBXT), an antiemetic formula in traditional Chinese medicine, has been proved to be a potential treatment for chemotherapy-induced nausea and vomiting (CINV), but the underlying mechanisms are not adequately understood. This study aimed to investigate changes in the ileum transcriptome after cisplatin and XBXT treatment and to reveal whether the antiemetic mechanisms of XBXT are related to its anti-inflammatory effect. METHODS: The pica model was established by a single intraperitoneal injection of 6 mg/kg cisplatin in Wistar rats. Tissues from the gastric antrum and ileum were stained with hematoxylin-eosin to observe gastrointestinal tract pathological changes. Based on the differentially expressed genes (DEGs) which were altered by cisplatin and reversed by XBXT, the transcriptome data of rat ileum were analyzed by GO, KEGG, and PPI analyses. Several inflammatory DEGs were validated by RT-PCR. RESULTS: XBXT could reduce kaolin intake up to 72 h after modeling and alleviate the inflammatory damage of gastric antrum and ileum induced by cisplatin. According to the transcriptome profile, there were 75 DEGs down-regulated by cisplatin and up-regulated by XBXT and 343 DEGs up-regulated by cisplatin and down-regulated by XBXT. XBXT could blunt the overexpression of tryptophan hydroxylase 1 (the rate-limiting enzyme of serotonin synthesis) in ileum. Enrichment analysis showed that inhibiting overexpression of several conventional inflammation pathways and pro-inflammation cytokines were related to the antiemetic effectiveness of XBXT. CONCLUSIONS: This study implies that inhibiting inflammatory signaling pathways and synthesis of serotonin might be potential mechanisms of XBXT's antiemetic effect against CINV.
Assuntos
Anti-Inflamatórios/farmacologia , Antieméticos/farmacologia , Cisplatino/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , RNA-Seq , Animais , Citocinas/análise , Modelos Animais de Doenças , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Masculino , Pica/induzido quimicamente , Pica/tratamento farmacológico , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Triptofano Hidroxilase/antagonistas & inibidoresRESUMO
Background Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves' disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients. Methods Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice. Results There were significant differences in α and ß diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients' gut was significantly decreased, which resulted in the increased serum lipopolysaccharide (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels. Conclusions Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.
Assuntos
Disbiose/complicações , Microbioma Gastrointestinal , Trato Gastrointestinal/patologia , Hipotireoidismo/complicações , Glândula Tireoide/patologia , Adulto , Animais , Estudos de Casos e Controles , Ácidos Graxos/metabolismo , Transplante de Microbiota Fecal , Feminino , Humanos , Masculino , Metagenômica , Camundongos Endogâmicos BALB C , Filogenia , Curva ROCRESUMO
PURPOSE OF REVIEW: The world is experiencing the evolving situation associated with the outbreak of the Corona Virus Disease-2019 (COVID-19) virus, and there is more of need than ever for stress management and self-care. In this article, we will define the physiological, psychological and social aspects, stages, and components of stress reactions in the context of COVID-19, review the relevant literature on stress reactions, and offer some guidance on how to help patients mitigate the physiological and psychological impact of the pandemic through resilience-building techniques. RECENT FINDINGS: There is continued evidence that the fight or flight response involves activation throughout the body at physiological, biochemical and immune levels. This response can be mitigated through increasing parasympathetic nervous system activation as well as cognitive and behavioral interventions. SUMMARY: This article will review the stress, provide a theoretical layout to predict upcoming response, and offer clinicians some practical interventions to employ as the stress of the COVID-19 pandemic continues.
Assuntos
Infecções por Coronavirus/psicologia , Pneumonia Viral/psicologia , Resiliência Psicológica , Estresse Psicológico/terapia , COVID-19 , Infecções por Coronavirus/epidemiologia , Gastroenteropatias/prevenção & controle , Gastroenteropatias/psicologia , Trato Gastrointestinal/patologia , Humanos , Sistemas Neurossecretores/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Terapia de Relaxamento , Autocuidado , Estresse Fisiológico , Estresse Psicológico/fisiopatologiaRESUMO
A 14-day experiment was conducted to explore the pathological process and immune response of soybean meal (SBM) induced enteritis (SBMIE) in grass carp (Ctenopharyngodon idellus). The complete replacement of dietary fish meal (FM) with SBM resulted in a remarkable reduction in final body weight, weight gain ratio, and feed conversion efficiency (p < 0.05). The typical histopathological changes of SBMIE appeared starting at day 4, and progressively increased in severity until day 8, then gradually subsided after day 11. The course of SBMIE could be divided into incubation period (days 1-2), prodromal period (days 3-6), symptomatic period (days 7-10), and convalescent period (days 11-14). Transcription levels of pro-inflammatory cytokines, including IL-1ß, TNF-α, IL-6, IL-8, IL-17A/F1 and IFN-γ2, were up-regulated during the prodromal period, and then down-regulated during the convalescent period. Transcript levels of anti-inflammatory cytokines (IL-10 and TGFß1) and their receptors (IL-10R1 and TßRII), were up-regulated during the prodromal and convalescent periods. Transcript levels of MHCIIß, Igµ, Igτ, TCRδ, TCRß, CD4, and CD8α were altered in SBMIE. Furthermore, expression levels of T-bet, IFN-γ2, RORγ2 and IL-17A/F1 were significantly increased in the initiation of enteritis, whereas the transcript levels of Foxp3 and IL-2/15Ra were significantly up-regulated in the repair of enteritis. In conclusion, grass carp SBMIE is regulated by the adjustment of SBM-based diet intake, and the changes of the above-mentioned genes expression suggest that these genes may be involved in SBMIE.
Assuntos
Ração Animal/análise , Carpas/imunologia , Citocinas/imunologia , Enterite/veterinária , Doenças dos Peixes/imunologia , Trato Gastrointestinal/imunologia , Glycine max/efeitos adversos , Animais , Carpas/metabolismo , Citocinas/genética , Suplementos Nutricionais , Enterite/induzido quimicamente , Enterite/imunologia , Doenças dos Peixes/induzido quimicamente , Trato Gastrointestinal/patologia , Inflamação/genética , Glycine max/químicaRESUMO
Coffee is one of the most popular beverages consumed worldwide. Roasted coffee is a complex mixture of thousands of bioactive compounds, and some of them have numerous potential health-promoting properties that have been extensively studied in the cardiovascular and central nervous systems, with relatively much less attention given to other body systems, such as the gastrointestinal tract and its particular connection with the brain, known as the brain-gut axis. This narrative review provides an overview of the effect of coffee brew; its by-products; and its components on the gastrointestinal mucosa (mainly involved in permeability, secretion, and proliferation), the neural and non-neural components of the gut wall responsible for its motor function, and the brain-gut axis. Despite in vitro, in vivo, and epidemiological studies having shown that coffee may exert multiple effects on the digestive tract, including antioxidant, anti-inflammatory, and antiproliferative effects on the mucosa, and pro-motility effects on the external muscle layers, much is still surprisingly unknown. Further studies are needed to understand the mechanisms of action of certain health-promoting properties of coffee on the gastrointestinal tract and to transfer this knowledge to the industry to develop functional foods to improve the gastrointestinal and brain-gut axis health.
Assuntos
Encéfalo/efeitos dos fármacos , Cafeína/farmacologia , Café/química , Trato Gastrointestinal/efeitos dos fármacos , Anti-Inflamatórios , Antioxidantes/farmacologia , Bebidas , Fibras na Dieta , Microbioma Gastrointestinal , Trato Gastrointestinal/patologia , Humanos , Mucosa , Polímeros , PolifenóisRESUMO
"Candidatus Liberibacter solanacearum" is a pathogen transmitted by the potato psyllid Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) in a persistent manner. In this study, we investigated the molecular interaction between "Ca. Liberibacter solanacearum" and the potato psyllid at the gut interface. Specifically, we focused on the apoptotic response of potato psyllids to the infection by two "Ca. Liberibacter solanacearum" haplotypes, LsoA and LsoB. To this end, we first quantified and localized "Ca. Liberibacter solanacearum" in the gut of adult psyllids. We then evaluated the existence of an apoptotic response in the insect gut using microscopy analyses to visualize the nuclei and the actin cytoskeleton of the gut cells and DNA fragmentation analyses by agarose gel electrophoresis. We also performed annexin V cell death assays to detect apoptosis. Finally, we annotated apoptosis-related genes from the potato psyllid transcriptome and evaluated their expression in response to "Ca. Liberibacter solanacearum" infection. The results showed no cellular markers of apoptosis despite the large amount of "Ca. Liberibacter solanacearum" present in the psyllid gut. In addition, only three genes potentially involved in apoptosis were regulated in the psyllid gut in response to "Ca. Liberibacter solanacearum": the apoptosis-inducing factor AIF3 was downregulated in LsoA-infected psyllids, while the inhibitor of apoptosis IAPP5 was downregulated and IAP6 was upregulated in LsoB-infected psyllids. Overall, no evidence of apoptosis was observed in the gut of potato psyllid adults in response to either "Ca. Liberibacter solanacearum" haplotype. This study represents a first step toward understanding the interactions between "Ca. Liberibacter solanacearum" and the potato psyllid, which is crucial to developing approaches to disrupt their transmission.
Assuntos
Apoptose , Hemípteros/microbiologia , Interações Hospedeiro-Patógeno , Rhizobiaceae/crescimento & desenvolvimento , Animais , Anexina A5/análise , Fragmentação do DNA , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/patologia , Perfilação da Expressão Gênica , Insetos Vetores/microbiologia , Solanum tuberosum/parasitologiaRESUMO
Colorectal cancer (CRC) influences individual health worldwide with high morbidity and mortality. Melatonin, which shows multiple physiological functions (e.g., circadian rhythm, immune modulation, and antioncogenic action), can be present in almost all organisms and found in various tissues including gastrointestinal tract. Notably, melatonin disruption is closely associated with the elevation of CRC incidence, indicating that melatonin is effective in suppressing CRC development and progression. Mechanistically, melatonin favors in activating apoptosis and colon cancer immunity, while reducing proliferation, autophagy, metastasis, and angiogenesis, thereby exerting its anticarcinogenic effects. This review highlights that melatonin can be an adjuvant therapy and be beneficial in treating patients suffering from CRC.