An integrated mycotoxin-mitigating agent can effectively mitigate the combined toxicity of AFB1, DON and OTA on the production performance, liver and oviduct health in broiler breeder hens.

This study was to evaluate the efficacy of an integrated mycotoxin-mitigating agent in reducing the adverse effects of co-occurring dietary aflatoxin B1 deoxynivalenol and ochratoxin A on broiler breeder hens. 360 30-week-old Hubbard Efficiency Plus broiler breeder hens were allocated into four groups and received a basal diet (BD; Control), BD added 0.15 mg/kg aflatoxin B1+1.5 mg/kg deoxynivalenol+0.12 mg/kg ochratoxin A (Toxins), BD plus Toxins with 0.1% TOXO-XL (Toxins + XL1), and BD plus Toxins with 0.2% TOXO-XL (Toxins + XL2), respectively, for 8 weeks, and then received the same BD for another 4 weeks. Compared with control, mycotoxins decreased total egg weigh, egg laying rate, settable eggs rate, hatch of total eggs rate, egg quality, but increased feed/egg ratio and mortality rate, and impaired the liver and oviduct health during weeks 1-8 and(or) 9-12. It also increased PC and MDA concentrations, TUNEL-positive cells and IL-1ß and IL-6 expression, and decreased T-AOC, GPX and CAT activities in liver and/or oviduct. Notably, most of these negative changes were mitigated by both dosages of TOXO-XL. Generally, 0.2% TOXO-XL displayed better mitigation effects than 0.1% TOXO-XL. Conclusively, these findings revealed that TOXO-XL could mitigate the combined mycotoxins-induced toxicity on the performance, liver and oviduct health, through the regulation of redox, immunity, and apoptosis in broiler breeder hens.

Mitigating the adverse effects of Aflatoxin B1 in LMH, IPEC-J2 and 3D4/21 cells by a novel integrated agent.

This study was to evaluate the efficacy of TOXO-XL (XL), an integrated mycotoxin-mitigating agent, on aflatoxin B1 (AFB1)-induced damage in Leghorn male hepatoma (LMH), porcine jejunum epithelial cell line (IPEC-J2) and porcine alveolar macrophages (3D4/21) cells, and to explore its potential mechanisms. The results showed that 30% inhibition concentration (IC30) of AFB1 in LMH, IPEC-J2 and 3D4/21 cells was 0.5, 15.0, and 2.5 mg/L, respectively. Notably, cell viability, ROS, apoptosis and DNA lesion induced by AFB1 (IC30) could be ameliorated by the supplementation with XL at the dosage of 0.025, 0.025 and 0.005%, respectively. Additionally, the migration and phagocytosis abilities impaired by AFB1 were also restored by XL in 3D4/21. Further experiments revealed that XL supplementation markedly attenuated AFB1-induced inflammatory response by decreasing IL-1ß, IL-6 and IL-10 in LMH, IL-6 in IPEC-J2 and IL-1ß in 3D4/21 cells. Meanwhile, XL supplementation reversed the alterations of BAX, BCL-2 and caspase-3 induced by AFB1 in the three cells, suggesting that AFB1-induced apoptosis may be suppressed via the mitochondria-dependent pathway. Furthermore, XL may have a protective effect on the intestinal barrier through the restoration of occludin protein. Conclusively, these findings indicated that XL could alleviate AFB1-induced cytotoxicity in the three cells, potentially through the regulation of cytokines, ROS, apoptotic and DNA damage signaling.

Repeated and multiple fecal microbiota transplantations plus partial enteral nutrition as the first-line treatment in active pediatric Crohn's disease.

Background: Most studies have reported fecal microbiota transplantation (FMT) as an effective secondary option for Crohn's disease (CD). However, there is little data on FMT as a first-line treatment for CD. In our study we explore the rates of clinical and endoscopic remission and mucosal healing after FMT plus partial enteral nutrition (PEN), as a first-line treatment for active CD in children. Methods: We retrospectively enrolled pediatric CD patients who underwent PEN or PEN plus FMT treatment at diagnosis from November 2016 to July 2019 at the Pediatric Department, Tongji Hospital. The two groups were defined as FMT group (repeated and multiple doses of FMT plus PEN) or PEN group (PEN alone). All the patients received PEN intervention. At baseline and week 8- 10, the FMT group was administered multiple doses of FMT to help induce and maintain remission. All patients were evaluated at week 8- 10 and 18-22 via clinical and relevant laboratory parameters and endoscopic results. The clinical and endoscopic remission and mucosal healing rates were compared between the two groups at different time points after the therapy. Results: Twenty-five newly diagnosed active CD patients were included in the study, containing 7 females and 18 males with a median age of 11. 1 ± 2.3 years. 13 and 12 patients were assigned to the PEN and FMT groups, respectively. At week 8-10, clinical remission was obtained in 83.3% and 53.8% of the FMT and PEN groups, respectively (p=0.202). The endoscopic remission rates were 72.7% for FMT and 25.0% for PEN (p=0.039), whereas the mucosal healing rates were 27.2% for FMT and 0% for PEN (p=0.093). At week 18-22, clinical remission was achieved in 72.7% and 20.0% of patients in the FMT and PEN groups, respectively (p=0.03). Theendoscopic remission rates were 66.6% and 12.5% in the FMT and PEN groups, respectively (p=0.05), whereas the mucosal healing rates were 55.5% and 0% in FMT and PEN groups, respectively (p=0.029). Conclusion: This study demonstrate that FMT plus PEN can be used as a first-line treatment for active CD in children.

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study.

Background: Fecal microbiota transplantation (FMT) is an effective treatment for intestinal and extra-intestinal disorders. Nonetheless, long-term safety and efficacy remain major challenges for FMT applications. To date, few long-term follow-up studies have been published on FMT in children. Methods: Retrospective reviewed the medical charts of 74 patients who underwent 508 FMT courses between August 2014 and July 2019 at our medical center. All the FMT procedures followed uniform standards. Baseline characteristics pre-FMT and follow-up data were collected at 1, 3, 6, 12, 36, 60, and 84 months after FMT. All potential influencing factors for adverse events (AEs) were analyzed and assessed using regression analyses. Results: A total of 70 (13.7%) short-term AEs occurred in twenty-six patients (35.1%). Most AEs (88.5%) occurred within 2 days post-FMT. A total of 91.4% of the AEs were self-limiting. Ulcerative colitis (UC) and within four times of FMT were associated with a higher rate of AEs (p = 0.028 and p = 0.021, respectively). The primary clinical remission rate after FMT was as high as 72.9%. Twenty-five children were followed for more than 5 years after FMT. The clinical remission rates gradually decreased over time after FMT. During follow-up, none of the patients developed autoimmune, metabolic, or rheumatologic disorders or tumor-related diseases. However, nine children developed rhinitis, five developed rhinitis, were underweight, and six developed constipation. Conclusions: FMT is a safe and effective treatment for dysbiosis in children. The long-term efficacy of FMT for each disease decreased over time. Moreover, multiple FMTs are recommended 3 months post-FMT for recurrent diseases.

Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment.

AIM: To investigate the impact of fecal microbiota transplantation (FMT) treatment on allergic colitis (AC) and gut microbiota (GM). METHODS: We selected a total of 19 AC infants, who suffered from severe diarrhea/hematochezia, did not relieve completely after routine therapy or cannot adhere to the therapy, and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT, and GM composition was assessed for infants and donors using 16S rDNA sequencing analysis. RESULTS: After FMT treatment, AC symptoms in 17 infants were relieved within 2 d, and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to follow-up. During follow-up, one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16S rDNA analysis in ten AC infants, most of them (n = 6) had greater GM diversity after FMT. As a result, Proteobacteria decreased (n = 6) and Firmicutes increased (n = 10) in post-FMT AC infants. Moreover, Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level, Bacteroides (n = 6), Escherichia (n = 8), and Lactobacillus (n = 4) were enriched in some AC infants after FMT treatment, but the relative abundances of Clostridium (n = 5), Veillonella (n = 7), Streptococcus (n = 6), and Klebsiella (n = 8) decreased dramatically. CONCLUSION: FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.