Host Health Research Articles

Proteomic analysis of mouse liver lesions at all three stages of Echinococcus granulosus infection.

Echinococcus granulosus, a zoonotic parasite, can severely damage host health or even lead to host death. In humans, early diagnosis of E. granulosus infection is difficult because the initial stages of the infection tend to be asymptomatic, this delays treatment and worsens prognosis in most patients. Herein, we present a comprehensive, temporal proteomic atlas of the liver at three stages of E. granulosus infection and analyze the changes in the proteome of host focal lesions; this atlas may provide an overview of the effects of E. granulosus in the host, as well as the interactions between them. We identified 3,197 proteins from mice model at 1, 3, and 6 months after E. granulosus infection; of these proteins, 760 were differentially expressed (520 upregulated; 240 downregulated). Moreover, 228 differentially expressed proteins were screened through cluster analysis and classified into four clusters according to their changing trends. Subsequently, candidate molecules related to cyst invasion, growth, candidate pathways and proteins related to angiogenesis were noted to demonstrate important value in mouse liver. Next, we used western blotting to verify the presence of the aforementioned proteins in mouse liver. In the later stages, E. granulosus infection was noted to result in significant enrichment of crucial proteins facilitating protoscoleces growth and development and inhibition of amino acid and lipid metabolic enzyme expression in mouse liver; it was also noted to transform host metabolism by weakening oxidative phosphorylation and enhancing glycolysis. In conclusion, we explored the molecular mechanisms underlying the parasitic processes of E. granulosus through proteomic analysis. Our results provide evidence that may enable the exploration of core regulatory targets for early and effective diagnosis and immunotherapy of E. granulosus infection, as well as parasite-host interactions involved in cystic echinococcosis development.

Akkermansia muciniphila: A promising probiotic against inflammation and metabolic disorders.

Metabolic disease is a worldwide epidemic that has become a public health problem. Gut microbiota is considered to be one of the important factors that maintain human health by regulating host metabolism. As an abundant bacterium in the host gut, A. muciniphila regulates metabolic and immune functions, and protects gut health. Multiple studies have indicated that alterations in the abundance of A. muciniphila are associated with various diseases, including intestinal inflammatory diseases, obesity, type 2 diabetes mellitus, and even parasitic diseases. Beneficial effects were observed not only in live A. muciniphila, but also in pasteurized A. muciniphila, A. muciniphila-derived extracellular vesicles, outer membrane, and secreted proteins. Although numerous studies have only proven the simple correlation between multiple diseases and A. muciniphila, an increasing number of studies in animal models and preclinical models have demonstrated that the beneficial impacts shifted from correlations to in-depth mechanisms. In this review, we provide a comprehensive view of the beneficial effects of A. muciniphila on different diseases and summarize the potential mechanisms of action of A. muciniphila in the treatment of diseases. We provide a comprehensive understanding of A. muciniphila for improving host health and discuss the perspectives of A. muciniphila in the future studies.

Investigation of gut microbiota composition in humans carrying blastocystis subtypes 1 and 2 and Entamoeba hartmanni

The composition of human gut microbiota is dominated by bacteria which have been extensively studied. The role of intestinal eukaryote microorganisms like Blastocystis, however, remains under investigation. Moreover, the potential impact on gut health related to Blastocystis presence was primarily investigated in symptomatic individuals mainly from industrialized countries, and appears to be mostly beneficial to the host microbiota. Data from surveys conducted in underdeveloped countries with higher prevalence and from asymptomatic individuals could therefore be valuable. The aim of this preliminary study was to analyze the composition of the gut microbiota in relation to the protozoa Blastocystis ST1 and ST2 and Entamoeba hartmanni carriage in asymptomatic subjects living in a semi-urban area of Côte d’Ivoire to add data into the ongoing debate on the role of Blastocystis in host health. The amplification of the V3 and V4 regions of bacterial 16S rDNA genes was performed to obtain the gut microbiota composition, and differential analyses on alpha and beta diversity were performed from the phylum to genus taxonomic level. The analysis revealed that individuals positive for both protozoa exhibited higher alpha and beta diversity compared to those who tested negative. Additionally, their bacterial composition showed a reduction in Bacteroides and an increase in Prevotella 9. Relative abundances of some OTUs, particularly Faecalibacterium, observed in individuals who tested positive for protozoa, were correlated with a good state of health of the gut microbiota. Blastocystis ST1 and ST2 associated with E. hartmanni thus appeared to be related to a state of intestinal eubiosis.

Draft genome of a human gut-derived Blautia sp. that ameliorates colitis and colitis-associated sociability deficits in mice.

Blautia is a genus of anaerobic, gram-positive bacteria commonly found in mammalian gastrointestinal tracts. Yet, how variations among different Blautia strains can impact host health is poorly understood. We present a Blautia sp. genome isolated from human feces whose supplementation to mice can ameliorate colitis severity and associated sociability deficits.

A study protocol for a multi-country cluster randomized controlled trial of the impact of a multi-component One Health strategy to eliminate Opisthorchis viverrini and soil transmitted helminths in the Lower Mekong Basin

BackgroundOpisthorchis viverrini (OV) and soil-transmitted helminths (STH) are two of the most common helminths contributing to the Neglected Tropical Disease (NTDs) burden in the Lower Mekong Basin. Although mass drug administration is the cornerstone of control programs to reduce morbidity caused by these infections, this approach has limitations in preventing re-infections. Elimination requires additional measures such as reservoir host treatment, improved hygiene and health education to reinforce MDA's impact. This study aims to examine the impact of a scalable multi-component One Health Helminth Elimination program in the Lower Mekong Basin (HELM) that combines human praziquantel (PZQ) and albendazole (ALB) treatment with a program that includes the “Magic Glasses” and the “Lawa Model” interventions with health promotion at their core.MethodsThis study will employ a cluster randomized controlled trial (cRCT) in 18 rural communities (with sub-district or villages as cluster units) across Cambodia, Laos and Thailand. The control arm will receive one round of PZQ/ALB treatment, while in the intervention arm, multi-component HELM program will be implemented, which includes PZQ/ALB treatment together with the Magic Glasses and Lawa Model interventions. OV and STH infections levels will be evaluated in individuals aged 5–75 years at baseline and will be repeated at follow-up (12 months after the HELM intervention), using modified formalin ethyl-acetate concentration technique and quantitative PCR. The primary outcome of the study will be cumulative incidence of human OV and STH infections. Outcomes between the study arms will be compared using generalized linear mixed models, accounting for clustering.DiscussionEvidence from this trial will quantify the impact of a multi-component One Health control strategy in interrupting Ov and STH infections in the Lower Mekong Basin.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622000353796. Prospectively registered 28 February 2022.

Gut microbiome and NAFLD: impact and therapeutic potential

Non-Alcoholic Fatty Liver Disease (NAFLD) affects approximately 32.4% of the global population and poses a significant health concern. Emerging evidence underscores the pivotal role of the gut microbiota—including bacteria, viruses, fungi, and parasites—in the development and progression of NAFLD. Dysbiosis among gut bacteria alters key biological pathways that contribute to liver fat accumulation and inflammation. The gut virome, comprising bacteriophages and eukaryotic viruses, significantly shapes microbial community dynamics and impacts host metabolism through complex interactions. Similarly, gut fungi maintain a symbiotic relationship with bacteria; the relationship between gut fungi and bacteria is crucial for overall host health, with certain fungal species such as Candida in NAFLD patients showing detrimental associations with metabolic markers and liver function. Additionally, the “hygiene hypothesis” suggests that reduced exposure to gut parasites may affect immune regulation and metabolic processes, potentially influencing conditions like obesity and insulin resistance. This review synthesizes current knowledge on the intricate interactions within the gut microbiota and their associations with NAFLD. We highlight the therapeutic potential of targeting these microbial communities through interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Addressing the complexities of NAFLD requires comprehensive strategies that consider the multifaceted roles of gut microorganisms in disease pathology.

The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function

The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic–pituitary–adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.

Invasive Fascioloides magna infections impact gut microbiota in a definitive host in Europe

Invasive parasites that expand their natural range can be a threat to wildlife biodiversity and may pose a health risk to non-adapted, naive host species. The invasive giant liver fluke, Fascioloides magna, native to North America, has extended its range in Europe and uses mainly red deer (Cervus elaphus) as definitive hosts. The penetration of the intestinal barrier by the young flukes to reach the liver via the abdominal cavity as well as the release of fluke metabolism products and excreta with the bile and/or changes in the microbial community of the biliary system may enable the translocation of intestinal bacteria across the intestinal barrier and, in turn, could be associated with inflammation and changes in the intestinal bacterial community. The gut commensal community plays a key role in host nutrition and interacts with cells of the immune system to maintain host health. For this study, the gut bacterial community of red deer infected with F. magna and of non-infected red deer from one of the largest forest ecosystems in Central Europe, located on the border between the Czech Republic and Germany, was investigated. The individual fluke burden was associated with changes in the gut microbial composition of the gut of infected individuals, whereas the diversity and composition of the gut bacteria were only slightly different between fluke-infected and uninfected deer. Several bacterial taxa at the genus level were unique to individuals carrying either one or many liver flukes. Our results suggest that the microbiota of red deer is stable to perturbation by low numbers of F. magna. However, a larger parasite burden may cause changes in the gut microbial composition in definitive hosts implying that non-invasive fecal microbiome assessments could serve as indicator for wildlife health monitoring.

Effect of elite sport activity on salivary microbiota: The case of water polo

It has been well established that the human gut microbiota plays a pivotal role in humans' health, since it is involved in nutrients' uptake, vitamins' synthesis, energy harvest, inflammatory modulation, and host immune responses. Moreover, gut microbiota alterations have been associated to an increasing number of diseases and its composition can be affected by several factors, including physical exercise. In particular, it has been reported that intense physical activity can induce metabolic changes which translate in alterations of specific biomarkers that can lead to the onset of infections, inflammation and hepatic or kidney disorders. Recently, the oral microbiota has shown its relevance not only for the health of oral cavity but also for human host's health, emerging as an ecological niche with a great potential for the study of gut microbiome alterations due also to its accessibility respect to other tracts that can be inferred through fecal samples analysis. Thus, the purpose of this study has been to assess the effect of intense physical activity, i.e., elite water polo, on the human salivary microbiota. Thirteen professional water polo players and nineteen sedentary controls were recruited for this study. The salivary microbiota analysis was performed in oral rinse collected from both controls and athletes three months after the beginning of the agonist season. Our results showed significant differences in the salivary microbiota between athletes and controls. In particular, three species, namely Oribacterium sinus, Oribacterium parvum and Oribacterium asaccharolyticum, were found to be significantly increased in the water polo players compared to controls. Even if these data have to be further validated, also to assess the role of these identified species, they strengthen the hypothesis that elite sports can influence and alter the status of the gut microbiota. Moreover, the saliva is confirmed as a suitable sample for microbiome evaluations that may improve athletes' status evaluation and monitoring.

Endogenous Viral Elements: insights into data availability and accessibility

Abstract Endogenous viral elements (EVEs) are remnants of viral genetic material endogenized into the host genome. They have, in the last decades, attracted attention for their role as potential contributors to pathogenesis, drivers of selective advantage for the host, and genomic remnants of ancient viruses. EVEs have a nuanced and complex influence on both host health and evolution, and can offer insights on the deep evolutionary history of viruses. As an emerging field of research, several factors limit a comprehensive understanding of EVEs: they are currently underestimated and periodically overlooked in studies of the host genome, transcriptome, and virome. The absence of standardized guidelines for ensuring EVE-related data availability and accessibility following the FAIR (‘findable, accessible, interoperable, and reusable’) principles obstructs our ability to gather and connect information. Here, we discuss challenges to the availability and accessibility of EVE-related data and propose potential solutions. We identified the biological and research focus imbalance between different types of EVEs, and their overall biological complexity as genomic loci with viral ancestry, as potential challenges that can be addressed with the development of a user-oriented identification tool. In addition, reports of EVE identification are scattered between different subfields under different keywords, and EVE sequences and associated data are not properly gathered in databases. While developing an open and dedicated database might be ideal, targeted improvements of generalist databases might provide a pragmatic solution to EVE data and metadata accessibility. The implementation of these solutions, as well as the collective effort by the EVE scientific community in discussing and setting guidelines, is now drastically needed to lead the development of EVE research and offer insights into host-virus interactions and their evolutionary history.

An Early-Life Disruption of Gut Microbiota Has Opposing Effects on Parasite Resistance in Two Host Species.

Gut microbiota regulate multiple aspects of host health, including metabolism and the development of the immune system. However, we still know relatively little about how the gut microbiota influences host responses to parasitism in wild organisms, particularly whether host-microbiota interactions contribute to variation in parasitism across host species. The goal of this study was to determine the role of gut microbiota in shaping how birds respond to nest parasites and investigate whether this relationship varies between host species. Both eastern bluebirds (Sialia sialis) and tree swallows (Tachycineta bicolor) are parasitized by blow flies (Protocalliphora sialia), for which larval flies feed on nestlings' blood. We experimentally manipulated the gut microbiota of nestling bluebirds and tree swallows by dosing nestlings with an oral antibiotic or sterile water as a control. We then quantified nestling physiology (haemoglobin, glucose, parasite-specific IgY antibody levels), body morphometrics, and survival until fledging, as well as blow fly abundance and size. An experimental disruption of nestling gut microbiota increased parasite abundance in tree swallows, but decreased parasite abundance in bluebirds, which suggests that the disruption has opposing effects on resistance across host species. Furthermore, experimental treatment delayed parasite development and had variable effects on nestling body morphometrics and physiology across the two host species. Together, these results suggest that gut microbiota contribute to host differences in resistance to blow flies and can influence host-parasite interactions.

The Parkinson’s disease drug entacapone disrupts gut microbiome homeostasis via iron sequestration

Many human-targeted drugs alter the gut microbiome, leading to implications for host health. However, the mechanisms underlying these effects are not well known. Here we combined quantitative microbiome profiling, long-read metagenomics, stable isotope probing and single-cell chemical imaging to investigate the impact of two widely prescribed drugs on the gut microbiome. Physiologically relevant concentrations of entacapone, a treatment for Parkinson’s disease, or loxapine succinate, used to treat schizophrenia, were incubated ex vivo with human faecal samples. Both drugs significantly impact microbial activity, more so than microbial abundance. Mechanistically, entacapone can complex and deplete available iron resulting in gut microbiome composition and function changes. Microbial growth can be rescued by replenishing levels of microbiota-accessible iron. Further, entacapone-induced iron starvation selected for iron-scavenging gut microbiome members encoding antimicrobial resistance and virulence genes. These findings reveal the impact of two under-investigated drugs on whole microbiomes and identify metal sequestration as a mechanism of drug-induced microbiome disturbance.

Research advancements on the diversity and host interaction of gut microbiota in chickens.

The maintenance of host health and immune function is heavily dependent on the gut microbiota. However, the precise contribution of individual microbial taxa to regulating the overall functionality of the gut microbiome remains inadequately investigated. Chickens are commonly used as models for studying poultry gut microbiota, with high-throughput 16S rRNA sequencing has emerged as a valuable tool for assessing both its composition and functionality. The interactions between the gut's microbial community and its host significantly influence health outcomes, disease susceptibility, and various mechanisms affecting gastrointestinal function. Despite substantial research efforts, the dynamic nature of this microbial ecosystem has led to inconsistencies in findings related to chicken gut microbiota, which is largely attributed to variations in rearing conditions. Consequently, the interaction between the chickens' gut microflora and its host remains inadequately explored. This review highlights recent advances in understanding these relationships, with a specific focus on microbial composition, diversity, functional mechanisms, and their potential implications for improving poultry production.

Parasite-gut microbiota associations in wild wood mice (Apodemus sylvaticus).

The mammalian gastrointestinal tract provides a habitat for multiple commensal and pathogenic organisms spanning all three domains of life. Both positive and negative interactions occur between gut inhabitants, with potential consequences for host health. Studies of parasite-microbiota associations in natural systems remain scarce, yet are important for understanding how parasite communities and commensal microbiota shape each other, and how these interactions influence host health. Here, we characterize associations between helminth and coccidial infections and gut microbiota profiles in a wild population of wood mice (Apodemus sylvaticus) over 3 years, using two complementary approaches. We first examined parasite-microbiota associations along the length of the gastrointestinal tract through destructive sampling. Then, in a larger non-invasive capture mark-recapture study, we assessed whether gut parasitic infections detected in feces predicted fecal microbiota diversity and composition. We found that while overall microbiota composition was not associated with infection by any common gut parasite species, microbiota richness was associated with gut parasitism in two ways: (i) infection by the trematode Corrigia vitta in the small intestine predicted higher microbiota diversity in the caecum; (ii) there was a negative relationship between gut parasite richness and fecal microbiota richness in the non-invasive study. As our results identified associations between gastrointestinal parasites and microbiota alpha diversity, a future experimental study in this tractable wild mammalian system would be valuable to definitively test the directionality of these interactions.

In Silico Analysis of Probiotic Bacteria Changes Across COVID-19 Severity Stages.

The gut microbiota plays a crucial role in modulating the immune response during COVID-19, with several studies reporting significant alterations in specific bacterial genera, including Akkermansia, Bacteroides, Bifidobacterium, Faecalibacterium, Lactobacillus, Oscillospira, and Ruminococcus. These genera are symbionts of the gut microbiota and contribute to host health. However, comparing results across studies is challenging due to differences in analysis methods and reference databases. We screened 16S rRNA raw datasets available in public databases on COVID-19, focusing on the V3-V4 region of the bacterial genome. In total, seven studies were included. All samples underwent the same bioinformatics pipeline, evaluating the differential abundance of these seven bacterial genera at each level of severity. The reanalysis identified significant changes in differential abundance. Bifidobacterium emerged as a potential biomarker of disease severity and a therapeutic target. Bacteroides presented a complex pattern, possibly related to disease-associated inflammation or opportunistic pathogen growth. Lactobacillus showed significant changes in abundance across the COVID-19 stages. On the other hand, Akkermansia and Faecalibacterium did not show significant differences, while Oscillospira and Ruminococcus produced statistically significant results but with limited relevance to COVID-19 severity. Our findings reveal new insights into the differential abundance of key bacterial genera in COVID-19, particularly Bifidobacterium and Bacteroides.

Excess mortality of infected ectotherms induced by warming depends on pathogen kingdom and evolutionary history.

Climate change is causing extreme heating events and leading to more infectious disease outbreaks, putting species persistence at risk. The extent to which warming temperatures and infection may together impair host health is unclear. Using a meta-analysis of >190 effect sizes representing 101 ectothermic animal host-pathogen systems, we demonstrate that warming significantly increased the mortality of hosts infected by bacterial pathogens. Pathogens that have been evolutionarily established within the host species showed higher virulence under warmer temperatures, too. Conversely, the effect of warming on novel infections-from pathogens without a shared evolutionary history with the host species-were more pronounced with larger differences between compared temperatures. We found that compared to established infections, novel infections were more deadly at lower/baseline temperatures. Moreover, we revealed that the virulence of fungal pathogens increased only when temperatures were shifted upwards towards the pathogen thermal optimum. The magnitude of all these significant effects was not impacted by host life-stage, immune complexity, pathogen inoculation methods, or exposure time. Overall, our findings reveal distinct patterns in changes of pathogen virulence during warming. We highlight the importance of pathogen taxa, thermal optima, and evolutionary history in determining the impact of global change on infection outcomes.

Gut microbial composition differs among FUNAAB Alpha broiler chicken genotypes raised in a tropical environment

The gut microbiota of FUNAAB Alpha chickens plays a crucial role in determining their overall health and performance. Understanding the various types and diversity of microbiota in the gut of different genotypes of chickens is crucial for enhancing their well-being, productivity, and disease resistance. This study employed 16S rRNA and metagenomics analysis to examine the gut bacteria of three genotypes of FUNAAB Alpha broiler chickens, namely Naked neck, Frizzle, and Normal feather. There were three phyla observed in the three genotypes: Bacteroidetes, Actinobacteria, and Firmicutes. Through the utilisation of 16S rRNA sequencing, we successfully identified and categorised the various microbiota present within the gastrointestinal tract. Our study revealed notable variations in the composition and quantity of microbiota across the three genotypes, suggesting that each genotype possesses a distinct collection of gut bacteria. A wide range of microbiological diversity was observed within the community. Interestingly, the Normal feather chicken exhibited a greater number of operational taxonomic units (OTUs) compared to the Naked neck and Frizzle feather chicken. This study presents significant findings regarding the ceacal microbiota of FUNAAB Alpha chickens, emphasising the variations observed among different genotypes. It is crucial to study composition-modification techniques to enhance host health and performance, as well as to control zoonotic pathogens that can contaminate poultry products and threaten consumers’ health.

Mapping Pesticide-Induced Metabolic Alterations in Human Gut Bacteria.

Pesticides can modulate gut microbiota (GM) composition, but their specific effects on GM remain largely elusive. Our study demonstrated that pesticides inhibit or promote growth in various GM species, even at low concentrations, and can accumulate in GM to prolong their presence in the host. Meanwhile, the pesticide induced changes in GM composition are associated with significant alterations in gut bacterial metabolism that reflected by the changes of hundreds of metabolites. We generated a pesticide-GM-metabolites (PMM) network that not only reveals pesticide-sensitive gut bacteria species but also report specific metabolic changes in 306 pesticide-GM pairs (PGPs). Using an in vivo mice model, we further demonstrated a PGP's interactions and verified the inflammation-inducing effects of pesticides on the host through dysregulated lipid metabolism of microbes. Taken together, our findings generate a PMM interactions atlas, and shed light on the molecular level of how pesticides impact host health by modulating GM metabolism.

F. prausnitzii potentially modulates the association between citrus intake and depression

BackgroundThe gut microbiome modulates the effects of diet on host health, but it remains unclear which specific foods and microbial features interact to influence risk of depression. To understand this interplay, we leveraged decades of dietary and depression data from a longitudinal cohort of women (n = 32,427), along with fecal metagenomics and plasma metabolomics from a substudy (n = 207) nested in this cohort, as well as an independent validation cohort of men (n = 307).ResultsWe report that citrus intake and its components are prospectively associated with a lower risk of depression and altered abundance of 15 gut microbial species, including enriched Faecalibacterium prausnitzii. In turn, we found a lower abundance of F. prausnitzii and its metabolic pathway, S-adenosyl-L-methionine (SAM) cycle I in participants with depression. To explore causality, we found that lower SAM production by F. prausnitzii may decrease intestinal monoamine oxidase A gene expression implicated in serotonin and dopamine synthesis.ConclusionsThese data underscore the role of diet in the prevention of depression and offer a plausible explanation for how the intestinal microbiome modulates the influence of citrus on mental health.ELPzvN5keGYhLtpEkepcjaVideo

Effect of calf separation on gut microbiome and fecal metabolome of mother in the captive Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis).

Social separation, or the absence of social support, can cause physical and psychological health issues. Social separation is crucial for the welfare of the Yangtze finless porpoise (YFP) in captivity because they face many challenges like frequent social separation, noise from visitors, and animal replacement, which can cause psychological and physiological stress. This research is aimed at assessing the potential negative impacts of social separation on the gut microbiome and metabolome of captive YFP, focusing on the potential imbalances caused by mother-calf separation. The study found that social separation did not alter the alpha and beta diversity of the gut microbes but increased the abundance of disease-associated taxa such as Romboutsia, Terrisporobacter, and Clostridium_sensu_stricto_13 in the MC (mother-calf) group while increasing Paeniclostridium and Clostridium_sensu_stricto_1 associated with host health in the MS (mother-separated) group. The fecal metabolome underwent significant changes during social separation, with stress-associated metabolites like kainic acid, phenethylamine glucuronide, and paxilline upregulated in the MC group and host health-associated metabolites like butyric acid, 6-hydroxyhexanoic acid, and fosinopril downregulated in the MS group. In addition, there was a strong association between the fecal microbiome and the metabolome of captive YFPs. The study enhances our comprehension of the detrimental effects of social separation, which result in disruptions in the gut microbiome and fecal metabolome. The study is aimed at introducing a new method for assessing the health and welfare of endangered mammals in captivity.