Host Microbiota Research Articles

Early feeding leads to molecular maturation of the gut mucosal immune system in suckling piglets.

Diet-microbiota-host interactions are increasingly studied to comprehend their implications in host metabolism and overall health. Keeping in mind the importance of early life programming in shaping intestinal mucosal development, the pre-weaning period can be utilised to understand these interactions in suckling piglets. The objective of this study was to investigate the consequences of early life feeding on the time-resolved mucosal transcriptional program as well as mucosal morphology. A customised fibrous feed was provided to piglets (early-fed or EF group; 7 litters) from five days of age until weaning (29 days of age) in addition to sow's milk, whereas control piglets (CON; 6 litters) suckled mother's milk only. Rectal swabs, intestinal content, and mucosal tissues (jejunum, colon) were obtained pre- and post-weaning for microbiota analysis (16S amplicon sequencing) and host transcriptome analysis (RNA sequencing). Early feeding accelerated both microbiota colonisation as well as host transcriptome, towards a more "mature state", with a more pronounced response in colon compared to jejunum. Early feeding elicited the largest impact on the colon transcriptome just before weaning (compared to post-weaning time-points), exemplified by the modulation of genes involved in cholesterol and energy metabolism and immune response. The transcriptional impact of early feeding persisted during the first days post-weaning and was highlighted by a stronger mucosal response to the weaning stress, via pronounced activation of barrier repair reactions, which is a combination of immune activation, epithelial migration and "wound-repair" like processes, compared to the CON piglets. Our study demonstrates the potential of early life nutrition in neonatal piglets as a means to support their intestinal development during the suckling period, and to improve adaptation during the weaning transition.

Emerging roles of host and microbial bioactive lipids in inflammatory bowel diseases.

The intestinal tract harbors diverse microorganisms, host- and microbiota-derived metabolites, and potentially harmful dietary antigens. The epithelial barrier separates the mucosa, where diverse immune cells exist, from the lumen to avoid excessive immune reactions against microbes and dietary antigens. Inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease, is characterized by a chronic and relapsing disorder of the gastrointestinal tract. Although the precise etiology of IBD is still largely unknown, accumulating evidence suggests that IBD is multifactorial, involving host genetics and microbiota. Alterations in the metabolomic profiles and microbial community are features of IBD. Advances in mass-spectrometry-based lipidomic technologies enable identification of changes in the composition of intestinal lipid species in IBD. Because lipids have a wide range of functions, including signal transduction and cell membrane formation, dysregulation of lipid metabolism drastically affects the physiology of the host and microorganisms. Therefore, a better understanding of the intimate interactions of intestinal lipids with host cells that are implicated in the pathogenesis of intestinal inflammation might aid in the identification of novel biomarkers and therapeutic targets for IBD. This review summarizes the current knowledge on the mechanisms by which host and microbial lipids control and maintain intestinal health and diseases. This article is protected by copyright. All rights reserved.

Crosstalk between ILC3s and Microbiota: Implications for Colon Cancer Development and Treatment with Immune Check Point Inhibitors.

Type 3 innate lymphoid cells (ILC3s) are primarily tissue-resident cells strategically localized at the intestinal barrier that exhibit the fast-acting responsiveness of classic innate immune cells. Populations of these lymphocytes depend on the transcription factor RAR-related orphan receptor and play a key role in maintaining intestinal homeostasis, keeping host-microbial mutualism in check. Current evidence has indicated a bidirectional relationship between microbiota and ILC3s. While ILC3 function and maintenance in the gut are influenced by commensal microbiota, ILC3s themselves can control immune responses to intestinal microbiota by providing host defense against extracellular bacteria, helping to maintain a diverse microbiota and inducing immune tolerance for commensal bacteria. Thus, ILC3s have been linked to host-microbiota interactions and the loss of their normal activity promotes dysbiosis, chronic inflammation and colon cancer. Furthermore, recent evidence has suggested that a healthy dialog between ILC3s and gut microbes is necessary to support antitumor immunity and response to immune checkpoint inhibitor (ICI) therapy. In this review, we summarize the functional interactions occurring between microbiota and ILC3s in homeostasis, providing an overview of the molecular mechanisms orchestrating these interactions. We focus on how alterations in this interplay promote gut inflammation, colorectal cancer and resistance to therapies with immune check point inhibitors.

The Interplay between Gut Microbiota and Oral Medications and Its Impact on Advancing Precision Medicine.

Trillions of diverse microbes reside in the gut and are deeply interwoven with the human physiological process, from food digestion, immune system maturation, and fighting invading pathogens, to drug metabolism. Microbial drug metabolism has a profound impact on drug absorption, bioavailability, stability, efficacy, and toxicity. However, our knowledge of specific gut microbial strains, and their genes that encode enzymes involved in the metabolism, is limited. The microbiome encodes over 3 million unique genes contributing to a huge enzymatic capacity, vastly expanding the traditional drug metabolic reactions that occur in the liver, manipulating their pharmacological effect, and, ultimately, leading to variation in drug response. For example, the microbial deactivation of anticancer drugs such as gemcitabine can lead to resistance to chemotherapeutics or the crucial role of microbes in modulating the efficacy of the anticancer drug, cyclophosphamide. On the other hand, recent findings show that many drugs can shape the composition, function, and gene expression of the gut microbial community, making it harder to predict the outcome of drug-microbiota interactions. In this review, we discuss the recent understanding of the multidirectional interaction between the host, oral medications, and gut microbiota, using traditional and machine-learning approaches. We analyze gaps, challenges, and future promises of personalized medicine that consider gut microbes as a crucial player in drug metabolism. This consideration will enable the development of personalized therapeutic regimes with an improved outcome, ultimately leading to precision medicine.

107 Meta-Analysis of Clinical and Preclinical Microbiome Data from Studies of Burn Injury

Abstract Introduction Following burn injury, the ecology of the host microbiota is disrupted to varying degrees and may leave the patient susceptible to opportunistic pathogens or disrupt the endogenous flora needed to potentiate recovery and homeostasis. Studies examining the microbiome post-burn injury usually have a limited sample size which, coupled with experimental and analysis variation, impacts overall interpretation of data. Methods We performed a meta-analysis of publicly available sequencing data from burn patients and burn animals to determine if there were consistent alterations in the microbiome across various anatomical sites and species. A MEDLINE search was used to identify applicable publications. Corresponding authors of papers without available data were contacted, and data were used if a response occurred. Ten human and animal 16S rRNA sequencing studies spanning respiratory, urinary, cutaneous, and gastrointestinal microbiomes were included. Raw sequencing data were systematically analyzed with taxonomic classification and α and β diversity metrics generated. Results Alpha diversity was consistently lower post-burn, except for human skin (Figure 1) due to perianal skin sampling of burn patients resulting in higher species richness than controls. Weighted UniFrac distance analysis showed that rodent specimens clustered less closely to humans than pig samples (P < 0.0001) for both rectal and skin samples. Host species (R2 = 0.21, P = 0.001), and institute (R2 = 0.35, P = 0.001) had a significant impact on the β diversity. In rectal samples, bacterial composition in pig and human burn samples included Bacteroidetes, Firmicutes, and Proteobacteria, while rodent samples were dominated by over 90% Firmicutes. Burns induced an increase of Proteobacteria and a decrease in Bacteroidetes and Firmicutes in pig rectal samples. Proteobacteria and Firmicutes increased on burned skin in each host species. Longitudinal studies revealed a decrease in α diversity upon burn injury with β diversity and taxa shifts. Conclusions Overall, our results suggest that host species and the sequencing site strongly influence microbiome structure. Burn-induced alterations in microbiome diversity and taxa exist across hosts, with certain metrics more influenced by host. Applicability of Research to Practice Coordinated, multi-center studies, both clinical and pre-clinical, are needed to truly realize the diagnostic and therapeutic potential of the microbiome for improving outcomes post-burn.

The effects of host quantitative genetic architecture on the gut microbiota composition of Chinook salmon (Oncorhynchus tshawytscha).

The microbiota consists of microbes living in or on an organism and has been implicated in host health and function. Environmental and host-related factors were shown to shape host microbiota composition and diversity in many fish species, but the role of host quantitative architecture across populations and among families within a population is not fully characterized. Here, Chinook salmon were used to determine if inter-population differences and additive genetic variation within populations influenced the gut microbiota diversity and composition. Specifically, hybrid stocks of Chinook salmon were created by crossing males from eight populations with eggs from an inbred line created from self-fertilized hermaphrodite salmon. Based on high-throughput sequencing of the 16S rRNA gene, significant gut microbial community diversity and composition differences were found among the hybrid stocks. Furthermore, additive genetic variance components varied among hybrid stocks, indicative of population-specific heritability patterns, suggesting the potential to select for specific gut microbiota composition for aquaculture purposes. Determining the role of host genetics in shaping their gut microbiota has important implications for predicting population responses to environmental changes and will thus impact conservation efforts for declining populations of Chinook salmon.

Host Immunity and Immunization Strategies for Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) represents a significant challenge to public health. C. difficile-associated mortality and morbidity have led the U.S. CDC to designate it as an urgent threat. Moreover, recurrence or relapses can occur in up to a third of CDI patients, due in part to antibiotics being the primary treatment for CDI and the major cause of the disease. In this review, we summarize the current knowledge of innate immune responses, adaptive immune responses, and the link between innate and adaptive immune responses of the host against CDI. The other major determinants of CDI, such as C. difficile toxins, the host microbiota, and related treatments, are also described. Finally, we discuss the known therapeutic approaches and the current status of immunization strategies for CDI, which might help to bridge the knowledge gap in the generation of therapy against CDI.

Meta-omics profiling of the gut-lung axis illuminates metabolic networks and host-microbial interactions associated with elevated lung elastance in a murine model of obese allergic asthma.

Obesity and associated changes to the gut microbiome worsen airway inflammation and hyperresponsiveness in asthma. Obesogenic host-microbial metabolomes have altered production of metabolites that may influence lung function and inflammatory responses in asthma. To understand the interplay of the gut microbiome, metabolism, and host inflammation in obesity-associated asthma, we used a multi-omics approach to profile the gut-lung axis in the setting of allergic airway disease and diet-induced obesity. We evaluated an immunomodulator, nitro-oleic acid (NO2-OA), as a host- and microbial-targeted treatment intervention for obesity-associated allergic asthma. Allergic airway disease was induced using house dust mite and cholera toxin adjuvant in C57BL6/J mice with diet-induced obesity to model obesity-associated asthma. Lung function was measured by flexiVent following a week of NO2-OA treatment and allergen challenge. 16S rRNA gene (from DNA, taxa presence) and 16S rRNA (from RNA, taxa activity) sequencing, metabolomics, and host gene expression were paired with a Treatment-Measured-Response model as a data integration framework for identifying latent/hidden relationships with linear regression among variables identified from high-dimensional meta-omics datasets. Targeting both the host and gut microbiota, NO2-OA attenuated airway inflammation, improved lung elastance, and modified the gut microbiome. Meta-omics data integration and modeling determined that gut-associated inflammation, metabolites, and functionally active gut microbiota were linked to lung function outcomes. Using Treatment-Measured-Response modeling and meta-omics profiling of the gut-lung axis, we uncovered a previously hidden network of interactions between gut levels of amino acid metabolites involved in elastin and collagen synthesis, gut microbiota, NO2-OA, and lung elastance. Further targeted metabolomics analyses revealed that obese mice with allergic airway disease had higher levels of proline and hydroxyproline in the lungs. NO2-OA treatment reduced proline biosynthesis by downregulation of pyrroline-5-carboxylate reductase 1 (PYCR1) expression. These findings are relevant to human disease: adults with mild-moderate asthma and BMI ≥ 25 had higher plasma hydroxyproline levels. Our results suggest that changes to structural proteins in the lung airways and parenchyma may contribute to heightened lung elastance and serve as a potential therapeutic target for obese allergic asthma.

Sporadic type VI secretion in seventh pandemic Vibrio cholerae.

Vibrio cholerae is a pathogen that causes disease in millions of people every year by colonizing the small intestine and then secreting the potent cholera toxin. How the pathogen overcomes the colonization barrier created by the host's natural microbiota is, however, still not well understood. In this context, the type VI secretion system (T6SS) has gained considerable attention given its ability to mediate interbacterial killing. Interestingly, and in contrast to non-pandemic or environmental V. cholerae isolates, strains that are causing the ongoing cholera pandemic (7PET clade) are considered T6SS-silent under laboratory conditions. Since this idea was recently challenged, we performed a comparative in vitro study on T6SS activity using diverse strains or regulatory mutants. We show that modest T6SS activity is detectable in most of the tested strains under interbacterial competition conditions. The system's activity was also observed through immunodetection of the T6SS tube protein Hcp in culture supernatants, a phenotype that can be masked by the strains' haemagglutinin/protease. We further investigated the low T6SS activity within the bacterial populations by imaging 7PET V. cholerae at the single-cell level. The micrographs showed the production of the machinery in only a small fraction of cells within the population. This sporadic T6SS production was higher at 30 °C than at 37 °C and occurred independently of the known regulators TfoX and TfoY but was dependent on the VxrAB two-component system. Overall, our work provides new insight into the heterogeneity of T6SS production in populations of 7PET V. cholerae strains in vitro and provides a possible explanation of the system's low activity in bulk measurements.

Resilience of swine nasal microbiota to influenza A virus challenge in a longitudinal study

Influenza A virus (IAV) is an important contributing pathogen of porcine respiratory disease complex (PRDC) infections. Evidence in humans has shown that IAV can disturb the nasal microbiota and increase host susceptibility to bacterial secondary infections. Few, small-scale studies have examined the impact of IAV infection on the swine nasal microbiota. To better understand the effects of IAV infection on the nasal microbiota and its potential indirect impacts on the respiratory health of the host, a larger, longitudinal study was undertaken to characterize the diversity and community composition of the nasal microbiota of pigs challenged with an H3N2 IAV. The microbiome of challenged pigs was compared with non-challenged animals over a 6-week period using 16S rRNA gene sequencing and analysis workflows to characterize the microbiota. Minimal changes to microbial diversity and community structure were seen between the IAV infected and control animals the first 10 days post-IAV infection. However, on days 14 and 21, the microbial populations were significantly different between the two groups. Compared to the control, there were several genera showing significant increases in abundance in the IAV group during acute infection, such as Actinobacillus and Streptococcus. The results here highlight areas for future investigation, including the implications of these changes post-infection on host susceptibility to secondary bacterial respiratory infections.

Microbiome protection against Coccidioidesgrowth

Abstract During infection, the host utilizes multiple mechanisms to prevent colonization and dissemination. Protection begins at the surface, often via the commensal community found within our respiratory, skin, and intestinal tract. Microbiota disruption reduces the effectiveness of this protective barrier. Coccidioidomycosis, or Valley fever, is often misdiagnosed as community acquired bacterial pneumonia and treated with antibiotics that alter microbiota density and diversity. Commensal bacteria influence host immune responses to infection, and antibiotic treatment alters host immunity. A soil microbial antagonist related to Bacillus subtilis inhibits in vitro growth of Coccidioides through a clear zone of inhibition between fungi and bacteria. Whether host microbiota also inhibits Coccidioides is unknown. To assess if host microbiota has inhibition capabilities against Coccidioides, we performed two inhibition assays and measured Coccidioides growth area. A 50/50 inhibition assay was performed in which host microbiota and Coccidioides were placed in direct competition on agar plates. A spike in inhibition assay was performed where host microbiota was grown to 80% confluency, to mimic an established in vivo microbiome, before spiking in Coccidioides. Our data indicate that intestinal and respiratory host microbiome species inhibit Coccidioides growth. To assess if host microbiota depletion allows greater Coccidioides growth, in vitro antibiotic disc diffusion assays and in vivo treatments were performed. Our data suggests that host respiratory and intestinal commensals inhibit Coccidioides growth. Antibiotic treatment may kill protective host bacteria that creates a niche for Coccidioides invasion. Supported by grant VFR-19-633952 from University of California Office of the President.

Commensal probiotic provides long-term protection in a murine model of allergic lung disease by altering the host microbiota

Abstract The incidence of allergic diseases is increasing, with house dust mite allergy, afflicting up to 20% of the population in developed countries. House dust mites (HDM) are a common allergen that can be difficult to avoid and triggers allergic reactions, including wheezing and shortness of breath. Bacillus subtilis is a gut-associated commensal probiotic that can prevent murine HDM-induced allergic lung inflammation. We exposed C57Bl/6 mice to B. subtilis via oral gavage and challenged with intranasal HDM for up to 8 weeks. We found that pretreatment with B. subtilis was able to provide protection from eosinophil infiltration, measured in bronchial alveolar lavage fluid (BALF), for 3 weeks. This loss of protection correlated with an increase in the eosinophil chemoattractant CCL24 levels in the BALF and reduced abundance of the bacterial phylum Verrucomicorbiota in collected feces. Additionally, we found that B. subtilis treatment altered the bacterial composition by increasing the abundance of the bacteria phylum Bacteroidetes. These results support B. subtilis as a prophylactic for preventing allergic lung disease and highlights that protection can last up to 3 weeks. This work also expands our understanding of how B. subtilis mediates protection and that in addition to modifying the immune system, it is also altering the host microbiota. This work is supported by start-up funds and core facility outsourcing funds from Midwestern University.

Probiotics as Antibiotic Alternatives for Human and Animal Applications

Probiotics are live microorganisms recognized as natural candidates to substitute antibiotic substances, usually used to treat bacterial infections responsible for numerous human and animal diseases. Antibiotics are mostly prescribed for treating infections caused by bacteria. However, their excessive and inappropriate use has resulted in the increase of bacterial antimicrobial resistance (AMR) and host microbiota imbalance or dysbiosis phenomena. Even though antibiotics are the most well-known lifesaving substances, the AMR within the bacterial community has become a growing threat to global health, with the potential to cause millions of deaths each year in the future. Faced with these worldwide issues, it is high time to discover and develop antibiotic alternatives. There exists some evidence of probiotic roles in antagonizing pathogens, modulating immune systems, and maintaining general host health by restoring the gut microbiota balance. The multi-antimicrobial action mechanisms of such beneficial living microorganisms are one approach to practicing the “prevention is better than cure” concept to avoid antibiotics. The current review proposes a comprehensive description of antibiotic-related AMR issues and the potential of probiotics as antibiotic alternatives, while discussing pros and cons, as well as some evidence of beneficial uses of probiotics for human and animal health protection through recent results of experimental models and clinical trials.

Interactions of Nanomaterials with Gut Microbiota and Their Applications in Cancer Therapy.

Cancer treatment is a challenge by its incredible complexity. As a key driver and player of cancer, gut microbiota influences the efficacy of cancer treatment. Modalities to manipulate gut microbiota have been reported to enhance antitumor efficacy in some cases. Nanomaterials (NMs) have been comprehensively applied in cancer diagnosis, imaging, and theranostics due to their unique and excellent properties, and their effectiveness is also influenced by gut microbiota. Nanotechnology is capable of targeting and manipulating gut microbiota, which offers massive opportunities to potentiate cancer treatment. Given the complexity of gut microbiota-host interactions, understanding NMs-gut interactions and NMs-gut microbiota interactions are important for applying nanotechnologies towards manipulating gut microbiota in cancer prevention and treatment. In this review, we provide an overview of NMs-gut interactions and NMs-gut microbiota interactions and highlight the influences of gut microbiota on the diagnosis and treatment effects of NMs, further illustrating the potential of nanotechnologies in cancer therapy. Investigation of the influences of NMs on cancer from the perspective of gut microbiota will boost the prospect of nanotechnology intervention of gut microbiota for cancer therapy.

Effects of Polyunsaturated Fatty Acids on Human Health Through Intestinal Microbiota

Unsaturated fatty acids act a necessary part in the intestinal health of the host microbiota environment and immune ability by being transformed by intestinal microorganisms. Polyunsaturated fatty acids (PUFAs) are very important to the host body, also they influence many physiological activities of the body. The amount of polyunsaturated fatty acids synthesized by the human body cannot meet the daily needs of the human body, and it is necessary to obtain some essential fatty acids (EFA) from food. At the same time, some intestinal microorganisms can also synthesize and convert polyunsaturated fatty acids, which contribute to the regulation and control of host immunity. In addition, PUFAs are also beneficial to humans. They are critical in sustaining a healthy and stable gut microbiota environment and regulating and controlling host immunity. This paper summarized the conversion mechanism and effect of intestinal microbiota on polyunsaturated fatty acids, discussed whether polyunsaturated fatty acids can regulate human diseases and microbiota as health products, and determined the regulatory mechanism of polyunsaturated fatty acids.

Integrated Omic Analysis of Human Plasma Metabolites and Microbiota in a Hypertension Cohort

Hypertension is closely related to metabolic dysregulation, which is associated with microbial dysbiosis and altered host–microbiota interactions. However, plasma metabolite profiles and their relationships to oral/gut microbiota in hypertension have not been evaluated in depth. Plasma, saliva, subgingival plaques, and feces were collected from 52 hypertensive participants and 24 healthy controls in a cross-sectional cohort. Untargeted metabolomic profiling of plasma was performed using high-performance liquid chromatography–mass spectrometry. Microbial profiling of oral and gut samples was determined via 16S rRNA and metagenomic sequencing. Correlations between metabolites and clinic parameters/microbiota were identified using Spearman’s correlation analysis. Metabolomic evaluation showed distinct clusters of metabolites in plasma between hypertensive participants and control participants. Hypertensive participants had six significantly increased and thirty-seven significantly decreased plasma metabolites compared to controls. The plasma metabolic similarity significantly correlated with the community similarity of microbiota. Both oral and gut microbial community composition had significant correlations with metabolites such as Sphingosine 1-phosphate, a molecule involved in the regulation of blood pressure. Plasma metabolites had a larger number of significant correlations with bacterial genera than fungal genera. The shared oral/gut bacterial genera had more correlations with metabolites than unique genera but shared fungal genera and metabolites did not show clear clusters. The hypertension group had fewer correlations between plasma metabolites and bacteria/fungi than controls at species level. The integrative analysis of plasma metabolome and oral/gut microbiome identified unreported alterations of plasma metabolites in hypertension and revealed correlations between altered metabolites and oral/gut microbiota. These observations suggested metabolites and microbiota may become valuable targets for therapeutic and preventive interventions of hypertension.

Body Size Poorly Predicts Host-Associated Microbial Diversity in Wild Birds.

The composition and diversity of avian microbiota are shaped by many factors, including host ecologies and environmental variables. In this study, we examine microbial diversity across 214 bird species sampled in Malawi at five major body sites: blood, buccal cavity, gizzard, intestinal tract, and cloaca. Microbial community dissimilarity differed significantly across body sites. Ecological theory predicts that as area increases, so does diversity. We tested the hypothesis that avian microbiota diversity is correlated with body size, used as a proxy for area, using comparative phylogenetic methods. Using Pagel's lambda, we found that few microbial diversity metrics had significant phylogenetic signals. Phylogenetic generalized least squares identified a significant but weak negative correlation between host size and microbial diversity of the blood and a similarly significant but weakly positive correlation between the cloacal microbiota and host size among birds within the order Passeriformes. Phylosymbiosis, or a congruent branching pattern between host phylogeny and their associated microbiota similarity, was tested and found to be weak or not significant in four of the body sites with sufficient sample size (blood, buccal, cloaca, and intestines). Taken together, these results suggest that the avian microbiome is highly variable, with microbiota diversity demonstrating few clear associations with bird size. Finally, the blood microbiota have a unique relationship with host size. IMPORTANCE All animals coexist and interact with microorganisms, including bacteria, archaea, microscopic eukaryotes, and viruses. These microorganisms can have an enormous influence on the biology and health of macro-organisms. However, the general rules that govern these host-associated microbial communities are poorly described, especially in wild animals. In this paper, we investigate the microbial communities of over 200 species of birds from Malawi and characterize five body site bacterial microbiota in depth. Because the evolutionary relationships of the host underlie the relationship between any host-associated microbiota relationships, we use phylogenetic comparative methods to account for this relationship. We find that the size of a host (the bird) and the diversity and composition of the microbiota are largely uncorrelated. We also find that the general pattern of similarity between host phylogeny and microbiota similarity is weak. Together, we see that bird microbiota are not strongly tied to host size or evolutionary history.

Size matters either way: Differently-sized microplastics affect amphibian host and symbiotic microbiota discriminately

Concerns about the implications of microplastics (MPs) on aqueous animals have gained widespread attention. It has been postulated that the magnitude of MPs can influence its toxicity. However, little is known about how MPs toxicity changes with particle size. Amphibians are reliable bioindicators of ecosystem health due to their complex life cycles. In this study, we compared the influences of two sizes nonfunctionalized polystyrene microspheres (1 and 10 μm) on the metamorphosis of Asiatic toad (Bufo gargarizans). Acute exposure to MPs at high concentrations led to bioaccumulation in the digestive track and internal organs (i.e., liver and heart) of tadpoles. Long-term exposure to either size, at environmentally-related concentrations (1 and 4550 p/mL), led to growth and development delay in pro-metamorphic tadpoles. Remarkably, developmental plasticity mitigated these deleterious effects prior to the onset of metamorphic climax without compromising survival rate in later stages. MPs with a diameter of 10 μm dramatically altered the gut microbiota (e.g., abundance of Catabacter and Desulfovibrio) of pro-metamorphic tadpoles, whereas MPs with a diameter of 1 μm induced much more intensive transcriptional responses in the host tissues (e.g., upregulation of protein synthesis and mitochondrial energy metabolism, and downregulation of neural functions and cellular responses). Given that the two MPs sizes induced similar toxic outcomes, this suggests that their principal toxicity mechanisms are distinct. Small-sized MPs can travel easily across the intestinal mucosa and cause direct toxicity, while large-sized MPs accumulate in gut and affect the host by changing the homeostasis of digestive track. In conclusion, our findings indicate that MPs can affect the growth and development of amphibian larvae, but their developmental plasticity determines the ultimate detrimental effects. Multiple pathways of toxicity may contribute to the size-dependent toxicity of MPs. We anticipate that these findings will increase our understanding of the ecological effects of MPs.

Mulberry leaf water extract alleviates type 2 diabetes in mice via modulating gut microbiota-host co-metabolism of branched-chain amino acid.

Elevations in circling branched-chain amino acids (BCAAs) levels associated with insulin resistance and type 2 diabetes mellitus (T2DM). Morus alba L. water extracts (MLE) show hypoglycemic function, but the precise mechanism remains obscure. This study is designed to investigate the association of the antidiabetes effect of MLE with the BCAAs co-metabolism modulated by host and gut microbiota. Tissue-specific expressions of BCAA-catabolizing enzymes were detected by RT-PCR and western blot, respectively. The components of the intestinal microflora were analyzed by high-throughput 16S rRNA gene sequencing. The results showed that MLE administration improved blood glucose and insulin level, decreased inflammatory cytokines expression, and lowered serum and feces BCAAs levels. Furthermore, MLE reversed the abundance changes of the bacterial genera correlated with serum and feces BCAAs, such as Anaerovorax, Bilophila, Blautia, Colidextribacter, Dubosiella, Intestinimonas, Lachnoclostridium, Lachnospiraceae_NK4A136, Oscillibacter, and Roseburia. Functionality prediction indicated that MLE potentially inhibited bacterial BCAAs biosynthesis, and promoted the tissue-specific expression of BCAAs catabolic enzyme. More importantly, MLE had obvious impacts on BCAA catabolism in germ-free-mimic T2DM mice. Those results indicated that MLE improving T2DM-related biochemical abnormalities is associated with not only gut microbiota modification but also the tissue-specific expression of BCAAs catabolic enzyme.

Genome-resolving metagenomics reveals wild western capercaillies (Tetrao urogallus) as avian hosts for antibiotic-resistance bacteria and their interactions with the gut-virome community

The gut microbiome is a critical component of avian health, influencing nutrient uptake and immune functions. While the gut microbiomes of agriculturally important birds have been studied, the microbiomes of wild birds still need to be explored. Filling this knowledge gap could have implications for the microbial rewilding of captive birds and managing avian hosts for antibiotic-resistant bacteria (ARB). Using genome-resolved metagenomics, we recovered 112 metagenome-assembled genomes (MAGs) from the faeces of wild and captive western capercaillies (Tetrao urogallus) (n = 8). Comparisons of bacterial diversity between the wild and captive capercaillies suggest that the reduced diversity in the captive individual could be due to differences in diet. This was further substantiated through the analyses of 517,657 clusters of orthologous groups (COGs), which revealed that gene functions related to amino acids and carbohydrate metabolisms were more abundant in wild capercaillies. Metagenomics mining of resistome identified 751 antibiotic resistance genes (ARGs), of which 40.7 % were specific to wild capercaillies suggesting that capercaillies could be potential reservoirs for hosting ARG-associated bacteria. Additionally, the core resistome shared between wild and captive capercaillies indicates that birds can acquire these ARG-associated bacteria naturally from the environment (43.1 % of ARGs). The association of 26 MAGs with 120 ARGs and 378 virus operational taxonomic units (vOTUs) also suggests a possible interplay between these elements, where putative phages could have roles in modulating the gut microbiota of avian hosts. These findings can have important implications for conservation and human health, such as avian gut microbiota rewilding, identifying the emerging threats or opportunities due to phage-microbe interactions, and monitoring the potential spread of ARG-associated bacteria from wild avian populations.