A gut microbial metabolite cocktail fights against obesity through modulating the gut microbiota and hepatic leptin signaling.

BACKGROUND: Excessive body weight and obesity elevate the risk of chronic non-communicable diseases. The judicious application of the gut microbiome, encompassing both microorganisms and their derived compounds, holds considerable promise in the treatment of obesity. RESULTS: In this study, we showed that a cocktail of gut microbiota-derived metabolites, comprising indole 3-propionic acid (IPA), sodium butyrate (SB) and valeric acid (VA), alleviated various symptoms of obesity in both male and female mice subjected to a high-fat diet (HFD). The 16S ribosomal RNA (rRNA) sequencing revealed that administering the cocktail via oral gavage retained the gut microbiota composition in obese mice. Fecal microbiota transplantation using cocktail-treated mice as donors mitigated the obesity phenotype of HFD-fed mice. Transcriptomic sequencing analysis showed that the cocktail preserved the gene expression profile of hepatic tissues in obese mice, especially up-regulated the expression level of leptin receptor. Gene delivery via in vivo fluid dynamics further validated that the anti-obesity efficacy of the cocktail was dependent on leptin signaling at least partly. The cocktail also inhibited the expression of appetite stimulators in hypothalamus. Together, the metabolite cocktail combated adiposity by retaining the gut microbiota configuration and activating the hepatic leptin signaling pathway. CONCLUSIONS: Our findings provide a sophisticated regulatory network between the gut microbiome and host, and highlight a cocktail of gut microbiota-derived metabolites, including IPA, SB, and VA, might be a prospective intervention for anti-obesity in a preclinical setting. © 2024 Society of Chemical Industry.

Caloric restriction alleviates radiation injuries in a sex-dependent fashion.

Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sex-specific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.

Social Hierarchy Dictates Intestinal Radiation Injury in a Gut Microbiota-Dependent Manner.

Social hierarchy governs the physiological and biochemical behaviors of animals. Intestinal radiation injuries are common complications connected with radiotherapy. However, it remains unclear whether social hierarchy impacts the development of radiation-induced intestinal toxicity. Dominant mice exhibited more serious intestinal toxicity following total abdominal irradiation compared with their subordinate counterparts, as judged by higher inflammatory status and lower epithelial integrity. Radiation-elicited changes in gut microbiota varied between dominant and subordinate mice, being more overt in mice of higher status. Deletion of gut microbes by using an antibiotic cocktail or restructuring of the gut microecology of dominant mice by using fecal microbiome from their subordinate companions erased the difference in radiogenic intestinal injuries. Lactobacillus murinus and Akkermansia muciniphila were both found to be potential probiotics for use against radiation toxicity in mouse models without social hierarchy. However, only Akkermansia muciniphila showed stable colonization in the digestive tracts of dominant mice, and significantly mitigated their intestinal radiation injuries. Our findings demonstrate that social hierarchy impacts the development of radiation-induced intestinal injuries, in a manner dependent on gut microbiota. The results also suggest that the gut microhabitats of hosts determine the colonization and efficacy of foreign probiotics. Thus, screening suitable microbial preparations based on the gut microecology of patients might be necessary in clinical application.

Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury.

Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.

Openness to experience and dispositional awe: The moderating role of subjective socioeconomic status and mediating role of Zhong-Yong thinking style in Chinese undergraduates.

Existing research has established that openness to experience can enhance dispositional awe. For the first time, the current study examines whether subjective socioeconomic status (SSES) moderates and a Zhong-Yong thinking style mediates this effect. A sample of 2,377 Chinese undergraduates (mean age 20.7, ranging from 18 to 26) was recruited. As shown in previous research, openness was found to be positively associated with dispositional awe. As predicted, the relationship was moderated by familial and school SSES. The positive correlation was significantly larger in cases of lower familial and school SSES. The mediating effect of Zhong-Yong thinking style was also supported in the relationship between openness and dispositional awe, as was the moderating effect of familial SSES; however, a suppressive effect was found for school SSES. The implications of this study are discussed herein.

MiR-365 enhances the radiosensitivity of non-small cell lung cancer cells through targeting CDC25A.

Radioresistance is a major challenge in lung cancer radiotherapy (RT), and consequently, new radiosensitizers are urgently needed. MicroRNAs (miRNAs) have been demonstrated to participate in many important cellular processes including radiosensitization. MiR-365 is dysregulated in non-small cell lung cancer (NSCLC) and is able to restrain the development of NSCLC. However, the relationship between miR-365 and radiosensitivities of NSCLC cells remains largely unknown. Here we reveal that overexpression of miR-365 is able to enhance the radiosensitivity of NSCLC cells through targeting CDC25A. We found that the expression level of miR-365 was positively correlated with the radiosensitivity of NSCLC cell lines. Furthermore, our results showed that overexpression of miR-365 could sensitize A549 cells to the irradiation. However, knockdown of miR-365 in H460 cells could act the converse manner. Mechanically, miR-365 was able to directly target 3'UTR of cell division cycle 25A (CDC25A) mRNA and reduce the expression of CDC25A at the levels of mRNA and protein. And we confirmed that miR-365 could increase the radiosensitivity of NSCLC cells by targeting CDC25A using in vitro and in vivo assays. Taken together, restoration of miR-365 expression enhances the radiosensitivity of NSCLC cells by suppressing CDC25A, and miR-365 could be used as a radiosensitizer for NSCLC therapy.

Cordycepin sensitizes breast cancer cells toward irradiation through elevating ROS production involving Nrf2.

Radiation therapy toward malignancies is often ineffective owing to radioresistance of cancer cells. On the basis of anti-tumor properties of cordycepin, we examined the effects of cordycepin on sensitizing breast cancer cells toward radiotherapy. Cordycepin administration promoted G2/M arrest and apoptosis of MCF-7 and MDA-MB-231 cells resulting in restraining the proliferation of the cells in vitro and in vivo following irradiation. Mechanistic investigations showed that the breast cancer cells cultured with cordycepin harbored higher levels of intracellular reactive oxygen species (ROS) and incremental numbers of γ-H2AX foci after irradiation exposure. Importantly, cordycepin treatment down-regulated the expression levels of Nuclear factor erythroid 2-related factor (Nrf2) and a series of downstream genes, such as heme oxygenase-1 (HO-1), to enhance ROS in breast cancer cells exposed to irradiation. Together, our observations demonstrate that cordycepin treatment sensitizes breast carcinoma cells toward irradiation via Nrf2/HO-1/ROS axis. Thus, our findings provide novel insights into the function and the underlying mechanism of cordycepin in radiotherapy, and suggest that cordycepin might be employed as a radiosensitizer during radiotherapy toward breast cancer in a pre-clinical setting.

Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings.

B7-H3 regulates lipid metabolism of lung cancer through SREBP1-mediated expression of FASN.

B7-H3 is a glycoprotein overexpressed in cancer, but its functional contribution in this setting remains poorly understood. In the present study, we identified that the overexpression of B7-H3 in lung cancer resulted in aberrant lipid metabolism via SREBP-1/FASN signaling pathway. Immunohistochemical analysis of tissue microarrays revealed that approximately 80.4% (37/46) of lung cancer tissues were positive for B7-H3 accompanying poor prognosis. Notably, Oil red O staining and total triglyceride assay exhibited that down-regulation of B7-H3 decreased lipid synthesis in lung cancer A549 and H446 cell lines. Mechanistic investigations showed that B7-H3 modulated the expression of FASN, a fatty acid synthase, specifically. Furthermore, deletion of B7-H3 down-regulated the mRNA and protein levels of SREBP-1, a transcription factor governing the expression of FASN. Finally, correlation analysis between expression levels of B7-H3 and FASN exhibited a positive correlation in clinical lung cancer tissues. Overall, we conclude that B7-H3 hijacks SREBP-1/FASN signaling mediating abnormal lipid metabolism in lung cancer. Our finding provides new insights into the function and mechanism of B7-H3 in the development of lung cancer.

Total abdominal irradiation exposure impairs cognitive function involving miR-34a-5p/BDNF axis.

Radiotherapy is often employed to treat abdominal and pelvic malignancies, but is frequently accompanied by diverse acute and chronic local injuries. It was previously unknown whether abdominal and pelvic radiotherapy impairs distant cognitive dysfunction. In the present study, we demonstrated that total abdominal irradiation (TAI) exposure caused cognitive deficits in mouse models. Mechanically, microarray assay analysis revealed that TAI elevated the expression level of miR-34a-5p in small intestine tissues and peripheral blood (PD), which targeted the 3'UTR of Brain-derived neurotrophic factor (Bdnf) mRNA in hippocampus to mediate cognitive dysfunction. Tail intravenous injection of miR-34a-5p antagomir immediately after TAI exposure rescued TAI-mediated cognitive impairment via blocking the up-regulation of miR-34a-5p in PD, resulting in restoring the Bdnf expression in the hippocampus. More importantly, high throughput sequencing validated that the gut bacterial composition of mice was shifted after TAI exposure, which was retained by miR-34a-5p antagomir injection. Thus, our findings provide new insights into pathogenic mechanism underlying abdominal and pelvic radiotherapy-mediated distant cognitive impairment.

Circadian Rhythm Shapes the Gut Microbiota Affecting Host Radiosensitivity.

Modern lifestyles, such as shift work, nocturnal social activities, and jet lag, disturb the circadian rhythm. The interaction between mammals and the co-evolved intestinal microbiota modulates host physiopathological processes. Radiotherapy is a cornerstone of modern management of malignancies; however, it was previously unknown whether circadian rhythm disorder impairs prognosis after radiotherapy. To investigate the effect of circadian rhythm on radiotherapy, C57BL/6 mice were housed in different dark/light cycles, and their intestinal bacterial compositions were compared using high throughput sequencing. The survival rate, body weight, and food intake of mice in diverse cohorts were measured following irradiation exposure. Finally, the enteric bacterial composition of irradiated mice that experienced different dark/light cycles was assessed using 16S RNA sequencing. Intriguingly, mice housed in aberrant light cycles harbored a reduction of observed intestinal bacterial species and shifts of gut bacterial composition compared with those of the mice kept under 12 h dark/12 h light cycles, resulting in a decrease of host radioresistance. Moreover, the alteration of enteric bacterial composition of mice in different groups was dissimilar. Our findings provide novel insights into the effects of biological clocks on the gut bacterial composition, and underpin that the circadian rhythm influences the prognosis of patients after radiotherapy in a preclinical setting.

Roseburia intestinalis sensitizes colorectal cancer to radiotherapy through the butyrate/OR51E1/RALB axis.

The radioresistant signature of colorectal cancer (CRC) hampers the clinical utility of radiotherapy. Here, we find that fecal microbiota transplantation (FMT) potentiates the tumoricidal effects of radiation and degrades the intertwined adverse events in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. FMT cumulates Roseburia intestinalis (R. intestinalis) in the gastrointestinal tract. Oral gavage of R. intestinalis assembles at the CRC site and synthetizes butyrate, sensitizing CRC to radiation and alleviating intestinal toxicity in primary and CRC hepatic metastasis mouse models. R. intestinalis-derived butyrate activates OR51E1, a G-protein-coupled receptor overexpressing in patients with rectal cancer, facilitating radiogenic autophagy in CRC cells. OR51E1 shows a positive correlation with RALB in clinical rectal cancer tissues and CRC mouse model. Blockage of OR51E1/RALB signaling restrains butyrate-elicited autophagy in irradiated CRC cells. Our findings highlight that the gut commensal bacteria R. intestinalis motivates radiation-induced autophagy to accelerate CRC cell death through the butyrate/OR51E1/RALB axis and provide a promising radiosensitizer for CRC in a pre-clinical setting.

Sensitive and selective detection of p-nitroaniline with the assistance of a fluorescence capillary imprinted sensor.

A fluorescence capillary imprinted sensor was first prepared with high selectivity and sensitivity for the detection of p-nitroaniline. The fluorescence imprinted polymer prepared by the sol-gel method using blue CdTe quantum dots as the fluorescence source was self-sucked into an activated capillary to form the fluorescence imprinted capillary (CdTe@FMIP-CA) sensor. The specificity and selectivity tests showed that the CdTe@FMIP-CA sensor has a high selective recognition ability toward p-nitroaniline. The CdTe@FMIP-CA sensor can quickly and specifically recognize p-nitroaniline within 2 min with a high specific fluorescence response efficiency. The fluorescence intensity of the CdTe@FMIP-CA sensor remained stable within 60 min. A good linear relationship was established between the fluorescence quenching efficiency of the CdTe@FMIP-CA sensor with a p-nitroaniline concentration range of 0.2-100 µmol L-1 with the detection limit of 4.6 nmol L-1 and the quantitation limit of 0.2 µmol L-1. The imprinting factor was calculated as 3.88. The method has been successfully applied for the determination of trace p-nitroaniline in lake water, tap water, urine, and serum samples. The CdTe@FMIP-CA sensor realized the sensitive and selective detection of p-nitroaniline with the lower consumption of microvolume reagent (18 µL per time), which provided a novel strategy for highly sensitive analysis of microvolume trace pollutants.

Abbreviated version of Penn State Worry Questionnaire for Chinese adolescents: Age, gender and longitudinal invariance.

The abbreviated version of Penn State Worry Questionnaire (PSWQ-A) has been widely used to assess worry. However, its measurement invariance has been not yet warranted. With a cross-sectional and a longitudinal sample of Chinese adolescents (N1 = 1,329, N2 = 408), this study examined age, gender, and longitudinal invariance of PSWQ-A. Results supported strict invariance, including configural, metric, scalar, and error level, across gender and age in the cross-sectional sample; strict longitudinal measurement invariance was also supported in the longitudinal sample. This study suggests the application of the PSWQ-A in measuring adolescent worry and a basis for comparisons of different populations and occasions for worry.

Applicability of the cognitive model of generalized anxiety disorder to adolescents' sleep quality: A cross-sectional and longitudinal analysis.

Background: Poor sleep quality is a prevalent health issue among adolescents, and few studies have examined the variables affecting adolescents' sleep quality from the perspective of the co-occurrence of sleep issues and anxiety disorders. Therefore, the current study investigated whether the cognitive model of generalized anxiety disorder applies to adolescents' sleep quality. Method: In Study 1, a total of 2042 adolescents were recruited and they completed questionnaires relating to worry, intolerance of uncertainty (IU), negative problem orientation (NPO), cognitive avoidance (CA), and sleep quality. In Study 2, a total of 379 adolescents participated in a six-month longitudinal survey to verify the model that was obtained in Study 1. Results: Study 1 showed the modified cognitive model of generalized anxiety disorder can be applied to adolescents' sleep quality. Specifically, IU was a higher-order vulnerability factor that directly affected worry, and indirectly fostered worry via NPO and CA, where worry only mediated the relationships between IU, NPO, and sleep quality. However, CA exerted no independent effect on worry or sleep quality beyond the influences of IU and NPO, therefore, it dropped out of the final model. Study 2 partially confirmed the above model again from the longitudinal perspective. Conclusion: The present study constructs a new model to explain adolescents' sleep quality, providing a foundation for future interventions.

Stable colonization of Akkermansia muciniphila educates host intestinal microecology and immunity to battle against inflammatory intestinal diseases.

Gut microbial preparations are widely used in treating intestinal diseases but show mixed success. In this study, we found that the therapeutic efficacy of A. muciniphila for dextran sodium sulfate (DSS)-induced colitis as well as intestinal radiation toxicity was ~50%, and mice experiencing a positive prognosis harbored a high frequency of A. muciniphila in the gastrointestinal (GI) tract. Stable GI colonization of A. muciniphila elicited more profound shifts in the gut microbial community structure of hosts. Coexisting with A. muciniphila facilitated proliferation and reprogrammed the gene expression profile of Lactobacillus murinus, a classic probiotic that overtly responded to A. muciniphila addition in a time-dependent manner. Then, a magnetic-drove, mannose-loaded nanophase material was designed and linked to the surface of A. muciniphila. The modified A. muciniphila exhibited enhancements in inflammation targeting and intestinal colonization under an external magnetic field, elevating the positive-response rate and therapeutic efficacy against intestinal diseases. However, the unlinked cocktail containing A. muciniphila and the delivery system only induced negligible improvement of therapeutic efficacy. Importantly, heat-inactivated A. muciniphila lost therapeutic effects on DSS-induced colitis and was even retained in the GI tract for a long time. Further investigations revealed that the modified A. muciniphila was able to drive M2 macrophage polarization by upregulating the protein level of IL-4 at inflammatory loci. Together, our findings demonstrate that stable colonization of live A. muciniphila at lesion sites is essential for its anti-inflammatory function.

Marasmius androsaceus mitigates depression-exacerbated intestinal radiation injuries through reprogramming hippocampal miRNA expression.

INTRODUCTION: Cancer patients commonly experience high levels of psychological stress, which poses significant risks to their well-being. Radiotherapy is a primary treatment modality for cancer; however, it often leads to intestinal injuries in these patients. Nevertheless, the impact of mental stress on radiotherapy-intertwined complications remains unclear. METHODS: To induce intestinal injury, we employed total abdominal irradiation in our experimental model. We conducted high-throughput sequencing to analyze the expression profile of miRNAs in the hippocampus. RESULTS: We observed that mice with depression exhibited more severe intestinal injuries following total abdominal irradiation. Remarkably, oral administration of Marasmius androsaceus not only alleviated the depressive phenotype but also mitigated radiation-induced intestinal toxicity. Notably, this radioprotective effect was not observed in mice without depression. Depression disrupted the hippocampal miRNA expression profile in mice subjected to local irradiation of the abdomen, leading to the accumulation of miR-139-5p and miR-184-3p in the hippocampus, serum, and small intestine tissues. However, treatment with Marasmius androsaceus reprogrammed the miRNA expression signature in mice with depression. Furthermore, intravenous injection of antagomirs targeting miR-139-5p and miR-184-3p ameliorated depression, up-regulated Spn expression, reduced radiation enteritis, and improved the integrity of the small intestine in irradiated mice. CONCLUSION: Our findings demonstrate the efficacy of Marasmius androsaceus, a small mushroom, in alleviating depression-aggravated intestinal toxicity following radiotherapy by reprogramming hippocampal miRNA expression.

Sexual dimorphism in gut microbiota dictates therapeutic efficacy of intravenous immunoglobulin on radiotherapy complications.

INTRODUCTION: With the mounting number of cancer survivors, the complications following cancer treatment become novel conundrums and starve for countermeasures. Intravenous immunoglobulin (IVIg) is a purified preparation for immune-deficient and autoimmune conditions. OBJECTIVES: Here, we investigated whether IVIg could be employed to fight against radiation injuries and explored the underlying mechanism. METHODS: Hematopoietic or gastrointestinal (GI) tract toxicity was induced by total body or abdominal local irradiation. High-throughput sequencing was performed to analyze the gut microbiota configurations and gene expression profile of small intestine. The untargeted metabolomics of gut microbiome was assessed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analyses. Hydrodynamic-based gene delivery was used to knockdown the target genes in vivo. RESULTS: Intravenous injection of IVIg protected against radiation-induced hematopoietic and GI tract toxicity in female mice but not in males. IVIg structured sex-characteristic gut microbiota configurations in abdominal irradiated mice. The irradiation enriched gut Lachnospiraceae in female mice but reduced those in males. IVIg injection combined with oral gavage of Lachnospiraceae or its metabolite hypoxanthine, alleviated radiation toxicity in male mice however, Lachnospiraceae or hypoxanthine alone failed to ameliorate the injuries. Abdominal local irradiation drove sex-distinct gene expression signatures in small intestine. Mechanistic investigation showed that replenishment of Lachnospiraceae or hypoxanthine offset abdominal radiation-reduced PLD1 expression in male mice. In females, irradiation elevated PLD1 expression. Deletion of PLD1 in GI tract of female mice erased the radioprotective effects of IVIg. CONCLUSION: IVIg battles against radiation injuries in a sex-specific, gut microbiome-dependent way through Lachnospiraceae/hypoxanthine/PLD1 axis. Our findings provide a sex-precise therapeutic avenue to improve the prognosis of cancer patients with radiotherapy in pre-clinical settings.

Description of three new Boulenophrys species from eastern Guangdong, China, emphasizing the urgency of ecological conservation in this region (Anura, Megophryidae).

The hilly region in eastern Guangdong, China lacks comprehensive scientific investigations for decades, especially in terms of herpetofauna. In recent years, several highly threatened amphibians have been gradually discovered from this region. In this work, three new species of the genus Boulenophrys are described, which are endemic from only one or two known localities in eastern Guangdong. These discoveries enrich the diversity of Boulenophrys in eastern Guangdong. With the large number of threatened urodeles and anuran species occurring in this densely populated area, the unique herpetological diversity in eastern Guangdong is facing the impacts of habitat degradation and fragmentation, and conservation actions are urgently required.

Ambient temperature structures the gut microbiota of zebrafish to impact the response to radioactive pollution.

Potential nuclear accidents propel serious environmental pollution, and the resultant radionuclide release devastates severely the environment severely and threatens aquatic organism survival. Likewise, ongoing climate change coupled with the gradual increase in global surface temperatures can also adversely impact the aquatic ecosystems. In the present study, we preconditioned zebrafish (Danio rerio) at three different temperatures (18 °C, 26 °C and 34 °C) to investigate the effects of a temperature profile on their radiosensitivity (exposure to 20 Gy of gamma rays) to identify the potential biochemical mechanism responsible for influencing radiosensitivity. We found that preconditioning of zebrafish at different temperatures moulded specific gut microbiota configurations and impacted hepatic glycometabolism and sensitivity to subsequent radiation. Following antibiotic treatment to reduce gut bacteria, these observed differences in the expression of hepatic glycometabolism-related genes and radiation-induced intestinal toxicity were minimal, supporting the hypothesis that the gut bacteria reshaped by different ambient temperatures might be the key modulators of hepatic functions and radiosensitivity in zebrafish. Together, our findings provide novel insights into the connection of radiation injuries with temperature alterations in fish, and suggest that maintaining the stability of gram-positive bacteria may be efficacious to protect aquatic organisms against short or long-term radioactive contamination in the context of global climate change.