Involvement of the gut microbiota in the metabolic phenotypes of two sympatric gerbils.

Temporal niche partitioning is a crucial strategy for sympatric species to avoid predation and competition for habitat space and food resources. This study investigated the effect of the gut microbiota on the metabolic rhythms of two sympatric gerbil species (Meriones unguiculatus and Meriones meridianus) to test the hypothesis that the oscillatory patterns of microbiota may not fully mirror those of the host's metabolism. Experiment 1 compared the circadian metabolic and gut microbiota rhythms of M. unguiculatus (n = 12) and M. meridianus (n = 12) and measured the subjects' body temperatures and environmental temperature preferences. In Experiment 2.1, six M. meridianus gerbils were treated with antibiotics, and in Experiment 2.2, 21 M. unguiculatus gerbils (seven per treatment) were randomly gavaged with saline or a gut microbiota suspension from either M. unguiculatus or M. meridianus; their metabolic rhythms were subsequently measured. The results showed that the two gerbils had different metabolic phenotypes that determined activity heterogeneity and contributed to their coexistence. The relative abundances of Bacteroidetes, Actinobacteria, and Cyanobacteria in M. meridianus varied rhythmically in parallel with the daily metabolic rate, which was significantly higher at night than during the day. The rhythm of the metabolic rate was not noticeable in M. unguiculatus. However, in M.unguiculatus, the relative abundances of Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia were significantly higher during the day than at night, while Cyanobacteria exhibited the opposite pattern. Antibiotic treatment significantly weakened the metabolic rhythms of M. meridianus, and the circadian rhythms slowly recovered after stopping antibiotic gavage. However, after transplanting M. meridianus' gut microbiota into M. unguiculatus, the metabolic rate of M. unguiculatus was not significantly different from that of the control groups. Our hypothesis was partly supported: the microbiota was only partially involved in regulating the metabolic rhythms of gerbils, and other factors could compensate for the effect of the gut microbiota on host metabolic rhythms. This finding underscores the complexity of host-microbiota interactions and highlights the need for further exploration into the multifaceted mechanisms governing host metabolic regulation.

Thermo-TRPs and gut microbiota are involved in thermogenesis and energy metabolism during low temperature exposure of obese mice.

Ambient temperature and food composition can affect energy metabolism of the host. Thermal transient receptor potential ion channels (thermo-TRPs) can detect temperature signals and are involved in the regulation of thermogenesis and energy homeostasis. Further, the gut microbiota have also been implicated in thermogenesis and obesity. In the present study, we tested the hypothesis that thermo-TRPs and gut microbiota are involved in reducing diet-induced obesity (DIO) during low temperature exposure. C57BL/6J mice in obese (body mass gain >45%), lean (body mass gain <15%) and control (body mass gain <1%) groups were exposed to high (23±1°C) or low (4±1°C) ambient temperature for 28 days. Our data showed that low temperature exposure attenuated DIO, but enhanced brown adipose tissue (BAT) thermogenesis. Low temperature exposure also resulted in increased noradrenaline (NA) concentrations in the hypothalamus, decreased TRP melastatin 8 (TRPM8) expression in the small intestine, and altered composition and diversity of gut microbiota. In DIO mice, there was a decrease in overall energy intake along with a reduction in TRP ankyrin 1 (TRPA1) expression and an increase in NA concentration in the small intestine. DIO mice also showed increases in Oscillospira, [Ruminococcus], Lactococcus and Christensenella and decreases in Prevotella, Odoribacter and Lactobacillus at the genus level in fecal samples. Together, our data suggest that thermos-TRPs and gut microbiota are involved in thermogenesis and energy metabolism during low temperature exposure in DIO mice.

The interaction between gut microbiota and hibernation in mammals.

Hibernation, an evolved survival trait among animals, enables them to endure frigid temperatures and food scarcity during the winter months, and it is a widespread phenomenon observed in mammals. The gut microbiota, a crucial component of animal nutrition and health, exhibits particularly dynamic interactions in hibernating mammals. This manuscript comprehensively evaluates the impacts of fasting, hypothermia, and hypometabolism on the gut microbiota of hibernating mammals. It suggests that alterations in the gut microbiota may contribute significantly to the maintenance of energy metabolism and intestinal immune function during hibernation, mediated by their metabolites. By delving into these intricacies, we can gain a deeper understanding of how hibernating mammals adapt to their environments and the consequences of dietary modifications on the symbiotic relationship between the gut microbiota and the host. Additionally, this knowledge can inform our comprehension of the protective mechanisms underlying long-term fasting in non-hibernating species, including humans, providing valuable insights into nutritional strategies and health maintenance.

The Impact of High-Temperature Stress on Gut Microbiota and Reproduction in Siberian Hamsters (Phodopus sungorus).

Global warming has induced alterations in the grassland ecosystem, such as elevated temperatures and decreased precipitation, which disturb the equilibrium of these ecosystems and impact various physiological processes of grassland rodents, encompassing growth, development, and reproduction. As global warming intensifies, the repercussions of high-temperature stress on small mammals are garnering increased attention. Recently, research has highlighted that the composition and ratio of gut microbiota are not only shaped by environmental factors and the host itself but also reciprocally influence an array of physiological functions and energy metabolism in animals. In this research, we combined 16S rRNA high-throughput sequencing with conventional physiological assessments, to elucidate the consequences of high-temperature stress on the gut microbiota structure and reproductive capacity of Siberian hamsters (Phodopus sungorus). The results were as follows: 1. The growth and development of male and female hamsters in the high-temperature group were delayed, with lower body weight and reduced food intake. 2. High temperature inhibits the development of reproductive organs in both female and male hamsters. 3. High temperature changes the composition and proportion of gut microbiota, reducing bacteria that promote reproduction, such as Pseudobutyricoccus, Ruminiclostridium-E, Sporofaciens, UMGS1071, and CAG_353. Consequently, our study elucidates the specific impacts of high-temperature stress on the gut microbiota dynamics and reproductive health of Siberian hamsters, thereby furnishing insights for managing rodent populations amidst global climatic shifts. It also offers a valuable framework for understanding seasonal variations in mammalian reproductive strategies, contributing to the broader discourse on conservation and adaptation under changing environmental conditions.

Comparison of distinct gut bacterial communities in different stage of prediapause and nondiapause larvae in Loxostege sticticalis.

Introduction: Symbiotic microorganisms in insects regulate multiple physiological functions, widely participating in nutrient metabolism, immune regulation, and crucial regulatory roles in development. However, little is known about how microbial factors might respond to the preparation of insect diapause. Methods: The gut bacterial communities of Loxostege sticticalis larvae induced at different photoperiod of long (LD16:8, nondiapause) and short (LD12:12, prediapause) daylength were compared, by 16S rRNA Illumina MiSeq. Results: A total number of 42 phylum, 78 classes, 191 orders, 286 families, 495 genera, and 424 species were identified in the intestinal bacterial community of L. sticticalis larvae. Alpha diversity and beta diversity analyses revealed significant differences between nondiapause and prediapause larvae. In non-diapause larvae, the dominant intestinal bacteria were Firmicutes and Proteobacteria. In specific, in 3rd and 4th instar larvae, the main intestinal bacteria were Staphylococcus, while in 5th instar, it was JC017. For the prediapause larvae, the dominant phylum in 3rd instar larvae was Firmicutes, with the dominant genus of Staphylococcus, while in 4th and 5th instar larvae was Bacteroidota, with the dominant genus 4th instar was Staphylococcus, and in 5th instar was JC017. KEGG functional prediction analysis revealed that functional bacterial groups involved in metabolism had the highest abundance values. Specifically, the amino acid metabolism of metabolism-related functional genes in the 3rd instar prediapause larvae was significantly lower than that in the 4th and 5th instar prediapause larvae and the non-diapause treatment. However, the carbohydrate metabolism in 3rd instar prediapause larvae was significantly higher than that in 4th and 5th instar prediapause larvae and non-diapause treatments. The dominant bacterial phylum in the prediapause larvae at different stages of L. sticticalis was varied, and there were significant differences in community diversity and richness. Discussion: These results suggest a complex interaction between the hosts' physiological state and its gut microbiota, indicating that bacterial communities may assist insects in adapting to diapause preparation by regulating their metabolic levels. This study lays the foundation for further understanding the physiological mechanisms by which intestinal microorganisms regulate overwintering dormancy in the L. sticticalis.

Role of gut microbiota in the postnatal thermoregulation of Brandt's voles.

Homeothermy is crucial for mammals. Postnatal growth is the key period for young offspring to acquire gut microbiota. Although gut microbiota may affect mammal thermogenesis, the impact of developmental regulation of gut microbiota on the ability of young pups to produce heat remains unclear. Antibiotics were used to interfere with the establishment of gut microbiota during the development of Brandt's voles, and their thermogenic development and regulatory pathways were determined. Deprivation of microbiota by antibiotics inhibits the development of thermogenesis in pups. Butyric acid and bile acid, as metabolites of gut microbiota, participated in the thermoregulation of pups. We propose that gut microbiota promote the development of thermoregulation through the butyric acid-free fatty acid receptor-2-uncoupling protein-1 or the deoxycholic acid-Takeda-G-protein-receptor-5-uncoupling protein-1 pathway in pups. These results show a relationship between gut microbiota and thermogenesis and expand the mechanism of postnatal development of thermogenesis in small mammals.

Mechanism of inulin in colic and gut microbiota of captive Asian elephant.

BACKGROUND: Gut microbiota have a complex role on the survivability, digestive physiology, production, and growth performance in animals. Recent studies have emphasized the effects of prebiotics therapy on the gut disease, but the relationship between elephant gut-related diseases and prebiotics remains elusive. Here, a case study was undertaken to evaluate the mechanism of inulin treatment in colic in Asian elephant (Elephas maximus Linnaeus). METHODS: Fecal samples were collected from a sick elephant and four healthy elephants. Analysis of microbial profile was carried out by 16S rRNA sequencing, and the short chain fatty acids were tested by gas chromatography. The physiological function of "inulin-microbiota" of elephant was verified in mice by fecal microbial transplantation (FMT). The expression of related proteins was determined by Western blotting and qPCR. RESULTS: (1) Eating inulin can cure gut colic of the sick elephant and changed gut microbiota. (2) It was found that "inulin microbiota" from the post-treatment elephants can promote the proliferation of intestinal cells, increase the utilization of short chain fatty acids (SCFAs), maintain intestinal barrier, and reduce the inflammation in mice. (3) The mechanism was inulin-gut microbiota-SCFAs-immune barrier. CONCLUSIONS: Inulin contributed to rehabilitate the gut microbiota and gut immune barrier of the elephant with colic. This provides reasonable verification for using prebiotics to treat the colic in captive elephants. Prebiotics will foresure play an increasingly important role in disease prevention and treatment of captive animals in the future. Video Abstract.

Role of transient receptor potential vanilloid-1 in behavioral thermoregulation of the Mongolian gerbil Meriones unguiculatus.

Ambient temperature considerably affects the physiology and behavior of mammals. Thermosensory and thermoregulatory abilities play an important role in the response to changing ambient temperature in endotherms. However, the molecular mechanisms of behavioral thermoregulation remain poorly understood. Transient receptor potential vanilloid-1 (TRPV1) is activated by changes in ambient temperature and is involved in acute thermoregulation. Here, we aimed to determine whether TRPV1 is involved in behavioral thermoregulation in wild rodents by conducting 2 experiments. In the first, 42 adult Mongolian gerbils (Meriones unguiculatus; 14 per treatment) were randomly assigned to 3 housing temperatures (4, 23, and 36°C) for 4 weeks. In the second, 20 gerbils (10 per treatment) were randomly injected with capsaicin (TRPV1 agonist) or AMG517 (TRPV1 antagonist). The results showed a significant decrease in food intake and non-shivering thermogenesis in the gerbils housed at 36°C. Additionally, there was a significant increase in the preference of gerbils housed at 4°C to low temperatures. The expression of TRPV1 protein in the brown adipose tissue (BAT) and liver was significantly positively correlated with that of protein kinase A (PKA). The expression of TRPV1 and PKA proteins in the BAT was positively correlated with the temperature preference of the gerbils. The gerbils injected with capsaicin preferred significantly lower temperatures than the control group gerbils. These findings suggest that TRPV1 and PKA are involved in behavioral thermoregulation in Mongolian gerbils.

The Gut Microbiota May Affect Personality in Mongolian Gerbils.

The "gut-microbiota-brain axis" reveals that gut microbiota plays a critical role in the orchestrating behavior of the host. However, the correlation between the host personalities and the gut microbiota is still rarely known. To investigate whether the gut microbiota of Mongolian gerbils (Meriones unguiculatus) differs between bold and shy personalities, we compared the gut microbiota of bold and shy gerbils, and then we transplanted the gut microbiota of bold and shy gerbils into middle group gerbils (individuals with less bold and shy personalities). We found a significant overall correlation between host boldness and gut microbiota. Even though there were no significant differences in alpha diversity and beta diversity of gut microbiota between bold and shy gerbils, the Firmicutes/Bacteroidetes phyla and Odoribacter and Blautia genus were higher in bold gerbils, and Escherichia_shigella genus was lower. Furthermore, the fecal microbiota transplantation showed that changes in gut microbiota could not evidently cause the increase or decrease in the gerbil's boldness score, but it increased the part of boldness behaviors by gavaging the "bold fecal microbiota". Overall, these data demonstrated that gut microbiota were significantly correlated with the personalities of the hosts, and alteration of microbiota could alter host boldness to a certain extent.

Effects of High-Fat Diet During Childhood on Precocious Puberty and Gut Microbiota in Mice.

Precocious puberty mostly stems from endocrine disorders. However, more and more studies show that a high-fat diet (HFD) is closely related to precocious puberty, but its mechanism is unknown. Since gut microbiota is associated with hormone secretion and obesity, it inspires us to detect the mechanism of gut microbiota in triggering precocious puberty. The model of precocious puberty was established by feeding female mice with an HFD from 21 days old. After puberty, the serum hormone levels, gut microbiome sequencing, and metabolomics were collected. DNA was extracted from feces, and the V3-V4 region of the bacterial 16S rRNA gene was amplified, followed by microbial composition analysis. Subsequently, associations between precocious puberty and the microbiota were determined. We found that (1) HFD after weaning caused precocious puberty, increased serum estradiol, leptin, deoxycholic acid (DCA), and gonadotropin-releasing hormone (GnRH) in the hypothalamus; (2) Through correlation analysis, we found that GnRH was positively correlated with Desulfovibrio, Lachnoclostridium, GCA-900066575, Streptococcus, Anaerotruncus, and Bifidobacterium, suggesting that these bacteria may have a role in promoting sexual development. (3) "HFD-microbiota" transplantation promoted the precocious puberty of mice. (4) Estrogen changes the composition and proportion of gut microbiota and promotes precocious puberty. Therefore, the effect of HFD on precocious puberty is regulated by the interaction of gut microbiota and hormones.

Incomplete Concordance Between Host Phylogeny and Gut Microbial Community in Tibetan Wetland Birds.

Gut microbial communities of animals play key roles in host evolution, while the relationship between gut microbiota and host evolution in Tibetan birds remains unknown. Herein, we sequenced the gut microbiota of 67 wild birds of seven species dwelling in the Tibetan wetlands. We found an obvious species-specific structure of gut microbiota among these plateau birds whose habitats were overlapped. Different from plateau mammals, there was no strict synergy between the hierarchical tree of gut microbial community and species phylogeny. In brown-headed gulls (Larus brunnicephalus) as an example, the structure of gut microbiota differed in different habitats, and the relative abundance of bacteria, such as Lactobacillus, Streptococcus, Paracoccus, Lachnospiraceae, and Vibrio, significantly correlated with altitude. Finally, we found various pathogenic bacteria in the birds of these plateau wetlands, and the interspecific differences were related to their diet and living environments.

Stabilization and optimization of host-microbe-environment interactions as a potential reason for the behavior of natal philopatry.

Many animals engage in a behavior known as natal philopatry, where after sexual maturity they return to their own birthplaces for subsequent reproduction. There are many proposed ultimate factors that may underlie the evolution of natal philopatry, such as genetic optimization, suitable living conditions, and friendly neighbors, which can improve the survival rates of offspring. However, here we propose that a key factor that has been overlooked could be the colonization of gut microbiota during early life and the effects these microorganisms have on host performance and fitness. In addition to the bacteria transmitted from the mother to offspring, microbes from the surrounding environment also account for a large proportion of the developing gut microbiome. While it was long believed that microbial species all have global distributions, we now know that there are substantial geographic differences and dispersal limitations to environmental microbes. The establishment of gut microbiota during early life has enormous impacts on animal development, including energy metabolism, training of the immune system, and cognitive development. Moreover, these microbial effects scale to influence animal performance and fitness, raising the possibility for natural selection to act on the integrated combination of gut microbial communities and host genetics (i.e. the holobiont). Therefore, in this paper, we propose a hypothesis: that optimization of host-microbe-environment interactions represents a potentially important yet overlooked reason for natal philopatry. Microbiota obtained by natal philopatry could help animals adapt to the environment and improve the survival rates of their young. We propose future directions to test these ideas, and the implications that this hypothesis has for our understanding of host-microbe interactions.

Influence of HFD-induced precocious puberty on neurodevelopment in mice.

BACKGROUND: Precocious puberty is frequently associated with obesity, which will lead to long-term effects, especially on growth and reproduction. However, the effect of precocious puberty on children's neurodevelopment is still unknown. OBJECTIVES: Here we evaluated the effect of High fat diet (HFD)-induced precocious puberty on neurodevelopment and behaviors of animals. METHODS: Ovaries sections were stained with hematoxylin-eosin (H&E) using standard techniques. Behavioral tests included elevated plus maze (EPM), open field exploration, Y-Maze, marble burying test, and novelty- suppressed feeding. The expression of genes related to puberty and neural development was detected by immunohistochemistry and Western blot. RESULTS: Our results showed HFD-induced precocious puberty increased the risk-taking behavior and decreased memory of mice. The content of Tyrosine hydroxylase (TH) and Arginine vasopressin (AVP) in hypothalamus were higher in HFD group than control group. Although the recovery of normal diet will gradually restore the body fat and other physiological index of mice, the anxiety increases in adult mice, and the memory is also damaged. CONCLUSIONS: These findings describe the sensitivity of mice brain to HFD-induced precocious puberty and the irrecoverability of neural damage caused by precocious puberty. Therefore, avoiding HFD in childhood is important to prevent precocious puberty and neurodevelopmental impairment in mice.

Coprophagy prevention alters microbiome, metabolism, neurochemistry, and cognitive behavior in a small mammal.

Many small mammals engage in coprophagy, or the behavior of consuming feces, as a means to meet nutritional requirements when feeding on low-quality foods. In addition to nutritional benefits, coprophagy may also help herbivores retain necessary gut microbial diversity and function, which may have downstream physiological effects, such as maintaining energy balance and cognitive function. Here, we used collars to prevent Brandt's vole (Lasiopodomys brandtii) from engaging in coprophagy and monitored changes in microbial community structure, energy metabolism, and cognitive performance. In this research, we found that coprophagy prevention decreased alpha diversity of the gut microbiota, and altered proportions of microbial taxa such as Bacteroidetes, Firmicutes, and Oscillospira. Preventing coprophagy resulted in a reduced body mass, and increased food intake. Importantly, coprophagy prevention decreased vole cognitive behavior and altered levels of neurotransmitters in brain. Daily acetate administration was able to reverse some of the coprophagy prevention-induced changes in microbiota composition, metabolism, neurochemistry, and cognitive behavior. These findings identify the functional importance of coprophagy behavior and interactions between the gut microbiota, energy metabolism, and neurological function. Our results suggest that coprophagy contributes to stabilizing the gut microbiota, promoting microbial metabolism, maintaining host energy balance and, consequently, altering cognitive performance.

Bifidobacterium pseudolongum reduces triglycerides by modulating gut microbiota in mice fed high-fat food.

Obesity has become a growing concern around the world. The purpose of this study was to investigate the potential benefit of Bifidobacterium pseudolongum (B. pseudolongum) on obesity, gut microbiota, and its physiological mechanism. The obese mice model was established with a high-fat diet (HFD), and the treatment were used the strain B. pseudolongum. We investigated the changes in fat content, plasma metabolites and gut microbiota on obese mice and B. pseudolongum treated obese mice. We found that B. pseudolongum treatment significantly decreased the body mass (about 12 %), plasma triglycerides (about 12.4 %), gross energy intake (about 12.8 %), and visceral fat (about 26.5 %) in obese mice. Further, High-throughput pyrosequencing of the 16S rRNA demonstrated that B. pseudolongum treatment markedly recovered the gut microbiota dysbiosis in obese mice, including the diversity of microbiota and the ratio of Firmicutes to Bacteroidetes. B. pseudolongum treatment increased the abundance of the bacterial genus Butyricimonas and Bifidobacterium. Therefore, B. pseudolongum may have therapeutic potential for the treatment of diet-induced obesity (DIO). B. pseudolongum treatment could change host gut microbiota and provide benefits to host digestive processes that mitigate metabolic diseases.

The microbiota-gut-brain interaction in regulating host metabolic adaptation to cold in male Brandt's voles (Lasiopodomys brandtii).

Gut microbiota play a critical role in orchestrating metabolic homeostasis of the host. However, the crosstalk between host and microbial symbionts in small mammals are rarely illustrated. We used male Brandt's voles (Lasiopodomys brandtii) to test the hypothesis that gut microbiota and host neurotransmitters, such as norepinephrine (NE), interact to regulate energetics and thermogenesis during cold acclimation. We found that increases in food intake and thermogenesis were associated with increased monoamine neurotransmitters, ghrelin, short-chain fatty acids, and altered cecal microbiota during cold acclimation. Further, our pair-fed study showed that cold temperature can alter the cecal microbiota independently of overfeeding. Using cecal microbiota transplant along with ß3-adrenoceptor antagonism and PKA inhibition, we confirmed that transplant of cold-acclimated microbiota increased thermogenesis through activation of cAMP-PKA-pCREB signaling. In addition, NE manipulation induced a long-term alteration in gut microbiota structure. These data demonstrate that gut microbiota-NE crosstalk via cAMP signaling regulates energetics and thermogenesis during cold acclimation in male Brandt's voles.

Elevation is Associated with Human Skin Microbiomes.

Human skin microbiota plays a crucial role in the defense against pathogens, and is associated with various skin diseases. High elevation is positively correlated with various extreme environmental conditions (i.e., high ultraviolet radiation), which may exert selection pressure on skin microbiota, and therefore influence human health. Most studies regarding skin microbial communities have focused on low-elevation hosts. Few studies have explored skin microbiota in high-elevation humans. Here, we investigated the diversity, function, assembly, and co-occurrence patterns of skin microbiotas from 35 health human subjects across three body sites (forehead, opisthenar, and palm) and seven elevation gradients from 501 to 3431 m. Alpha diversity values (i.e., Shannon diversity and observed operational taxonomic units (OTUs)) decreased with increasing elevation regardless of the body site, while beta diversity (Jaccard and Bray-Curtis dissimilarities) showed an increasing trend with elevation. Elevation is a significant factor that influences human skin microbiota, even after controlling host-related factors. Skin microbiotas at high elevation with more than 3000 m on the Qinghai-Tibet Plateau, had a significant structural or functional separation from those at low elevation with less than 3000 m. Notably, the clustering coefficient, average degree, and network density were all lower at high-elevation than those at low-elevation, suggesting that high-elevation skin networks were more fragile and less connected. Phylogenetic analysis showed that human skin microbiotas are mainly dominated by stochastic processes (58.4%-74.6%), but skin microbiotas at high-elevation harbor a greater portion of deterministic processes than those at low-elevation, indicating that high-elevation may be conducive to the promotion of deterministic processes. Our results reveal that the filtering and selection of the changeable high-elevation environment on the Qinghai-Tibet Plateau may lead to less stable skin microbial community structures.

Correction to: Huddling remodels gut microbiota to reduce energy requirements in a small mammal species during cold exposure.

Following publication of the original article [1], the authors reported an error in the caption of Fig. 4.

Huddling remodels gut microbiota to reduce energy requirements in a small mammal species during cold exposure.

BACKGROUND: Huddling is highly evolved as a cooperative behavioral strategy for social mammals to maximize their fitness in harsh environments. Huddling behavior can change psychological and physiological responses. The coevolution of mammals with their microbial communities confers fitness benefits to both partners. The gut microbiome is a key regulator of host immune and metabolic functions. We hypothesized that huddling behavior altered energetics and thermoregulation by shaping caecal microbiota in small herbivores. Brandt's voles (Lasiopodomys brandtii) were maintained in a group (huddling) or as individuals (separated) and were exposed to warm (23 ± 1 °C) and cold (4 ± 1 °C) air temperatures (Ta). RESULTS: Voles exposed to cold Ta had higher energy intake, resting metabolic rate (RMR) and nonshivering thermogenesis (NST) than voles exposed to warm Ta. Huddling voles had lower RMR and NST than separated voles in cold. In addition, huddling voles had a higher surface body temperature (Tsurface), but lower core body temperature (Tcore) than separated voles, suggesting a lower set-point of Tcore in huddling voles. Both cold and huddling induced a marked variation in caecal bacterial composition, which was associated with the lower Tcore. Huddling voles had a higher α and ß-diversity, abundance of Lachnospiraceae and Veillonellaceae, but lower abundance of Cyanobacteria, Tenericutes, TM7, Comamonadaceae, and Sinobacteraceae than separated voles. Huddling or cold resulted in higher concentrations of short-chain fatty acids (SCFAs), particularly acetic acid and butyric acid when compared to their counterparts. Transplantation of caecal microbiota from cold-separated voles but not from cold-huddling voles induced significant increases in energy intake and RMR compared to that from warm-separated voles. CONCLUSIONS: These findings demonstrate that the remodeling of gut microbiota, which is associated with a reduction in host Tcore, mediates cold- and huddling-induced energy intake and thermoregulation and therefore orchestrates host metabolic and thermal homeostasis. It highlights the coevolutionary mechanism of host huddling and gut microbiota in thermoregulation and energy saving for winter survival in endotherms.