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Oral Administration of Brain Protein Combined With Probiotics Induces Immune Tolerance Through the Tryptophan Pathway.

ABSTRACT: Excessive inflammation leads to secondary immune damage after traumatic brain injury (TBI). The intestinal mucosa is a key component of immune tolerance due to gut-brain axis regulation, but the curative effect is not optimal. Intestinal dysfunction impairs the establishment of immune tolerance in patients with TBI. Therefore, we orally administered brain protein (BP) combined with probiotics to induce immune tolerance and explored the mechanism by which the homeostasis of the microbiota contributes to the enhancement of curative effects by BPs. Herein, we demonstrated that patients with TBI and surgical brain injury (SBI) models of rats had obvious dysbiosis. Notably, the intestinal barrier, proinflammatory cytokines, and activation of microglia demonstrated that excessive inflammatory damage was better controlled in the combined group (oral administration of BP combined with probiotics) than in the BP group (oral administration of BP). Fundamentally, tandem mass tag (TMT)-based quantitative proteomics analysis revealed that BP and probiotics preferentially affect Try-related pathways. A series of experiments further confirmed that Indoleamine 2,3 dioxygenase (IDO)/Kynurenine (Kyn)/Aryl hydrocarbon receptor (AhR) expression was high in the BP group, while Tryptophan hydroxylase 1(TpH1)/5-hydroxytryptamine (5-HT) only changed in the combined group. This study suggests that probiotics can enhance the efficacy of oral BP-induced immune tolerance through the Try pathway.

SUBMITTER: Hou Y

PROVIDER: S-EPMC8192843 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundChemotherapy generally causes serious diarrhea and oral mucositis in cancer patients, and subsequently affects treatment. Oral administration of probiotics provides a therapeutic choice to address these limitations. This study aims to conduct a systematic review and meta-analysis on the efficacy of oral probiotic use in the management of the chemotherapy-induced adverse reactions, and to summarize the mechanisms underlying the action.MethodsWe searched PubMed, Embase, ClinicalTrials.gov, and Web of Science from the start of the study to its completion on Dec. 31, 2021. Risk of bias was assessed using Cochrane Collaboration's Tool. Statistical analysis of the acquired data was performed via the RevMan and the Stata Statistical Software. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO registration number: CRD42020220650).ResultsTwelve randomized controlled trials including 1,013 patients were recruited and analyzed via the standard procedure of meta-analysis. In contrast to the control group, orally taking probiotics significantly decreased the risk of chemotherapy-induced diarrhea (≥ 1 grade) (RR = 0.70; 95% Cl: 0.56, 0.88; P = 0.002) and oral mucositis (≥ 1 grade) (RR: 0.84; 95% Cl: 0.78, 0.91; P < 0.00001) at all grades. Further analysis found that severe diarrhea (≥ 2 grades) (RR: 0.50; 95% Cl: 0.32, 0.78; P = 0.002) and severe oral mucositis also significantly declined (≥ 3 grades) (RR: 0.66; 95% Cl: 0.55, 0.79; P < 0.00001) after oral probiotic use. Interestingly, the beneficial effects of probiotics displayed statistically significant only in Asian patients. Importantly, the more species of bacteria they took, the lower the incidences of the adverse reactions occurred. We used Egger's test P value to confirm that there is no publication bias.ConclusionsThis meta-analysis demonstrated that orally administrated probiotics has a potential to decrease chemotherapy-induced diarrhea and oral mucositis incidences. However, the efficacy of oral probiotic use against the adverse reactions needs to be further verified through more clinical trials, and the species and number of probiotics have to be optimized and standardized prior to clinical applications.Systematic review registrationhttps://www.crd.york.ac.uk, identifier: 220650.

Project description:Probiotics have been used successfully to promote human and animal health, but only limited studies have focused on using probiotics to improve the health of hosts of different age. Canine microbiome studies may be predictive of results in humans because of the high structural and functional similarity between dog and human microbiomes. A total of 90 dogs were divided into three groups based on dog age (elderly group, n = 30; young group, n = 24; and training group, n = 36). Each group was subdivided into two subgroups, with and without receiving daily probiotic feed additive. The probiotic feed additive contained three different bacterial strains, namely Lactobacillus casei Zhang, Lactobacillus plantarum P-8, and Bifdobacterium animalis subsp. lactis V9. Serum and fecal samples were collected and analyzed at four different time points, i.e., days 0, 30, and 60 of probiotic treatment, and 15 days after ceasing probiotic treatment. The results demonstrated that probiotics significantly promoted the average daily feed intake of the elderly dogs (P < 0.01) and the average daily weight gain of all dogs (P < 0.05), enhanced the level of serum IgG (P < 0.001), IFN-α (P < 0.05), and fecal SIgA (P < 0.001), while reduced the TNF-α (P < 0.05). Additionally, probiotics could change the gut microbial structure of elderly dogs and significantly increased beneficial bacteria (including some Lactobacillus species and Faecalibacterium prausnitzii) and decreased potentially harmful bacteria (including Escherichia coli and Sutterella stercoricanisin), and the elderly dogs showed the strongest response to the probiotics; the relative abundance of some of these species correlated with certain immune factors and physiological parameters, suggesting that the probiotic treatment improved the host health and enhanced the host immunity by stimulating antibody and cytokine secretion through regulating canine gut microbiota. Furthermore, the gut microbiota of the elderly dogs shifted toward a younger-like composition at day 60 of probiotic treatment. Our findings suggested that the probiotic treatment effects on canine health and immunity were age-related and have provided interesting insights into future development of probiotic-based strategies to improve animal and human health.

Project description:UnlabelledThe heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure.ImportanceThe heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd contamination. Moreover, Cd exposure causes the disruption of the intestinal barrier and further induces the amplification of Cd absorption. The present study confirms that, along with initial intestinal Cd sequestration, oral administration of probiotics can inhibit Cd absorption by protecting the intestinal barrier. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure.

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Oral Administration of Brain Protein Combined With Probiotics Induces Immune Tolerance Through the Tryptophan Pathway.

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