Fecal transplantation from young zebrafish donors efficiently ameliorates the lipid metabolism disorder of aged recipients exposed to perfluorobutanesulfonate

Highlights

• Young fecal transplant promoted the growth of the elderly regardless of PFBS.

• Histological defects in aged PFBS-exposed liver was alleviated by young feces.

• Transplantation of young feces enhanced digestive function of lipids in aged gut.

• PFBS-induced high blood triglyceride in the aged was inhibited by young feces.

• Young fecal transplantation promoted the β-oxidation of fatty acids in aged livers.

Abstract

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 β-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.

Introduction

Nowadays, the size and proportion of world's aging population are growing dramatically, which calls for more care and concern about the health of the elderly. During the progression of aging, the physiological and psychological capability will decline gradually, thereby causing the compromise of wellbeing and life quality (Kundu et al., 2019; D’Amato et al., 2020). In recent years, it is increasingly recognized that gut microbiota plays an important role in the aging process (Kundu et al., 2017; Nicholson et al., 2012). Via the gut-liver and gut-brain axes, a myriad of physiological functions (e.g., lipid metabolism, neuroendocrine, and immune) are under the intimate modulation of the indigenous microbes inhabiting in the gut microenvironment (Turnbaugh et al., 2009; Tremaroli and Bäckhed, 2012). Transplantation of aged gut microbiota to young animal recipients contributes to the impairment of neurotransmission and cognitive functions, underlining the co-evolution of gut microbial community with the aging host (D’Amato et al., 2020). Furthermore, dysbiosis of gut microbiota of an aged host will subsequently induce the onset of typical aging symptoms, including metabolic disorders and systemic inflammation (Thevaranjan et al., 2017). However, accumulative toxicological studies have evidenced the susceptibility of gut health and gut microbiota to the environmental pollutants, among which persistent toxic substances are of high concern to durably and persistently disrupt the gut microbiota by activating the aryl hydrocarbon receptor (AhR) signaling (Chen et al., 2018; Dethlefsen and Relman, 2011; Hu et al., 2021; Jin et al., 2017; Snedeker and Hay, 2012). In this regard, under the context of ubiquitous and severe environmental pollution, the gut microbiota of aged hosts is subjected to significant dysregulation in terms of diversity and metabolism, thus posing additional pressure on the health of the elderly.

Perfluorobutanesulfonate (PFBS) belongs to a large chemical family of per- and polyfluoroalkyl substances (PFASs), which is recently introduced as a fluorosurfactant alternative to replace perfluorooctanesulfonate (PFOS) and has obtained extensive application in a variety of products (Renner, 2006). Because of the shorter carbon chain (C4), PFBS is generally considered less bioaccumulative and less toxic than PFOS (Olsen et al., 2009). However, pollution and bioaccumulation of PFBS have already been detected frequently (Yin et al., 2017). For example, in the groundwater near a PFAS manufactory located in Hubei Province of China, concentration of PFBS is measured to be 2.7 μg/L (Gao et al., 2019). Municipal and industrial discharges also release abundant PFBS into the Tangxun Lake at Hubei Province, China, where the median concentration of PFBS in surface water samples is up to 8.0 μg/L (Shi et al., 2018). Consequently, crucian carps living in Tangxun Lake also accumulate high concentration of PFBS in the blood (Shi et al., 2018), which is expected to enter the human beings in the end during fish consumption. Furthermore, in Arnsberg of Germany, because of the contamination of drinking water by PFASs, PFBS has been prevalently detected in the women, men, and children residents therein (Hölzer et al., 2008). The geometric mean serum elimination half-life of PFBS was previously calculated to be 25.8 days in human subjects (Olsen et al., 2009). Therefore, the environmental pollution and bioaccumulative potential of PFBS are supposed to cause a long-term risk to the health of humans. In particular, the aged population would be more susceptible to the detrimental effects of PFBS due to the declining physiological functions.

In view of the pivotal role of gut microbiota in the maintenance of physiological activities, previous studies have tested and verified the efficacy of fecal transplantation to improve the health of animals that are suffering from metabolic, inflammatory, and mental diseases (Jacob et al., 2017; Smith et al., 2014). Fecal transplantation is a measure to transfer the feces from healthy donors into the gut of sick recipients, aiming to treat the gastrointestinal and extra-gastrointestinal diseases via restoring a healthy gut ecology (Smith et al., 2014). Gut microbiota manipulation by functional feed additives is also efficient to mitigate the adverse effects of environmental pollutants (Chen, 2021; Giommi et al., 2021). Therefore, it appears plausible to transplant the feces of young animals to the aged recipients in an attempt to restore a young-like microbiota, achieve healthy aging status, and enhance the resistance to the toxicity of environmental pollutants. In this study, aged zebrafish were first transplanted with the feces from young zebrafish donors and then exposed to PFBS, aiming to examine the alterations in lipid metabolism along the gut-liver axis, which mediates the close functional and bidirectional communication between the gut and liver systems (Konturek et al., 2018). Due to the high conservation of genetic and physiological pathways, zebrafish has been widely accepted as a good animal model to study human pathogenesis (Bradford et al., 2017). Herein, benefits of young fecal transplant to ameliorate the double stress of aging and PFBS were profiled by integrating transcriptional, biochemical, and histological evidences relevant to lipid metabolism.