BACKGROUND: The human gut microbiota is a complex community comprised of trillions of bacteria and is critical for the digestion and absorption of nutrients. Bacterial communities of the intestinal microbiota influence the development of several conditions and diseases. We studied the effect of host genetics on gut microbial composition using Collaborative Cross (CC) mice. CC mice are a panel of mice that are genetically diverse across strains, but genetically identical within a given strain allowing repetition and deeper analysis than is possible with other collections of genetically diverse mice. RESULTS: 16S rRNA from the feces of 167 mice from 28 different CC strains was sequenced and analyzed using the Qiime2 pipeline. We observed a large variance in the bacterial composition across CC strains starting at the phylum level. Using bacterial composition data, we identified 17 significant Quantitative Trait Loci (QTL) linked to 14 genera on 9 different mouse chromosomes. Genes within these intervals were analyzed for significant association with pathways and the previously known human GWAS database using Enrichr analysis and Genecards database. Multiple host genes involved in obesity, glucose homeostasis, immunity, neurological diseases, and many other protein-coding genes located in these regions may play roles in determining the composition of the gut microbiota. A subset of these CC mice was infected with Salmonella Typhimurium. Using infection outcome data, an increase in abundance of genus Lachnospiraceae and decrease in genus Parasutterella correlated with positive health outcomes after infection. Machine learning classifiers accurately predicted the CC strain and the infection outcome using pre-infection bacterial composition data from the feces. CONCLUSION: Our study supports the hypothesis that multiple host genes influence the gut microbiome composition and homeostasis, and that certain organisms may influence health outcomes after S. Typhimurium infection. Video Abstract.

BACKGROUND: Following solid organ transplantation, tacrolimus (TAC) is an essential drug in the immunosuppressive strategy. Its use constitutes a challenge due to its narrow therapeutic index and its high inter- and intra-pharmacokinetic (PK) variability. As the contribution of the gut microbiota to drug metabolism is now emerging, it might be explored as one of the factors explaining TAC PK variability. Herein, we explored the consequences of TAC administration on the gut microbiota composition. Reciprocally, we studied the contribution of the gut microbiota to TAC PK, using a combination of in vivo and in vitro models. RESULTS: TAC oral administration in mice resulted in compositional alterations of the gut microbiota, namely lower evenness and disturbance in the relative abundance of specific bacterial taxa. Compared to controls, mice with a lower intestinal microbial load due to antibiotics administration exhibit a 33% reduction in TAC whole blood exposure and a lower inter-individual variability. This reduction in TAC levels was strongly correlated with higher expression of the efflux transporter ABCB1 (also known as the p-glycoprotein (P-gp) or the multidrug resistance protein 1 (MDR1)) in the small intestine. Conventionalization of germ-free mice confirmed the ability of the gut microbiota to downregulate ABCB1 expression in a site-specific fashion. The functional inhibition of ABCB1 in vivo by zosuquidar formally established the implication of this efflux transporter in the modulation of TAC PK by the gut microbiota. Furthermore, we showed that polar bacterial metabolites could recapitulate the transcriptional regulation of ABCB1 by the gut microbiota, without affecting its functionality. Finally, whole transcriptome analyses pinpointed, among others, the Constitutive Androstane Receptor (CAR) as a transcription factor likely to mediate the impact of the gut microbiota on ABCB1 transcriptional regulation. CONCLUSIONS: We highlight for the first time how the modulation of ABCB1 expression by bacterial metabolites results in changes in TAC PK, affecting not only blood levels but also the inter-individual variability. More broadly, considering the high number of drugs with unexplained PK variability transported by ABCB1, our work is of clinical importance and paves the way for incorporating the gut microbiota in prediction algorithms for dosage of such drugs. Video Abstract.

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.

BACKGROUND: Understanding how the host's microbiome shapes phenotypes and participates in the host response to selection is fundamental for evolutionists and animal and plant breeders. Currently, selection for resilience is considered a critical step in improving the sustainability of livestock systems. Environmental variance (V E), the within-individual variance of a trait, has been successfully used as a proxy for animal resilience. Selection for reduced V E could effectively shift gut microbiome composition; reshape the inflammatory response, triglyceride, and cholesterol levels; and drive animal resilience. This study aimed to determine the gut microbiome composition underlying the V E of litter size (LS), for which we performed a metagenomic analysis in two rabbit populations divergently selected for low (n = 36) and high (n = 34) V E of LS. Partial least square-discriminant analysis and alpha- and beta-diversity were computed to determine the differences in gut microbiome composition among the rabbit populations. RESULTS: We identified 116 KEGG IDs, 164 COG IDs, and 32 species with differences in abundance between the two rabbit populations studied. These variables achieved a classification performance of the V E rabbit populations of over than 80%. Compared to the high V E population, the low V E (resilient) population was characterized by an underrepresentation of Megasphaera sp., Acetatifactor muris, Bacteroidetes rodentium, Ruminococcus bromii, Bacteroidetes togonis, and Eggerthella sp. and greater abundances of Alistipes shahii, Alistipes putredinis, Odoribacter splanchnicus, Limosilactobacillus fermentum, and Sutterella, among others. Differences in abundance were also found in pathways related to biofilm formation, quorum sensing, glutamate, and amino acid aromatic metabolism. All these results suggest differences in gut immunity modulation, closely related to resilience. CONCLUSIONS: This is the first study to show that selection for V E of LS can shift the gut microbiome composition. The results revealed differences in microbiome composition related to gut immunity modulation, which could contribute to the differences in resilience among rabbit populations. The selection-driven shifts in gut microbiome composition should make a substantial contribution to the remarkable genetic response observed in the V E rabbit populations. Video Abstract.

BACKGROUND: Despite the knowledge that the soil-plant-microbiome nexus is shaped by interactions amongst its members, very little is known about how individual symbioses regulate this shaping. Even less is known about how the agriculturally important symbiosis of nitrogen-fixing rhizobia with legumes is impacted according to soil type, yet this knowledge is crucial if we are to harness or improve it. We asked how the plant, soil and microbiome are modulated by symbiosis between the model legume Medicago truncatula and different strains of Sinorhizobium meliloti or Sinorhizobium medicae whose nitrogen-fixing efficiency varies, in three distinct soil types that differ in nutrient fertility, to examine the role of the soil environment upon the plant-microbe interaction during nodulation. RESULTS: The outcome of symbiosis results in installment of a potentially beneficial microbiome that leads to increased nutrient uptake that is not simply proportional to soil nutrient abundance. A number of soil edaphic factors including Zn and Mo, and not just the classical N/P/K nutrients, group with microbial community changes, and alterations in the microbiome can be seen across different soil fertility types. Root endosphere emerged as the plant microhabitat more affected by this rhizobial efficiency-driven community reshaping, manifested by the accumulation of members of the phylum Actinobacteria. The plant in turn plays an active role in regulating its root community, including sanctioning low nitrogen efficiency rhizobial strains, leading to nodule senescence in particular plant-soil-rhizobia strain combinations. CONCLUSIONS: The microbiome-soil-rhizobial dynamic strongly influences plant nutrient uptake and growth, with the endosphere and rhizosphere shaped differentially according to plant-rhizobial interactions with strains that vary in nitrogen-fixing efficiency levels. These results open up the possibility to select inoculation partners best suited for plant, soil type and microbial community. Video Abstract.

BACKGROUND: The resistome, the collection of antibiotic resistance genes (ARGs) in a microbiome, is increasingly recognised as relevant to the development of clinically relevant antibiotic resistance. Many metagenomic studies have reported resistome differences between groups, often in connection with disease and/or antibiotic treatment. However, the consistency of resistome associations with antibiotic- and non-antibiotic-treated diseases has not been established. In this study, we re-analysed human gut microbiome data from 26 case-control studies to assess the link between disease and the resistome. RESULTS: The human gut resistome is highly variable between individuals both within and between studies, but may also vary significantly between case and control groups even in the absence of large taxonomic differences. We found that for diseases commonly treated with antibiotics, namely cystic fibrosis and diarrhoea, patient microbiomes had significantly elevated ARG abundances compared to controls. Disease-associated resistome expansion was found even when ARG abundance was high in controls, suggesting ongoing and additive ARG acquisition in disease-associated strains. We also found a trend for increased ARG abundance in cases from some studies on diseases that are not treated with antibiotics, such as colorectal cancer. CONCLUSIONS: Diseases commonly treated with antibiotics are associated with expanded gut resistomes, suggesting that historical exposure to antibiotics has exerted considerable selective pressure for ARG acquisition in disease-associated strains. Video Abstract.

BACKGROUND: During development, elevated levels of maternal glucocorticoids (GCs) can have detrimental effects on offspring morphology, cognition, and behavior as well as physiology and metabolism. Depending on the timing of exposure, such effects may vary in strength or even reverse in direction, may alleviate with age, or may concern more stable and long-term programming of phenotypic traits. Maternal effects on gut bacterial diversity, composition, and function, and the persistence of such effects into adulthood of long-lived model species in the natural habitats remain underexplored. RESULTS: In a cross-sectional sample of infant, juvenile, and adult Assamese macaques, the timing of exposure to elevated maternal GCs during ontogeny was associated with the gut bacterial community of the offspring. Specifically, naturally varying maternal GC levels during early but not late gestation or lactation were associated with reduced bacterial richness. The overall effect of maternal GCs during early gestation on the gut bacterial composition and function exacerbated with offspring age and was 10 times stronger than the effect associated with exposure during late prenatal or postnatal periods. Instead, variation in maternal GCs during the late prenatal or postnatal period had less pronounced or less stable statistical effects and therefore a weaker effect on the entire bacterial community composition, particularly in adult individuals. Finally, higher early prenatal GCs were associated with an increase in the relative abundance of several potential pro-inflammatory bacteria and a decrease in the abundance of Bifidobacterium and other anti-inflammatory taxa, an effect that exacerbated with age. CONCLUSIONS: In primates, the gut microbiota can be shaped by developmental effects with strong timing effects on plasticity and potentially detrimental consequences for adult health. Together with results on other macaque species, this study suggests potential detrimental developmental effects similar to rapid inflammaging, suggesting that prenatal exposure to high maternal GC concentrations is a common cause underlying both phenomena. Our findings await confirmation by metagenomic functional and causal analyses and by longitudinal studies of long-lived, ecologically flexible primates in their natural habitat, including developmental effects that originate before birth. Video Abstract.

BACKGROUND: Antibiotics are widely used for prophylactic therapy and for improving the growth performance of chicken. The problem of bacterial drug resistance caused by antibiotic abuse has previously attracted extensive attention; however, the influence of early-day use of prophylactic antibiotics on the gut microflora and on the disease resistance ability in chicks has not been explored. Here, we comprehensively evaluate the growth performance, gut microbial dynamics, level of antibiotic resistance genes (ARGs) in the gut microbial community, and resistance to H9N2 avian influenza virus (AIV) in chickens following long-term and short-term early-day prophylactic antibiotic treatment. RESULTS: Unexpectedly, long-term prophylactic enrofloxacin treatment slowed the growth rate of chickens, whereas short-term antibiotics treatments were found to increase the growth rate, but these changes were not statistically significant. Strikingly, expansions of Escherichia-Shigella populations were observed in early-life prophylactic antibiotics-treated groups of chickens, which is in contrast to the general perception that antibiotics should control their pathogenicity in chicks. The gut microbiota composition of chickens treated long term with antibiotics or received early-day antibiotics treatment tend to be more dramatically disturbed compared to the gut microbiome of chickens treated with antibiotics for a short term at a later date, especially after H9N2 AIV infection. CONCLUSIONS: Our data provide evidence that early-day and long-term antibiotic treatments have a more adverse effect on the intestinal microbiome of chickens, compared to short-term late age antibiotic treatment. Furthermore, our metagenomic data reveal that both long-term and short-term antibiotic treatment increase the relative abundance of ARGs. Our findings highlight the adverse effects of prophylactic antibiotic treatment and provide a theoretical basis for the cautious administration of antibiotics in food-producing animal management. Video Abstract.

BACKGROUND: Ferromanganese nodule-bearing deep-sea sediments cover vast areas of the ocean floor, representing a distinctive habitat in the abyss. These sediments harbor unique conditions characterized by high iron concentration and low degradable nutrient levels, which pose challenges to the survival and growth of most microorganisms. While the microbial diversity in ferromanganese nodule-associated sediments has been surveyed several times, little is known about the functional capacities of the communities adapted to these unique habitats. RESULTS: Seven sediment samples collected adjacent to ferromanganese nodules from the Clarion-Clipperton Fracture Zone (CCFZ) in the eastern Pacific Ocean were subjected to metagenomic analysis. As a result, 179 high-quality metagenome-assembled genomes (MAGs) were reconstructed and assigned to 21 bacterial phyla and 1 archaeal phylum, with 88.8% of the MAGs remaining unclassified at the species level. The main mechanisms of resistance to heavy metals for microorganisms in sediments included oxidation (Mn), reduction (Cr and Hg), efflux (Pb), synergy of reduction and efflux (As), and synergy of oxidation and efflux (Cu). Iron, which had the highest content among all metallic elements, may occur mainly as Fe(III) that potentially functioned as an electron acceptor. We found that microorganisms with a diverse array of CAZymes did not exhibit higher community abundance. Instead, microorganisms mainly obtained energy from oxidation of metal (e.g., Mn(II)) and sulfur compounds using oxygen or nitrate as an electron acceptor. Chemolithoautotrophic organisms (Thaumarchaeota and Nitrospirota phyla) were found to be potential manganese oxidizers. The functional profile analysis of the dominant microorganisms further indicated that utilization of inorganic nutrients by redox reactions (rather than organic nutrient metabolism) is a major adaptive strategy used by microorganisms to support their survival in the ferromanganese nodule sediments. CONCLUSIONS: This study provides a comprehensive metagenomic analysis of microbes inhabiting metal-rich ferromanganese nodule sediments. Our results reveal extensive redundancy across taxa for pathways of metal resistance and transformation, the highly diverse mechanisms used by microbes to obtain nutrition, and their participation in various element cycles in these unique environments. Video Abstract.

BACKGROUND: Porphyromonas gingivalis (hereafter "Pg") is an oral pathogen that has been hypothesized to act as a keystone driver of inflammation and periodontal disease. Although Pg is most readily recovered from individuals with actively progressing periodontal disease, healthy individuals and those with stable non-progressing disease are also colonized by Pg. Insights into the factors shaping the striking strain-level variation in Pg, and its variable associations with disease, are needed to achieve a more mechanistic understanding of periodontal disease and its progression. One of the key forces often shaping strain-level diversity in microbial communities is infection of bacteria by their viral (phage) predators and symbionts. Surprisingly, although Pg has been the subject of study for over 40 years, essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg. RESULTS: Here we systematically addressed the question of whether Pg are infected by phages-and we found that they are. We found that prophages are common in Pg, they are genomically diverse, and they encode genes that have the potential to alter Pg physiology and interactions. We found that phages represent unrecognized targets of the prevalent CRISPR-Cas defense systems in Pg, and that Pg strains encode numerous additional mechanistically diverse candidate anti-phage defense systems. We also found that phages and candidate anti-phage defense system elements together are major contributors to strain-level diversity and the species pangenome of this oral pathogen. Finally, we demonstrate that prophages harbored by a model Pg strain are active in culture, producing extracellular viral particles in broth cultures. CONCLUSION: This work definitively establishes that phages are a major unrecognized force shaping the ecology and intra-species strain-level diversity of the well-studied oral pathogen Pg. The foundational phage sequence datasets and model systems that we establish here add to the rich context of all that is already known about Pg, and point to numerous avenues of future inquiry that promise to shed new light on fundamental features of phage impacts on human health and disease broadly. Video Abstract.

BACKGROUND: Cervicovaginal inflammation has been linked to negative reproductive health outcomes including the acquisition of HIV, other sexually transmitted infections, and cervical carcinogenesis. While changes to the vaginal microbiome have been linked to genital inflammation, the molecular relationships between the functional components of the microbiome with cervical immunology in the reproductive tract are understudied, limiting our understanding of mucosal biology that may be important for reproductive health. RESULTS: In this study, we used a multi'-omics approach to profile cervicovaginal samples collected from 43 Canadian women to characterize host, immune, functional microbiome, and metabolome features of cervicovaginal inflammation. We demonstrate that inflammation is associated with lower amounts of L. crispatus and higher levels of cervical antigen-presenting cells (APCs). Proteomic analysis showed an upregulation of pathways related to neutrophil degranulation, complement, and leukocyte migration, with lower levels of cornified envelope and cell-cell adherens junctions. Functional microbiome analysis showed reductions in carbohydrate metabolism and lactic acid, with increases in xanthine and other metabolites. Bayesian network analysis linked L. crispatus with glycolytic and nucleotide metabolism, succinate and xanthine, and epithelial proteins SCEL and IVL as major molecular features associated with pro-inflammatory cytokines and increased APCs. CONCLUSIONS: This study identified key molecular and immunological relationships with cervicovaginal inflammation, including higher APCs, bacterial metabolism, and proteome alterations that underlie inflammation. As APCs are involved in HIV transmission, parturition, and cervical cancer progression, further studies are needed to explore the interactions between these cells, bacterial metabolism, mucosal immunity, and their relationship to reproductive health. Video Abstract.

BACKGROUND: Bovine respiratory disease (BRD) is one of the most common diseases in intensively managed cattle, often resulting in high morbidity and mortality. Although several pathogens have been isolated and extensively studied, the complete infectome of the respiratory complex consists of a more extensive range unrecognised species. Here, we used total RNA sequencing (i.e., metatranscriptomics) of nasal and nasopharyngeal swabs collected from animals with and without BRD from two cattle feedlots in Australia. RESULTS: A high abundance of bovine nidovirus, influenza D, bovine rhinitis A and bovine coronavirus was found in the samples. Additionally, we obtained the complete or near-complete genome of bovine rhinitis B, enterovirus E1, bovine viral diarrhea virus (sub-genotypes 1a and 1c) and bovine respiratory syncytial virus, and partial sequences of other viruses. A new species of paramyxovirus was also identified. Overall, the most abundant RNA virus, was the bovine nidovirus. Characterisation of bacterial species from the transcriptome revealed a high abundance and diversity of Mollicutes in BRD cases and unaffected control animals. Of the non-Mollicutes species, Histophilus somni was detected, whereas there was a low abundance of Mannheimia haemolytica. CONCLUSION: This study highlights the use of untargeted sequencing approaches to study the unrecognised range of microorganisms present in healthy or diseased animals and the need to study previously uncultured viral species that may have an important role in cattle respiratory disease. Video Abstract.

BACKGROUND: Ticks can transmit a broad variety of pathogens of medical importance, including Borrelia afzelii, the causative agent of Lyme borreliosis in Europe. Tick microbiota is an important factor modulating, not only vector physiology, but also the vector competence. Anti-microbiota vaccines targeting keystone taxa of tick microbiota can alter tick feeding and modulate the taxonomic and functional profiles of bacterial communities in the vector. However, the impact of anti-microbiota vaccine on tick-borne pathogen development within the vector has not been tested. RESULTS: Here, we characterized the Ixodes ricinus microbiota modulation in response to B. afzelii infection and found that the pathogen induces changes in the microbiota composition, its beta diversity and structure of bacterial community assembly. Tick microbiota perturbation by anti-microbiota antibodies or addition of novel commensal bacteria into tick midguts causes departures from the B. afzelii-induced modulation of tick microbiota which resulted in a lower load of the pathogen in I. ricinus. Co-occurrence networks allowed the identification of emergent properties of the bacterial communities which better defined the Borrelia infection-refractory states of the tick microbiota. CONCLUSIONS: These findings suggest that Borrelia is highly sensitive to tick microbiota perturbations and that departure from the modulation induced by the pathogen in the vector microbiota pose a high cost to the spirochete. Network analysis emerges as a suitable tool to identify emergent properties of the vector microbiota associated with infection-refractory states. Anti-microbiota vaccines can be used as a tool for microbiota perturbation and control of important vector-borne pathogens. Video Abstract.

BACKGROUND: Secondary bacterial infections and pneumonia are major mortality causes of respiratory viruses, and the disruption of the upper respiratory tract (URT) microbiota is a crucial component of this process. However, whether this URT dysbiosis associates with the viral species (in other words, is viral type-specific) is unclear. RESULTS: Here, we recruited 735 outpatients with upper respiratory symptoms, identified the infectious virus types in 349 participants using multiplex RT-PCR, and profiled their upper respiratory microbiome using the 16S ribosomal RNA gene and metagenomic gene sequencing. Microbial and viral data were subsequently used as inputs for multivariate analysis aimed at revealing viral type-specific disruption of the upper respiratory microbiota. We found that the oropharyngeal microbiota shaped by influenza A virus (FluA), influenza B virus (FluB), respiratory syncytial virus (RSV), and human rhinovirus (HRV) infections exhibited three distinct patterns of dysbiosis, and Veillonella was identified as a prominent biomarker for any type of respiratory viral infections. Influenza virus infections are significantly correlated with increased oropharynx microbiota diversity and enrichment of functional metabolic pathways such as L-arginine biosynthesis and tetracycline resistance gene tetW. We used the GRiD algorithm and found the predicted growth rate of common respiratory pathogens was increased upon influenza virus infection, while commensal bacteria, such as Streptococcus infantis and Streptococcus mitis, may act as a colonization resistance to the overgrowth of these pathogens. CONCLUSIONS: We found that respiratory viral infections are linked with viral type-specific disruption of the upper respiratory microbiota, particularly, influenza infections uniquely associated with increased microbial diversity and growth rates of specific pathogens in URT. These findings are essential for clarifying the differences and dynamics of respiratory microbiota in healthy participants and acute respiratory viral infections, which contribute to elucidating the pathogenesis of viral-host-bacterial interactions to provide insights into future studies on effective prevention and treatment of respiratory tract infections. Video Abstract.

BACKGROUND: Jellyfish blooms represent a significant but largely overlooked source of labile organic matter (jelly-OM) in the ocean, characterized by a high protein content. Decaying jellyfish are important carriers for carbon export to the ocean's interior. To accurately incorporate them into biogeochemical models, the interactions between microbes and jelly-OM have yet to be fully characterized. We conducted jelly-OM enrichment experiments in microcosms to simulate the scenario experienced by the coastal pelagic microbiome after the decay of a jellyfish bloom. We combined metagenomics, endo- and exo-metaproteomic approaches to obtain a mechanistic understanding on the metabolic network operated by the jelly-OM degrading bacterial consortium. RESULTS: Our analysis revealed that OM released during the decay of jellyfish blooms triggers a rapid shuffling of the taxonomic and functional profile of the pelagic bacterial community, resulting in a significant enrichment of protein/amino acid catabolism-related enzymes in the jelly-OM degrading community dominated by Pseudoalteromonadaceae, Alteromonadaceae and Vibrionaceae, compared to unamended control treatments. In accordance with the proteinaceous character of jelly-OM, Pseudoalteromonadaceae synthesized and excreted enzymes associated with proteolysis, while Alteromonadaceae contributed to extracellular hydrolysis of complex carbohydrates and organophosphorus compounds. In contrast, Vibrionaceae synthesized transporter proteins for peptides, amino acids and carbohydrates, exhibiting a cheater-type lifestyle, i.e. benefiting from public goods released by others. In the late stage of jelly-OM degradation, Rhodobacteraceae and Alteromonadaceae became dominant, growing on jelly-OM left-overs or bacterial debris, potentially contributing to the accumulation of dissolved organic nitrogen compounds and inorganic nutrients, following the decay of jellyfish blooms. CONCLUSIONS: Our findings indicate that specific chemical and metabolic fingerprints associated with decaying jellyfish blooms are substantially different to those previously associated with decaying phytoplankton blooms, potentially altering the functioning and biogeochemistry of marine systems. We show that decaying jellyfish blooms are associated with the enrichment in extracellular collagenolytic bacterial proteases, which could act as virulence factors in human and marine organisms' disease, with possible implications for marine ecosystem services. Our study also provides novel insights into niche partitioning and metabolic interactions among key jelly-OM degraders operating a complex metabolic network in a temporal cascade of biochemical reactions to degrade pulses of jellyfish-bloom-specific compounds in the water column. Video Abstract.

BACKGROUND: For more than a century, the Koch's postulates have been the golden rule for determining the causative agents in diseases. However, in cases of multiple pathogens-one disease, in which different pathogens can cause the same disease, the selection of microorganisms that regress infection is hard when Koch's postulates are applied. Microbiome approaches can obtain relatively complete information about disease-related microorganisms and can guide the selection of target microorganisms for regression infection. In the present study, whitish muscle syndrome (WMS) of Scylla paramamosain, which has typical symptoms with whitish muscle and blackened hemolymph was used as an example to establish a new research strategy that integrates microbiome approaches and Koch's postulates to determinate causative agents of multiple pathogens-one disease. RESULTS: Microbiome results revealed that Aeromonas, Acinetobacter, Shewanella, Chryseomicrobium, Exiguobacterium, Vibrio and Flavobacterium, and Kurtzmaniella in hemolymph were bacterial and fungal indicators for WMS. A total of 23 bacteria and 14 fungi were isolated from hemolymph and muscle tissues, and among the bacteria, Shewanella chilikensis, S. xiamenensis, Vibrio alginolyticus, S. putrefaciens, V. fluvialis, and V. parahaemolyticus were present in hemolymph and/or muscle tissues in each WMS crab, and the last three species were also present in three Healthy crabs. The target bacteria and fungi were further screened to regression infections based on two criteria: whether they belonged to the indicator genera for WMS, whether they were isolated from both hemolymph and muscle tissues in most WMS crabs. Only S. chilikensis, S. putrefaciens, S. xiamenensis, V. alginolyticus, V. fluvialis, and V. parahaemolyticus met both two criteria. The six bacteria that met both two criteria and six fungi and another bacterium that unmatched any of two criteria were used to perform regression infection experiments based on Koch's postulates. S. chilikensis, S. putrefaciens, S. xiamenensis, V. alginolyticus, V. fluvialis, and V. parahaemolyticus met both two criteria, and the results indicate that they cause WMS in crabs independently. CONCLUSIONS: This study fully demonstrated that our research strategy that integrates the microbiome and Koch's postulates can maximize the ability to catch pathogens in one net for the situation of multiple pathogens-one disease. Video Abstract.

BACKGROUND: Microbes constitute almost the entire biological community in subsurface groundwater and play an important role in ecological evolution and global biogeochemical cycles. Ecological baseline as a fundamental reference with less human interference has been investigated in surface ecosystems such as soils, rivers, and ocean, but the existence of groundwater microbial ecological baseline (GMEB) is still an open question so far. RESULTS: Based on high-throughput sequencing information derived from national monitoring of 733 newly constructed wells, we find that bacterial communities in pristine groundwater exhibit a significant lateral diversity gradient and gradually approach the topsoil microbial latitudinal diversity gradient with decreasing burial depth of phreatic water. Among 74 phyla dominated by Proteobacteria in groundwater, Patescibacteria act as keystone taxa that harmonize microbes in shallower aquifers and accelerate decline in bacterial diversity with increasing well-depth. Decreasing habitat niche breadth with increasing well-depth suggests a general change in the relationship among key microbes from closer cooperation in shallow to stronger competition in deep groundwater. Unlike surface-water microbes, microbial communities in pristine groundwater are predominantly shaped by deterministic processes, potentially associated with nutrient sequestration under dark and anoxic environments in aquifers. CONCLUSIONS: By unveiling the biogeographic patterns and mechanisms controlling the community assembly of microbes in pristine groundwater throughout China, we firstly confirm the existence of GMEB in shallower aquifers and propose Groundwater Microbial Community Index (GMCI) to evaluate anthropogenic impact, which highlights the importance of GMEB in groundwater water security and health diagnosis. Video Abstract.

BACKGROUND: Aberrant tryptophan (Trp)-kynurenine (Kyn) metabolism has been implicated in the pathogenesis of human disease. In particular, populations with long-term western-style diets are characterized by an excess of Kyn in the plasma. Host-gut microbiota interactions are dominated by diet and are essential for maintaining host metabolic homeostasis. However, the role of western diet-disturbed gut microbiota-colonocyte interactions in Trp metabolism remains to be elucidated. RESULTS: Here, 4-week-old mice were fed with a high-fat diet (HFD), representing a typical western diet, for 4 weeks, and multi-omics approaches were adopted to determine the mechanism by which HFD disrupted gut microbiota-colonocyte interplay causing serum Trp-Kyn metabolism dysfunction. Our results showed that colonocyte-microbiota interactions dominated the peripheral Kyn pathway in HFD mice. Mechanistically, persistent HFD-impaired mitochondrial bioenergetics increased colonic epithelial oxygenation and caused metabolic reprogramming in colonites to support the expansion of Proteobacteria in the colon lumen. Phylum Proteobacteria-derived lipopolysaccharide (LPS) stimulated colonic immune responses to upregulate the indoleamine 2,3-dioxygenase 1 (IDO1)-mediated Kyn pathway, leading to Trp depletion and Kyn accumulation in the circulation, which was further confirmed by transplantation of Escherichia coli (E.coli) indicator strains and colonic IDO1 depletion. Butyrate supplementation promoted mitochondrial functions in colonocytes to remodel the gut microbiota in HFD mice, consequently ameliorating serum Kyn accumulation. CONCLUSIONS: Our results highlighted that HFD disrupted the peripheral Kyn pathway in a gut microbiota-dependent manner and that the continuous homeostasis of gut bacteria-colonocytes interplay played a central role in the regulation of host peripheral Trp metabolism. Meanwhile, this study provided new insights into therapies against western diet-related metabolic disorders. Video Abstract.

BACKGROUND: Lactobacillus species in gut microbiota shows great promise in alleviation of metabolic diseases. However, little is known about the molecular mechanism of how Lactobacillus interacts with metabolites in circulation. Here, using high nucleoside intake to induce hyperuricemia in mice, we investigated the improvement in systemic urate metabolism by oral administration of L. plantarum via different host pathways. RESULTS: Gene expression analysis demonstrated that L. plantarum inhibited the activity of xanthine oxidase and purine nucleoside phosphorylase in liver to suppress urate synthesis. The gut microbiota composition did not dramatically change by oral administration of L. plantarum over 14 days, indicated by no significant difference in α and β diversities. However, multi-omic network analysis revealed that increase of L. plantarum and decrease of L. johnsonii contributed to a decrease in serum urate levels. Besides, genomic analysis and recombinant protein expression showed that three ribonucleoside hydrolases, RihA-C, in L. plantarum rapidly and cooperatively catalyzed the hydrolysis of nucleosides into nucleobases. Furthermore, the absorption of nucleobase by intestinal epithelial cells was less than that of nucleoside, which resulted in a reduction of urate generation, evidenced by the phenomenon that mice fed with nucleobase diet generated less serum urate than those fed with nucleoside diet over a period of 9-day gavage. CONCLUSION: Collectively, our work provides substantial evidence identifying the specific role of L. plantarum in improvement of urate circulation. We highlight the importance of the enzymes RihA-C existing in L. plantarum for the urate metabolism in hyperuricemia mice induced by a high-nucleoside diet. Although the direct connection between nucleobase transport and host urate levels has not been identified, the lack of nucleobase transporter in intestinal epithelial cells might be important to decrease its absorption and metabolization for urate production, leading to the decrease of serum urate in host. These findings provide important insights into urate metabolism regulation. Video Abstract.

BACKGROUND: Individuals that band together create new ecological opportunities for microorganisms. In vertical transmission, theory predicts a conserved microbiota within lineages, especially social bees. Bees exhibit solitary to social behavior among and/or within species, while life cycles can be annual or perennial. Bee nests may be used over generations or only once, and foraging ecology varies widely. To assess which traits are associated with bee microbiomes, we analyzed microbial diversity within solitary and social bees of Apidae, Colletidae, and Halictidae, three bee families in Panama's tropical forests. Our analysis considered the microbiome of adult gut contents replicated through time, localities, and seasons (wet and dry) and included bee morphology and comparison to abdominal (dissected) microbiota. Diversity and distribution of tropical bee microbes (TBM) within the corbiculate bee clade were emphasized. RESULTS: We found the eusocial corbiculate bees tended to possess a more conserved gut microbiome, attributable to vertical transmission, but microbial composition varied among closely related species. Euglossine bees (or orchid bees), corbiculates with mainly solitary behavior, had more variable gut microbiomes. Their shorter-tongued and highly seasonal species displayed greater diversity, attributable to flower-visiting habits. Surprisingly, many stingless bees, the oldest corbiculate clade, lacked bacterial genera thought to predate eusociality, while several facultatively social, and solitary bee species possessed those bacterial taxa. Indeed, nearly all bee species displayed a range of affinities for single or multiple variants of the "socially associated" bacterial taxa, which unexpectedly demonstrated high sequence variation. CONCLUSIONS: Taken together, these results call into question whether specific bacterial associates facilitate eusocial behavior, or are subsequently adopted, or indicate frequent horizontal transmission between perennial eusocial colonies and other social, facultatively social, and solitary bees. Video Abstract.