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Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1ß, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.

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The transfer of young fecal microbiota has been found to significantly refresh the reproductive endocrine system and effectively ameliorate the toxicity of perfluorobutanesulfonate (PFBS) in aged zebrafish recipients. However, the mechanisms underlying the antagonistic action of young fecal microbiota against the reproductive endocrine toxicity of PFBS remain largely unknown. In this study, the aged zebrafish were transplanted with feces from young donors and then exposed to PFBS for 14 days. After exposure, the shift in the transcriptomic fingerprint of the gonads was profiled by using high-throughput sequencing, aiming to provide mechanistic clues into the interactive mode of action between young fecal transplantation and PFBS's innate toxicity. The results showed that the gene transcription pattern associated with protein and lipid synthesis in the gonads of the aged individuals was quite different from the young counterparts. It was intriguing that the transplantation of young feces established a youth-like transcriptomic phenotype in the elderly recipients, thus attenuating the functional decline and maintaining a healthy aging state of the gonads. A sex specificity response was clearly observed. Compared to the aged females, more metabolic pathways (e.g., glycine, serine, and threonine metabolism; glyoxylate and dicarboxylate metabolism; pyrimidine metabolism) were significantly enriched in aged males receiving young feces transplants. PFBS dramatically altered the transcriptome of aged testes, while a much milder effect was observable in aged ovaries. Accordingly, a suite of biological processes related to germ cell proliferation were disrupted by PFBS in aged males, including the ECM-receptor interaction, retinol metabolism, and folate biosynthesis. In aged ovaries exposed to PFBS, mainly the fatty acid and arginine biosynthesis pathway was significantly affected. However, these transcriptomic disorders caused by PFBS were largely mitigated in aged gonads by transferring young feces. Overall, the present findings highlighted the potential of young fecal transplantation to prevent the functional compromise of gonads resulting from aging and PFBS.

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Perfluorobutanesulfonate (PFBS) is an emerging pollutant of potent toxicity to impair visual system. Previous studies highlighted the applicability of gut microbiota manipulation to mitigate the toxicities of PFBS. However, it remains unknown whether transplantation of whole fecal microbiota to PFBS-disturbed gut can restore the health of the recipient animals, especially for aged fish that are of high susceptibility. In the present study, aged zebrafish of 3 years old were first transplanted with feces from young counterparts and then exposed to environmentally relevant concentrations of PFBS. After exposure, toxic effects of PFBS on visual system of aged zebrafish were elucidated based on transcriptional, proteomic, biochemical, histological, and behavioral evidences. In addition, interaction between young fecal transplant and innate visual toxicity of PFBS was further explored in the aged. The results showed that PFBS singular exposure induced lipid peroxidation (by 1.9-fold) in aged male eyes, which were alleviated by young fecal transplantation. PFBS also disturbed the retinal structure of the aged, which was characterized by increases in plexiform layers, but decreases in ganglion neuron number (by 26.8% and 26.0% in males and females, respectively) and optic nerve width (by 14.1% and 12.7% in males and females, respectively). It was unexpected that young fecal transplant was very potent in re-organizing the histological assembly of aged eyes regardless of PFBS coexposure, underlining the intimate interplay between gut and retina. Proteomic profiling provided more clues about the visual toxicology mechanism of PFBS, which was found to typically interfere with synaptic neurotransmission occurring in plexiform layers. However, proteome perturbation of aged eyes by PFBS exposure was effectively shifted by the transplantation of young feces towards the control phenotype, suggesting the high ameliorative potential of young fecal transplantation along the gut-retina axis. Overall, the present study pinpoints the potent visual toxicity of PFBS in aged animals and highlights the efficacy of young fecal transplant to regulate the inherent toxicity of PFBS. Future studies are necessitated to sequence the gut microbiota and unveil the underlying interactive routes between gut microbes and visual system.

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The aging process leads to the gradual impairment of physiological functions in the elderly, making them more susceptible to the toxicity of environmental pollutants. In this study, aged zebrafish were first transplanted with the feces from young donors and subsequently exposed to perfluorobutanesulfonate (PFBS), an emerging persistent toxic pollutant. The interaction between young fecal transplant and PFBS inherent toxicity was investigated, focusing on reproductive performance and the underlying endocrine mechanism. The results showed that PFBS single exposure increased the percentage of primary oocytes in aged ovaries, implying a blockage of oogenesis. However, transplantation of young feces completely abolished the effects of PFBS and promoted oocyte growth, as inferred by the obviously lower percentage of primary oocytes, accompanied by a higher percentage of cortical-alveolar oocytes. Measurement of sex hormones found that PFBS significantly increased the blood concentration of estradiol and disrupted the balance of sex hormones in the elderly, which were, however, efficiently ameliorated by young fecal transplantation. Based on gene transcription along the hypothalamic-pituitary-gonadal axis, hierarchical clustering analysis showed similar profiles of the reproductive endocrine system between young zebrafish and their aged counterparts transplanted with young feces, implying that young fecal transplantation might refresh the endocrine system of aged recipients, regardless of PFBS exposure. The increased transcription levels of mRNAs encoding vitellogenin, activinBA, and membrane bound progestin receptors would cooperatively enhance the growth and maturation of oocytes in the ovaries of aged zebrafish receiving young fecal transplantation. Overall, the findings highlighted the potent efficacy of young fecal transplantation to improve the reproductive function of the elderly and to mitigate the endocrine disruption of an environmental pollutant. These findings are expected to broaden our understanding of the efficacy, mechanisms, and application of fecal transplantation.

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Perfluorobutanesulfonate (PFBS) is an environmental pollutant of emerging concern, which significantly impacts the metabolism and health of animals. Because of the loss of functional capacity, the aged animals are regarded more susceptible to the toxicity of environmental pollutants. In the present study, aged zebrafish were employed as the toxicological animal and transplanted with the feces collected from young donors for 14 days, after which the acclimated elderly were exposed to PFBS at environmentally relevant concentrations (0 and 100 µg/L) for another 14 days. When the exposure was concluded, glucose metabolic disturbances of PFBS in the aged and efficacy of young fecal transplant to mitigate the toxicity of PFBS were explored along the gut-liver axis. The results showed that PFBS exposure significantly inhibited the enzymatic activity of α-amylase in the gut, but increased the alanine aminotransferase (ALT) activity in the blood of the aged zebrafish, suggesting the impairment of intestinal digestive functions of carbohydrates and the induction of liver damage by PFBS. However, young fecal transplantation successfully ameliorated the toxicity of PFBS on α-amylase and ALT, underlining the benefits conveyed to the health of the elderly. In addition, transplantation of young feces was efficient to alleviate the hyperglycemia symptom in the elderly via stimulating the secretion of insulin. PFBS exposure increased blood glucagon level, disrupted insulin receptor transcription, and depleted hepatic glycogen store, which were all mitigated by young fecal transplant. Hepatic proteomic analysis also found dynamic interactions between young fecal transplantation and PFBS pollutant on the metabolic pathways of glucose and glycogen, involving glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis. Overall, the present findings highlighted the beneficial effects of young fecal transplantation to protect the aged from the glucose metabolism toxicity of PFBS, thus providing a plausible measure to improve the health aging status.

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Aging is a biological process that is accompanied by the gradual loss of physiological functions. Under the context of ubiquitous and persistent environmental pollution, the elderly will be more vulnerable to the detrimental effects of toxic pollutants than the young. With objectives to explore effective measures to ameliorate the double stress of aging and toxicants, the present study transplanted the feces from young zebrafish donors to aged recipients, which were concurrently exposed to perfluorobutanesulfonate (PFBS), an emerging environmental pollutant of international concern. After exposure, growth, hepatic structural organization, and lipid metabolism were examined. The results showed that, irrespective of PFBS toxicity, transplantation of young feces significantly enhanced the growth of the aged. In the livers of aged and PFBS-exposed zebrafish, vacuolization symptom was prevalently observed, while young fecal transplantation alleviated the structural defects in aged livers. In the gut of the elderly, digestive activity of lipids was promoted after the transplantation of young feces. The blood of the aged females accumulated significantly higher concentration of triglyceride (TG) than the young counterparts (2.6-fold), implying that the elderly were at high risk of cardiovascular diseases. PFBS treatment of the aged further increased blood TG levels by 2.0-fold relative to the aged control group, pointing to the aggravation of the health of the elderly by environmental pollution. However, it is intriguing that young fecal transplantation efficiently inhibited the metabolic toxicity of PFBS and restored the normal level of blood TG, which provided more evidence about the benefit of young fecal transplant to improve the health of the aged individuals. In the aged livers transplanted with young feces, mitochondrial ß-oxidation of fatty acids was consistently activated. Overall, the present study verified the efficacy of young fecal transplantation to mitigate the metabolic disorders resulting from aging and an environmental pollutant.

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