Effects of host identity on the gut microbiota: A comparative study on three microtinae species.

BACKGROUND: Gut microbiota exert an immense effect on host health and host environmental adaptation. Furthermore, the composition and structure of gut microbiota are determined by the environment and host genetic factors. However, the relative contribution of the environment and host genetic factors toward shaping the structure of gut microbiota has been poorly understood. METHODS: In this study, we characterized the fecal microbial communities of the closely related voles Neodon fuscus, Lasiopodomys brandtii, and L. mandarinus after caged feeding in the laboratory for 6 months, through high-throughput sequencing and bioinformatics analysis. RESULTS: The results of pairwise comparisons of N. fuscus vs. L. brandtii and L. mandarinus vs. L. brandtii revealed significant differences in bacterial diversity and composition after domestication. While 991 same operational taxonomic units (OTUs) were shared in three voles, there were 362, 291, and 303 species-specific OTUs in N. fuscus, L. brandtii, and L. mandarinus, respectively. The relative abundances of Proteobacteria and Prevotella, which are reported to be enriched in high-altitude populations, were significantly higher in high-altitude N. fuscus than in low-altitude L. brandtii after domestication. Firmicutes, which produce various digestive enzymes for energy metabolism, and Spirochaetes, which can degrade cellulose, were found in higher abundance in subterranean L. mandarinus than that in L. brandtii which dwells on the earth surface. CONCLUSION: Our findings showed that some components of gut microbiota still maintained dominance even when different host species are reared under the same environmental conditions, suggesting that these bacteria are substantially influenced by host factors.

Zoonotic Potential of Brucella microti.

Background: Brucella microti is a pathogen of rodents and wild mammals. Here, we report the first probable infection with B. microti in a mammalogist. Materials and Methods: In the study, we provided complete clinical description as well as laboratory analysis of probable human infection caused by B. microti. Results: Considering the clinical course of the infection, the obvious epidemiological link (a bite by an infected rodent), the isolation of a pathogen from a sick vole that was affected by clinical infection with B. microti, and the specific serological response (slow agglutination test) in human patient, we can conclude that the human disease described here was probably caused by B. microti, an emerging bacterial pathogen transmitted by rodents. Conclusion: Rodents and other wildlife need to be monitored not only for established zoonotic agents such as hantaviruses, lymphocytic choriomeningitis virus, Leptospira spp., Francisella tularensis, but also for Brucella microti and other atypical rodent-borne brucellae.

Co-infections mask pathogen-specific associations with the gut microbiota in wild voles.

Research Highlight: Brila, I., Lavirinienko, A., Tukalenko, E., Kallio, E. R., Mappes, T. & Watts, P. C. (2022). Idiosyncratic effects of coinfection on the association between systemic pathogens and the gut microbiota of a wild rodent, the bank vole (Myodes glareolus). Journal of Animal Ecology, https://besjournals.onlinelibrary.wiley.com/doi/10.1111/1365-2656.13869. Interactions between pathogens and host-associated microbial communities can influence host fitness, disease progression and pathogen emergence. The vast majority of studies characterize interactions between single pathogens and bacterial commensals, yet co-infections with multiple pathogens are the norm in nature. In their paper on pathogen-microbiome interactions, Brila et al. (2022) examine how co-infections with four systemic pathogens associate with the gut microbiota in wild bank voles. Building on a series of tests, the authors show that excluding co-infection information from statistical models masks pathogen-specific patterns and confounds interpretations. This paper advances on previous studies by generating surveillance data on a phylogenetically diverse suite of vole pathogens to address the question as to whether pathogens exhibit unique or universal associations with gut commensals. They report that even bacterial pathogens with similar transmission ecology have divergent associations with gut microbes, and highlight that a mechanistic understanding of host-pathogen interactions is necessary for decoding the diverse consequences for gut microbial communities.

Idiosyncratic effects of coinfection on the association between systemic pathogens and the gut microbiota of a wild rodent, the bank vole Myodes glareolus.

The effects of systemic pathogens on gut microbiota of wild animals are poorly understood. Furthermore, coinfections are the norm in nature, yet most studies of pathogen-microbiota interactions focus on effects of single pathogen infections on gut microbiota. We examined the effects of four systemic pathogens (bacteria Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato, apicomplexan protozoa Babesia microti and Puumala orthohantavirus) and coinfections among them on the (bacterial) gut microbiota of wild bank voles Myodes glareolus. We hypothesized that: (1) the effects of coinfection on gut microbiota generally differ from those of a single pathogen infection, (2) systemic pathogens have individual (i.e. distinct) associations with gut microbiota, which are modified by coinfection and (3) the effects of coinfection (compared with those of single infection) are idiosyncratic (i.e. pathogen-specific). The gut microbiota of coinfected bank voles differed from that of single pathogen infected individuals, although, as predicted, the effects of coinfections were unique for each pathogen. After accounting for coinfections, only Puumala orthohantavirus was associated with higher α-diversity; however, all pathogens affected gut microbiota ß-diversity in a pathogen-specific way, affecting both rare and abundant gut bacteria. Our results showed that the effects of systemic pathogens on host's gut microbiota vary depending on the pathogen species, resulting in idiosyncratic signatures of coinfection. Furthermore, our results emphasize that neglecting the impact of coinfections can mask patterns of pathogen-microbiota associations.

Investigation on haplotypes of ixodid ticks and retrospective finding of Borrelia miyamotoi in bank vole (Myodes glareolus) in Switzerland.

The current status of tick species, important tick-borne bacteria and protozoan parasites is well-documented in Switzerland. However, reports on the genetic diversity and geographical relationships of tick species in this country appear to be in part lacking or outdated. Thus, the aim of this study was to collect ticks from various host species in southern Switzerland, to compare them in a geographical context and to screen in these samples rare tick-borne pathogens hitherto not reported or having low prevalence in Switzerland. In 2019-2020 altogether 177 ixodid ticks were collected from the vegetation, as well as from humans (n = 17), dogs (n = 23), cats (n = 41), red deer (n = 8), a European rabbit and a European hedgehog at 25 locations in three cantons of south Switzerland. Tick species were identified morphologically, followed by DNA extraction and comparison of mitochondrial haplotypes with molecular-phylogenetic methods. Tick DNA extracts, as well as sixty-two rodent liver or spleen tissue DNA extracts (representing six species) available from 2005 to 2006 were screened for trypanosomes, Occidentia massiliensis and Borrelia miyamotoi. Morphologically, three tick species were identified: Ixodes ricinus (n = 170), Rhipicephalus sanguineus sensu lato (n = 6) and I. hexagonus (n = 1). In contrast to companion animals (dogs, cats) immature ticks (larvae and nymphs) predominated on humans, which was a highly significant association (P < 0.0001). Molecular comparison of the cytochrome c oxidase subunit I (cox1) gene with GenBank data established the species as R. sanguineus sensu stricto and confirmed I. hexagonus, both showing 99.8-100% sequence identity to conspecific ticks from northern Italy. Seventy-nine specimens morphologically identified as I. ricinus revealed high 16S rRNA gene haplotype diversity and represented two phylogenetic groups. Two I. ricinus haplotypes from Switzerland belonged to the same haplogroup with I. inopinatus from Spain, Germany and Austria as well as with I. ricinus reported from a broad geographical range of Europe (including Italy, the Netherlands, Poland, Latvia and Sweden). All 141 tick DNA extracts (from five R. sanguineus s.l., 135 I. ricinus and one I. hexagonus) and 62 rodent tissue DNA extracts were negative for trypanosomes and O. massiliensis. However, B. miyamotoi was identified in a bank vole (Myodes glareolus) and three ticks by sequencing. From Switzerland, this is the first report of tick haplotypes that are phylogenetically closely related to I. inopinatus. However, based on their morphology, both specimens are considered as I. ricinus. These results highlight the importance that the identification of I. inopinatus should be based on coherent morphologic and molecular properties. This is also the first report of rodent-borne B. miyamotoi in Switzerland. Taking into account the year of collection (2005), in a chronological order this might be the first indication of B. miyamotoi in any rodent species in Europe.

Surveillance for diseases, pathogens, and toxicants of muskrat (Ondatra zibethicus) in Pennsylvania and surrounding regions.

Using diagnostic data and contemporary sampling efforts, we conducted surveillance for a diversity of pathogens, toxicants, and diseases of muskrats (Ondatra zibethicus). Between 1977 and 2019, 26 diagnostic cases were examined from Kansas and throughout the Southeast and Mid-Atlantic, USA. We identified multiple causes of mortality in muskrats, but trauma (8/26), Tyzzer's disease (5/6), and cysticercosis (5/26) were the most common. We also conducted necropsies, during November 2018-January 2019 Pennsylvania muskrat trapping season, on 380 trapper-harvested muskrat carcasses after the pelt was removed. Tissue samples and exudate were tested for presence of or exposure to a suite of pathogens and contaminants. Gastrointestinal tracts were examined for helminths. Intestinal helminths were present in 39.2% of necropsied muskrats, with Hymenolepis spp. (62%) and echinostome spp. (44%) being the most common Molecular testing identified a low prevalence of infection with Clostridium piliforme in the feces and Sarcocystis spp. in the heart. We detected a low seroprevalence to Toxoplasma gondii (1/380). No muskrats were positive for Francisella tularensis or Babesia spp. Cysticercosis was detected in 20% (5/26) of diagnostic cases and 15% (57/380) of our trapper-harvested muskrats. Toxic concentrations of arsenic, cadmium, lead, or mercury were not detected in tested liver samples. Copper, molybdenum, and zinc concentrations were detected at acceptable levels comparative to previous studies. Parasite intensity and abundance were typical of historic reports; however, younger muskrats had higher intensity of infection than older muskrats which is contradictory to what has been previously reported. A diversity of pathogens and contaminants have been reported from muskrats, but the associated disease impacts are poorly understood. Our data are consistent with historic reports and highlight the wide range of parasites, pathogens and contaminants harbored by muskrats in Pennsylvania. The data collected are a critical component in assessing overall muskrat health and serve as a basis for understanding the impacts of disease on recent muskrat population declines.

Borrelia Infection in Bank Voles Myodes glareolus Is Associated With Specific DQB Haplotypes Which Affect Allelic Divergence Within Individuals.

The high polymorphism of Major Histocompatibility Complex (MHC) genes is generally considered to be a result of pathogen-mediated balancing selection. Such selection may operate in the form of heterozygote advantage, and/or through specific MHC allele-pathogen interactions. Specific MHC allele-pathogen interactions may promote polymorphism via negative frequency-dependent selection (NFDS), or selection that varies in time and/or space because of variability in the composition of the pathogen community (fluctuating selection; FS). In addition, divergent allele advantage (DAA) may act on top of these forms of balancing selection, explaining the high sequence divergence between MHC alleles. DAA has primarily been thought of as an extension of heterozygote advantage. However, DAA could also work in concert with NFDS though this is yet to be tested explicitly. To evaluate the importance of DAA in pathogen-mediated balancing selection, we surveyed allelic polymorphism of MHC class II DQB genes in wild bank voles (Myodes glareolus) and tested for associations between DQB haplotypes and infection by Borrelia afzelii, a tick-transmitted bacterium causing Lyme disease in humans. We found two significant associations between DQB haplotypes and infection status: one haplotype was associated with lower risk of infection (resistance), while another was associated with higher risk of infection (susceptibility). Interestingly, allelic divergence within individuals was higher for voles with the resistance haplotype compared to other voles. In contrast, allelic divergence was lower for voles with the susceptibility haplotype than other voles. The pattern of higher allelic divergence in individuals with the resistance haplotype is consistent with NFDS favouring divergent alleles in a natural population, hence selection where DAA works in concert with NFDS.

Rodent host population dynamics drive zoonotic Lyme Borreliosis and Orthohantavirus infections in humans in Northern Europe.

Zoonotic diseases, caused by pathogens transmitted between other vertebrate animals and humans, pose a major risk to human health. Rodents are important reservoir hosts for many zoonotic pathogens, and rodent population dynamics affect the infection dynamics of rodent-borne diseases, such as diseases caused by hantaviruses. However, the role of rodent population dynamics in determining the infection dynamics of rodent-associated tick-borne diseases, such as Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato bacteria, have gained limited attention in Northern Europe, despite the multiannual abundance fluctuations, the so-called vole cycles, that characterise rodent population dynamics in the region. Here, we quantify the associations between rodent abundance and LB human cases and Puumala Orthohantavirus (PUUV) infections by using two time series (25-year and 9-year) in Finland. Both bank vole (Myodes glareolus) abundance as well as LB and PUUV infection incidence in humans showed approximately 3-year cycles. Without vector transmitted PUUV infections followed the bank vole host abundance fluctuations with two-month time lag, whereas tick-transmitted LB was associated with bank vole abundance ca. 12 and 24 months earlier. However, the strength of association between LB incidence and bank vole abundance ca. 12 months before varied over the study years. This study highlights that the human risk to acquire rodent-borne pathogens, as well as rodent-associated tick-borne pathogens is associated with the vole cycles in Northern Fennoscandia, yet with complex time lags.

Hantavirus-Leptospira coinfections in small mammals from central Germany.

European orthohantaviruses (Puumala orthohantavirus (PUUV); Dobrava-Belgrade orthohantavirus (DOBV), genotype Kurkino; Tula orthohantavirus (TULV)), and Leptospira spp. are small mammal-associated zoonotic pathogens that cause diseases with potentially similar symptoms in humans. We investigated the frequency of Leptospira spp. and hantavirus single and double infections in small mammals from 22 sites in Thuringia, central Germany, during 2017. TULV infections were detected at 18 of 22 sites (mean prevalence 13.8%, 93/674). PUUV infections were detected at four of 22 sites (mean prevalence 1.5%, 7/471), and respective PUUV sequences formed a novel phylogenetic clade, but DOBV infections were not detected at all. Leptospira infections were detected at 21 of 22 sites with the highest overall prevalence in field voles (Microtus agrestis) with 54.5% (6/11) and common voles (Microtus arvalis) with 30.3% (205/676). Leptospira-hantavirus coinfections were found in 6.6% (44/671) of common voles but only in two of 395 bank voles. TULV and Leptospira coinfection probability in common voles was driven by individual (age) and population-level factors. Coinfections seemed to be particularly associated with sites where Leptospira spp. prevalence exceeded 35%. Future investigations should evaluate public health consequences of this strong spatial clustering of coinfections.

Pathogenomic analyses of Mycobacterium microti, an ESX-1-deleted member of the Mycobacterium tuberculosis complex causing disease in various hosts.

Mycobacterium microti is an animal-adapted member of the Mycobacterium tuberculosis complex (MTBC), which was originally isolated from voles, but has more recently also been isolated from other selected mammalian hosts, including occasionally from humans. Here, we have generated and analysed the complete genome sequences of five representative vole and clinical M. microti isolates using PacBio- and Illumina-based technologies, and have tested their virulence and vaccine potential in SCID (severe combined immune deficient) mouse and/or guinea pig infection models. We show that the clinical isolates studied here cluster separately in the phylogenetic tree from vole isolates and other clades from publicly available M. microti genome sequences. These data also confirm that the vole and clinical M. microti isolates were all lacking the specific RD1mic region, which in other tubercle bacilli encodes the ESX-1 type VII secretion system. Biochemical analysis further revealed marked phenotypic differences between isolates in type VII-mediated secretion of selected PE and PPE proteins, which in part were attributed to specific genetic polymorphisms. Infection experiments in the highly susceptible SCID mouse model showed that the clinical isolates were significantly more virulent than the tested vole isolates, but still much less virulent than the M. tuberculosis H37Rv control strain. The strong attenuation of the ATCC 35872 vole isolate in immunocompromised mice, even compared to the attenuated BCG (bacillus Calmette-Guérin) vaccine, and its historic use in human vaccine trials encouraged us to test this strain's vaccine potential in a guinea pig model, where it demonstrated similar protective efficacy as a BCG control, making it a strong candidate for vaccination of immunocompromised individuals in whom BCG vaccination is contra-indicated. Overall, we provide new insights into the genomic and phenotypic variabilities and particularities of members of an understudied clade of the MTBC, which all share a recent common ancestor that is characterized by the deletion of the RD1mic region.

Rickettsia spp. in rodent-attached ticks in Estonia and first evidence of spotted fever group Rickettsia species Candidatus Rickettsia uralica in Europe.

BACKGROUND: Rickettsia spp. are human pathogens that cause a number of diseases and are transmitted by arthropods, such as ixodid ticks. Estonia is one of few regions where the distribution area of two medically important tick species, Ixodes persulcatus and I. ricinus, overlaps. The nidicolous rodent-associated Ixodes trianguliceps has also recently been shown to be present in Estonia. Although no data are available on human disease(s) caused by tick-borne Rickettsia spp. in Estonia, the presence of three Rickettsia species in non-nidicolous ticks has been previously reported. The aim of this study was to detect, identify and partially characterize Rickettsia species in nidicolous and non-nidicolous ticks attached to rodents in Estonia. RESULTS: Larvae and nymphs of I. ricinus (n = 1004), I. persulcatus (n = 75) and I. trianguliceps (n = 117), all removed from rodents and shrews caught in different parts of Estonia, were studied for the presence of Rickettsia spp. by nested PCR. Ticks were collected from 314 small animals of five species [Myodes glareolus (bank voles), Apodemus flavicollis (yellow necked mice), A. agrarius (striped field mice), Microtus subterranius (pine voles) and Sorex araneus (common shrews)]. Rickettsial DNA was detected in 8.7% (103/1186) of the studied ticks. In addition to identifying R. helvetica, which had been previously found in questing ticks, we report here the first time that the recently described I. trianguliceps-associated Candidatus Rickettsia uralica has been identified west of the Ural Mountains.

Epidemiological Characteristics of Rodents and Chiggers with Orientia Tsutsugamushi in the Republic of Korea.

A survey of rodents and chiggers associated with Orientia tsutsugamushi was conducted in a rural region of the Republic of Korea (Korea) between 2014 and 2018. Overall Apodemus agrarius 15.2% had the highest seropisitive for O. tsutsugamushi, followed by Myodes regulus 11.4%. Monthly risk factors using logistic regression analysis were not associated with O. tsutsugamushi infections in rodents. The overall prevalence rate of O. tsutsugamushi among chiggers was 0.3%. The chigger (Leptotrombidium scutellare) and monthly (October) risk factors were associated with O. tsutsugamushi human infections (P<0.05). Orientia tsutsugamushi infections are endemic in rodents in Korea and people, for example, soldiers who are active outdoors, must employ preventive measures, especially during October (P<0.05). When there are many reports of O. tsutsugamushi infections in Korea. The Boryong strain 85.7% (2/14) was the most common strain detected in chiggers, followed by the Shimokoshi 7.1% (1/14) and Karp 7.1% strains.

Two hundred and fifty-four metagenome-assembled bacterial genomes from the bank vole gut microbiota.

Vertebrate gut microbiota provide many essential services to their host. To better understand the diversity of such services provided by gut microbiota in wild rodents, we assembled metagenome shotgun sequence data from a small mammal, the bank vole Myodes glareolus (Rodentia, Cricetidae). We were able to identify 254 metagenome assembled genomes (MAGs) that were at least 50% (n = 133 MAGs), 80% (n = 77 MAGs) or 95% (n = 44 MAGs) complete. As typical for a rodent gut microbiota, these MAGs are dominated by taxa assigned to the phyla Bacteroidetes (n = 132 MAGs) and Firmicutes (n = 80), with some Spirochaetes (n = 15) and Proteobacteria (n = 11). Based on coverage over contigs, Bacteroidetes were estimated to be most abundant group, followed by Firmicutes, Spirochaetes and Proteobacteria. These draft bacterial genomes can be used freely to determine the likely functions of gut microbiota community composition in wild rodents.

High housing density increases stress hormone- or disease-associated fecal microbiota in male Brandt's voles (Lasiopodomys brandtii).

Density-dependence is an important mechanism in the population regulation of small mammals. Stressors induced by high-density (e.g., crowding and aggression) can cause physiological and neurological disorders, and are hypothesized to be associated with alterations in gut microbiota, which may in turn reduce the fitness of animals by increasing stress- or disease-associated microbes. In this study, we examined the effects of housing density on the hormone levels, immunity, and composition of gut microbiota in male Brandt's voles (Lasiopodomys brandtii) by conducting two specific housing density experiments with or without physical contact between voles. Voles in high density groups exhibited higher serum corticosterone (CORT), serotonin (5-HT), and immunoglobulin G (IgG) levels, as well as higher testosterone (T) levels only in the experiment with physical contact. Meanwhile, high-density treatments induced significant changes in the composition of gut microbiota by increasing disease-associated microbes. The levels of hormones and immunity (i.e., CORT, 5-HT, and IgG) elevated by the high density treatment were significantly correlated with some specific microbes. These results imply that high-density-induced stress may shape the fitness of animals under natural conditions by altering their gut microbiota. Our study provides novel insights into the potential roles of gut microbiota in the density-dependent population regulation of small rodents as well as the potential mechanisms underlying psychological disorders in humans and animals under crowded conditions.

Spatio-temporal trends in richness and persistence of bacterial communities in decline-phase water vole populations.

Understanding the driving forces that control vole population dynamics requires identifying bacterial parasites hosted by the voles and describing their dynamics at the community level. To this end, we used high-throughput DNA sequencing to identify bacterial parasites in cyclic populations of montane water voles that exhibited a population outbreak and decline in 2014-2018. An unexpectedly large number of 155 Operational Taxonomic Units (OTUs) representing at least 13 genera in 11 families was detected. Individual bacterial richness was higher during declines, and vole body condition was lower. Richness as estimated by Chao2 at the local population scale did not exhibit clear seasonal or cycle phase-related patterns, but at the vole meta-population scale, exhibited seasonal and phase-related patterns. Moreover, bacterial OTUs that were detected in the low density phase were geographically widespread and detected earlier in the outbreak; some were associated with each other. Our results demonstrate the complexity of bacterial community patterns with regard to host density variations, and indicate that investigations about how parasites interact with host populations must be conducted at several temporal and spatial scales: multiple times per year over multiple years, and at both local and long-distance dispersal scales for the host(s) under consideration.

Selective Predation by Owls on Infected Bank Voles (Myodes glareolus) as a Possible Sentinel of Tularemia Outbreaks.

Tularemia is a widely spread zoonotic disease in the northern hemisphere, caused by the bacterium Francisella tularensis. In humans, tularemia is an acute febrile illness with incidence peaks in late summer to early autumn of outbreak years, but there is no early warning system in place that can reduce the impact of disease by providing timely risk information. In this study, we revisit previously unpublished data on F. tularensis in water, sediment, soil, and small mammals from 1984 in northern Sweden. In addition, we used human case data from the national surveillance system for tularemia in the same year. In the environmental and small mammal material, bank vole (Myodes glareolus) samples from urine and bladder were the only samples that tested positive for F. tularensis. The prevalence of F. tularensis among trapped bank voles was 13.5%, although all six bank voles that were retrieved from owl nest boxes in early May tested positive. Forty-two human tularemia cases were reported from August to December in 1984. Based on these results, we encourage investigating the potential role of tularemia-infected bank voles retrieved from owl nest boxes in spring as an early warning for outbreaks of tularemia among humans in summer and autumn of the same year.

Gut microbial diversity across a contact zone for California voles: Implications for lineage divergence of hosts and mitonuclear mismatch in the assembly of the mammalian gut microbiome.

Gut microbial diversity is thought to reflect the co-evolution of microbes and their hosts as well as current host-specific attributes such as genetic background and environmental setting. To explore interactions among these parameters, we characterized variation in gut microbiome composition of California voles (Microtus californicus) across a contact zone between two recently diverged lineages of this species. Because this contact zone contains individuals with mismatched mitochondrial-nuclear genomes (cybrids), it provides an important opportunity to explore how different components of the genotype contribute to gut microbial diversity. Analyses of bacterial 16S rRNA sequences and joint species distribution modelling revealed that host genotypes and genetic differentiation among host populations together explained more than 50% of microbial community variation across our sampling transect. The ranked importance (most to least) of factors contributing to gut microbial diversity in our study populations were: genome-wide population differentiation, local environmental conditions, and host genotypes. However, differences in microbial communities among vole populations (ß-diversity) did not follow patterns of lineage divergence (i.e., phylosymbiosis). Instead, among-population variation was best explained by the spatial distribution of hosts, as expected if the environment is a primary source of gut microbial diversity (i.e., dispersal limitation hypothesis). Across the contact zone, several bacterial taxa differed in relative abundance between the two parental lineages as well as among individuals with mismatched mitochondrial and nuclear genomes. Thus, genetic divergence among host lineages and mitonuclear genomic mismatches may also contribute to microbial diversity by altering interactions between host genomes and gut microbiota (i.e., hologenome speciation hypothesis).

Muskrats are greater carriers of pathogenic Leptospira than coypus in ecosystems with temperate climates.

Knowledge on the possible sources of human leptospirosis, other than rats, is currently lacking. To assess the distribution pattern of exposure and infection by Leptospira serogroups in the two main semi-aquatic rodents of Western France, coypus (Myocastor coypus) and muskrats (Ondatra zibethicus), results of micro-agglutination testing and renal tissue PCR were used. In coypus, the apparent prevalence was 11% (n = 524, CI95% = [9% - 14%]), seroprevalence was 42% (n = 590, CI95% = [38% - 46%]), and the predominant serogroup was Australis (84%). In muskrats, the apparent prevalence was 33% (n = 274, CI95% = [27% - 39%]), seroprevalence was 57% (n = 305, CI95% = [52% - 63%]), and the predominant serogroup was Grippotyphosa (47%). Muskrats should therefore be considered an important source of Grippotyphosa infection in humans and domestic animals exposed in this part of France.

Genome assembly and transcriptome analysis provide insights into the antischistosome mechanism of Microtus fortis.

Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection. However, the underlying molecular mechanisms of this resistance are not yet known. Here, we perform the first de novo genome assembly of M. fortis, comprehensive gene annotation analysis, and evolution analysis. Furthermore, we compare the recovery rate of schistosomes, pathological changes, and liver transcriptomes between M. fortis and mice at different time points after infection. We observe that the time and type of immune response in M. fortis are different from those in mice. M. fortis activates immune and inflammatory responses on the 10th day post infection, such as leukocyte extravasation, antibody activation, Fc-gamma receptor-mediated phagocytosis, and the interferon signaling cascade, which play important roles in preventing the development of schistosomes. In contrast, an intense immune response occurrs in mice at the late stages of infection and could not eliminate schistosomes. Infected mice suffer severe pathological injury and continuous decreases in cell cycle, lipid metabolism, and other functions. Our findings offer new insights into the intrinsic resistance mechanism of M. fortis against schistosome infection. The genome sequence also provides the basis for future studies of other important traits in M. fortis.

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.