Microbiome Axis Research Articles

Lactobacillus Eats Amyloid Plaque and Post-Biotically Attenuates Senescence Due to Repeat Expansion Disorder and Alzheimer's Disease.

Patients with Alzheimer's disease and related dementia (ADRD) are faced with a formidable challenge of focal amyloid deposits and cerebral amyloid angiopathy (CAA). The treatment of amyloid deposits in ADRD by targeting only oxidative stress, inflammation and hyperlipidemia has not yielded significant positive clinical outcomes. The chronic high-fat diet (HFD), or gut dysbiosis, is one of the major contributors of ADRD in part by disrupted transport, epigenetic DNMT1 and the folate 1-carbon metabolism (FOCM) cycle, i.e., rhythmic methylation/de-methylation on DNA, an active part of epigenetic memory during genes turning off and on by the gene writer (DNMT1) and eraser (TET2/FTO) and the transsulfuration pathway by mitochondrial 3-mercaptopyruvate sulfur transferase (3MST)-producing H2S. The repeat CAG expansion and m6A disorder causes senescence and AD. We aim to target the paradigm-shift pathway of the gut-brain microbiome axis that selectively inhibits amyloid deposits and increases mitochondrial transsulfuration and H2S. We have observed an increase in DNMT1 and decreased FTO levels in the cortex of the brain of AD mice. Interestingly, we also observed that probiotic lactobacillus-producing post-biotic folate and lactone/ketone effectively prevented FOCM-associated gut dysbiosis and amyloid deposits. The s-adenosine-methionine (SAM) transporter (SLC25A) was increased by hyperhomocysteinemia (HHcy). Thus, we hypothesize that chronic gut dysbiosis induces SLC25A, the gene writer, and HHcy, and decreases the gene eraser, leading to a decrease in SLC7A and mitochondrial transsulfuration H2S production and bioenergetics. Lactobacillus engulfs lipids/cholesterol and a tri-directional post-biotic, folic acid (an antioxidant and inhibitor of beta amyloid deposits; reduces Hcy levels), and the lactate ketone body (fuel for mitochondria) producer increases SLC7A and H2S (an antioxidant, potent vasodilator and neurotransmitter gas) production and inhibits amyloid deposits. Therefore, it is important to discuss whether lactobacillus downregulates SLC25A and DNMT1 and upregulates TET2/FTO, inhibiting β-amyloid deposits by lowering homocysteine. It is also important to discuss whether lactobacillus upregulates SLC7A and inhibits β-amyloid deposits by increasing the mitochondrial transsulfuration of H2S production.

Integrated large-scale metagenome assembly and multi-kingdom network analyses identify sex differences in the human nasal microbiome.

Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections between men and women. It has been hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities. Here, we study the nasal microbiome of healthy young adults in the largest cohort to date with 1593 individuals, using shotgun metagenomic sequencing. We compile the most comprehensive reference catalog for the nasal bacterial community containing 4197 metagenome-assembled genomes and integrate the mycobiome, to provide a valuable resource and a more holistic perspective for the understudied human nasal microbiome. We systematically evaluate sex differences and reveal extensive sex-specific features in both taxonomic and functional levels in the nasal microbiome. Through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the female nasal microbiome compared to the male's. The analysis of the keystone bacteria reveals that the sex-dependent evolutionary characteristics might have contributed to these differences. In summary, we construct the most comprehensive catalog of metagenome-assembled-genomes for the nasal bacterial community to provide a valuable resource for the understudied human nasal microbiome. On top of that, comparative analysis in relative abundance and microbial co-occurrence networks identify extensive sex differences in the respiratory tract community, which may help to further our understanding of the observed sex disparities in the respiratory diseases.

Unravelling the Complexities and Recent Advances in the Management of Atopic Dermatitis

Abstract: Atopic dermatitis (AD) is a non-fatal, non-communicable, chronic skin inflammatory condition marked by itching, lesions, and skin barrier dysfunction. As per the International Eczema Council, as of 2022, more than 200 million people were suffering from AD, with the disease burden reported highest in children. Environmental factors, genetic predisposition, and lifestyle have been found to be essential factors in triggering the adverse skin response. In this review, we provide a detailed overview of the pathophysiology of AD, how the skin barrier gets altered from normal condition to AD, and the role of genetic defects in Filaggrin protein, affecting the skin barrier function by altering the skin pH and hydration. Also, we highlight the role of toll-like receptors (TLRs) and the altered skin and gut microbiota in inducing chronic inflammatory responses and playing a significant role in the pathogenesis of the disease. Further, we discuss the role of several chemokines and cytokines, which could serve as important prognosis markers for early detection, monitoring the disease progression, and assessing the response to the treatment. We also report the current treatment regime of multimodal therapeutics ranging from topical emollients to topical, oral, and injectable immune modulatory agents. Besides, we discuss the importance of the gut-skin microbiome axis and the increasingly important role of prebiotics in AD treatment.

Exploring the interplay between antiretroviral therapy and the gut-oral microbiome axis in people living with HIV

The gut and oral microbiome is altered in people living with HIV (PLWH). While antiretroviral treatment (ART) is pivotal in restoring immune function in PLWH, several studies have identified an association between specific antiretrovirals, particularly integrase inhibitors (INSTI), and weight gain. In our study, we explored the differences in the oral and gut microbiota of PLWH under different ART regimens, and its correlation to Body Mass Index (BMI). Fecal and salivary samples were collected from PLWH (n = 69) and healthy controls (HC, n = 80). We performed taxonomy analysis to determine the microbial composition and relationship between microbial abundance and ART regimens, BMI, CD4+T-cell count, CD4/CD8 ratio, and ART duration. PLWH showed significantly lower richness compared to HC in both the oral and gut environment. The gut microbiome composition of INSTI-treated individuals was enriched with Faecalibacterium and Bifidobacterium, whereas non-nucleotide reverse transcriptase inhibitor (NNRTI)-treated individuals were enriched with Gordonibacter, Megasphaera, and Staphylococcus. In the oral microenvironment, Veillonella was significantly more abundant in INSTI-treated individuals and Fusobacterium and Alloprevotella in the NNRTI-treated individuals. Furthermore, Bifidobacterium and Dorea were enriched in gut milieu of PLWH with high BMI. Collectively, our findings identify distinct microbial profiles, which are associated with different ART regimens and BMI in PLWH on successful ART, thereby highlighting significant effects of specific antiretrovirals on the microbiome.

Changes in the Bile Acid Pool and Timing of Female Puberty: Potential Novel Role of Hypothalamic TGR5.

The regulation of pubertal timing and reproductive axis maturation is influenced by a myriad of physiologic and environmental inputs yet remains incompletely understood. To contrast differences in bile acid isoform profiles across defined stages of reproductive maturity in humans and a rat model of puberty and to characterize the role of bile acid signaling via hypothalamic expression of bile acid receptor populations in the rodent model. Secondary analysis and pilot studies of clinical cohorts, rodent models, ex vivo analyses of rodent hypothalamic tissues. Bile acid concentrations is the main outcome measure. Lower circulatory conjugated:deconjugated bile acid concentrations and higher total secondary bile acids were observed in postmenarcheal vs pre-/early pubertal adolescents, with similar shifts observed in infantile (postnatal day [PN]14) vs early juvenile (PN21) rats alongside increased tgr5 receptor mRNA expression within the mediobasal hypothalamus of female rats. 16S rRNA gene sequencing of the rodent gut microbiome across postnatal life revealed changes in the gut microbial composition predicted to have bile salt hydrolase activity, which was observed in parallel with the increased deconjugated and increased concentrations of secondary bile acids. We show that TGR5-stimulated GnRH release from hypothalamic explants is mediated through kisspeptin receptors and that early overexpression of human-TGR5 within the arcuate nucleus accelerates pubertal onset in female rats. Bile acid isoform shifts along stages of reproductive maturation are conserved across rodents and humans, with preclinical models providing mechanistic insight for the neuroendocrine-hepatic-gut microbiome axis as a potential moderator of pubertal timing in females.

Meta-analysis of the gut-brain axis and mental disorder

The gut-brain axis refers to the bidirectional information communication network between the brain and the gut. Microbiome and gut-brain axis have been implicated in mental disorders and have become the focus of neuroscience research. A meta-analysis was conducted to summarize the evidence regarding this link. A filtering search was performed using Hollis, PubMed, and Google Scholar to identify considered studies and trials. A keyword search identified 5500 articles. Seven provided analytically valuable and eligible data and were finally included for consideration and analysis. The data offered relevant studies on depression or anxiety, Schizophrenia, and Alzheimer's disease. Of the seven papers, four used correlational analysis (n=952) on depression and anxiety, two (n=384) on Schizophrenia, and one (n=80) on Alzheimers disease. These correlation analyses were designed to investigate the differences in gut microbial abundance between normal individuals and patients with mental disorders. In addition, three studies (n=314) identified a causal link by comparing the changes in mental health status by altering or influencing the gut microbiota. These causal analyses aimed to explore the differences in gut microbial abundance before and after the onset of mental disorders. In this case, mental illnesses were 2.8 to 14 times higher in the experimental groups than in the control groups. The findings support the hypothesis that the health of the gut-brain axis (microbial abundance) is inversely correlated to the incidence of many psychological disorders. However, how the gut-brain axis facilitates the pathogenesis of mental disorders remains to be further studied.

The oral-gut microbiome axis in health and disease.

The human body hosts trillions of microorganisms throughout many diverse habitats with different physico-chemical characteristics. Among them, the oral cavity and the gut harbour some of the most dense and diverse microbial communities. Although these two sites are physiologically distinct, they are directly connected and can influence each other in several ways. For example, oral microorganisms can reach and colonize the gastrointestinal tract, particularly in the context of gut dysbiosis. However, the mechanisms of colonization and the role that the oral microbiome plays in causing or exacerbating diseases in other organs have not yet been fully elucidated. Here, we describe recent advances in our understanding of how the oral and intestinal microbiota interplay in relation to their impact on human health and disease.

The Human Microbiome and Mental Health: the Latest Views

Mental health is the emotional, psychological, and social well-being of a person who feels protected, needed, realizes his abilities, and can overcome life’s stresses. Mental disorders (MD) are a serious health problem worldwide today, which lead to a significant medical burden and economic losses for both medical institutions and patients and their families. Today, MD are one of the priority directions in the daily practice of Ukrainian doctors. MD can include anxiety, depression, bipolar disorder, autism spectrum disorder, schizophrenia, eating disorders, etc. Recently, the attention of scientists and doctors has been paid to the interaction between the microbiome and mental health. The researches which are aimed at defining what is a healthy microbiome have revealed significant individual differences in its composition and diversity. It has been established that a certain composition of the gut microbiome (GM) is associated with the development of anxiety disorders. Research results show that patients and animal models (mice) with anxiety disorders have a dramatic decrease in microbial richness and diversity. Patients with anxiety disorder typically had reduced Firmicutes and increased Bacteroidetes and Fusobacteria. In addition, GM changes were associated with the onset and development of depressive disorder. Differences in the composition of fecal microbiota in patients with major depressive disorder were revealed. The main methods of MD treatment today are pharmacotherapy and psychotherapy, which have limited effectiveness. However, practitioners are looking for alternative ways to help such patients. The results of many studies indicate that prebiotics (e.g., dietary fiber and alpha lactalbumin) as well as postbiotics show a protective effect on mental health, especially when used in combination. At the same time, prebiotics may be a potential agent for alleviating the side effects of antipsychotics used in the treatment of MD. More experimental researches and high-quality clinical trials are needed to study the effects of dietary components on MD through the brain–gut–microbiome axis.

The gut-airway microbiome axis in health and respiratory diseases.

Communication between the gut and remote organs, such as the brain or the cardiovascular system, has been well established and recent studies provide evidence for a potential bidirectional gut-airway axis. Observations from animal and human studies indicate that respiratory insults influence the activity of the gut microbiome and that microbial ligands and metabolic products generated by the gut microbiome shape respiratory immunity. Information exchange between these two large mucosal surface areas regulates microorganism-immune interactions, with significant implications for the clinical and treatment outcomes of a range of respiratory conditions, including asthma, chronic obstructive pulmonary disease and lung cancer. In this Review, we summarize the most recent data in this field, offering insights into mechanisms of gut-airway crosstalk across spatial and temporal gradients and their relevance for respiratory health.

The Oral-Lung Microbiome Axis in Connective Tissue Disease-Related Interstitial Lung Disease.

Connective tissue disease-related interstitial lung disease (CTD-ILD) is a frequent and serious complication of CTD, leading to high morbidity and mortality. Unfortunately, its pathogenesis remains poorly understood; however, one intriguing contributing factor may be the microbiome of the mouth and lungs. The oral microbiome, which is a major source of the lung microbiome through recurrent microaspiration, is altered in ILD patients. Moreover, in recent years, several lines of evidence suggest that changes in the oral and lung microbiota modulate the pulmonary immune response and thus may play a role in the pathogenesis of ILDs, including CTD-ILD. Here, we review the existing data demonstrating oral and lung microbiota dysbiosis and possible contributions to the development of CTD-ILD in rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus. We identify several areas of opportunity for future investigations into the role of the oral and lung microbiota in CTD-ILD.

Faecal hsa-miR-7704 inhibits the growth and adhesion of Bifidobacterium longum by suppressing ProB and aggravates hepatic encephalopathy

Both gut microbiome and microRNAs (miRNAs) play a role in the development of hepatic encephalopathy (HE). However, the functional link between the microbiome and host-derived miRNAs in faeces remains poorly understood. In the present study, patients with HE had an altered gut microbiome and faecal miRNAs compared with patients with chronic hepatitis B. Transferring faeces and faecal miRNAs from patients with HE to the recipient mice aggravated thioacetamide-induced HE. Oral gavage of hsa-miR-7704, a host-derived miRNA highly enriched in faeces from patients with HE, aggravated HE in mice in a microbiome-dependent manner. Mechanistically, hsa-miR-7704 inhibited the growth and adhesion of Bifidobacterium longum by suppressing proB. B. longum and its metabolite acetate alleviated HE by inhibiting microglial activation and ammonia production. Our findings reveal the role of miRNA–microbiome axis in HE and suggest that faecal hsa-miR-7704 are potential regulators of HE progression.

Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother's obesity as potentially environmental factors of ASD. The purpose of this review is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

Detailed Characterization of the Lung-Gut Microbiome Axis Reveals the Link between PD-L1 and the Microbiome in Non-Small-Cell Lung Cancer Patients.

Next-generation sequencing technologies have started a new era of respiratory tract research in recent years. Alterations in the respiratory microbiome between healthy and malignant conditions have been revealed. However, the composition of the microbiome varies among studies, even in similar medical conditions. Also, there is a lack of complete knowledge about lung-gut microbiome interactions in lung cancer patients. The aim of this study was to explore the lung-gut axis in non-small-cell lung cancer (NSCLC) patients and the associations between lung-gut axis microbiota and clinical parameters (CRP, NLR, LPS, CD8, and PD-L1). Lung tissue and fecal samples were used for bacterial 16S rRNA sequencing. The results revealed, for the first time, that the bacterial richness in lung tumor tissue gradually decreased with an increase in the level of PD-L1 expression (p < 0.05). An analysis of β-diversity indicated a significant positive correlation between the genera Romboutsia and Alistipes in both the lung tumor biopsies and stool samples from NSCLC patients (p < 0.05). Survival analysis showed that NSCLC patients with higher bacterial richness in their stool samples had prolonged overall survival (HR: 2.06, 95% CI: 1.025-4.17, p = 0.0426).

P1236 Oral microbiota dysbiosis in Inflammatory Bowel Disease patients

Abstract Background Recent data pointed that IBD is strictly related to gut microbiota although less is known about the connection between oral microbiota and IBD. It is also known that dysbiosis can lead to oral pathologies. Moreover, microbiome changes under therapeutic agents’ administration for IBD treatment have been described, including the identification of some bacteria as potential predictive markers for treatment effectiveness. The aim of our study was the quantification of salivary Firmicutes and Bacteroidetes in a cohort of IBD patients compared with a control group without IBD. Methods This was a collaborative transversal cohort study between an IBD consultation in a tertiary hospital and a faculty of dental medicine. Patients from IBD consultation were invited to participate and gave their informed consent. The exclusion criteria were the incapacity of mouth opening or give a written informed consent. Demographic and clinical data was collected. Oral health status was accessed to determine the periodontal diagnosis. Unstimulated saliva samples were collected before the oral examination for the quantification by quantitative real-time PCR. Statistical analysis was performed with SPSS 29.0 using Kruskal–Wallis H and Mann-Whitney U tests, and p values ≤ 0.05 were considered statistically significant. Results IBD patients presented an increased abundance of Firmicutes, both for UC (3.4 x10-5) and CD (4.9x10-5) as well as an increased abundance of Bacteroidetes for both UC (1.6 x10-5) and CD (1.4x10-5), when compared to the control group (figure 1). No significant differences were found between different treatments groups or no treatment (table 1) in abundance of Firmicutes and Bacteroidetes, respectively, of UC (p = 0.292 and p = 0.912) and CD (p=0.413 and p=0.254) patients. Additionally, no significant differences were found for Firmicutes and Bacteroidetes abundances, respectively, regarding: CD versus UC (p=0.600 and p=0.971), active disease and remission (based on a composite criterion for inactive disease considering HBI &amp;lt;5 for CD or a PMS ≤ 2 for UC, and FCP cut-off value of 150 mg/Kg), (p= 0.071 and p=0.242), smoking status (p=0.558 and p=0.488) and presence or absence of oral health (p=0.260 and p=0.556). Conclusion The oral microbiota characterization of IBD patients showed an elevated abundance of Firmicutes and Bacteroidetes when compared with healthy controls. These findings are valuable indicators of dysbiosis, emphasizing the intricate interplay between gut and oral microbiome in the context of inflammatory conditions. Future research is needed to clarify the oral-gut microbiome axis in IBD.

Gut microbiome and serum metabolome analyses identify Bacteroides fragilis as regulators of serotonin content and PRL secretion in broody geese

Broody behavior is regulated by hypothalamic prolactin secretion, which seriously affects egg production in poulty production. Numerous studies have provided evidence that animal behavior is governed by dynamic bidirectional communication between specific gut bacteria and their host via the brain–gut–microbiome axis. However, little research focused on how the gut microbiota influence broody behavior in poultry. In this study, Zhedong white geese in laying and brooding phases were selected. Ten differentially abundant bacteria in cecum were detected between brooding and laying geese through metagenomic analyses and 16S rRNA sequencing (P<0.05), and Bacteroides fragilis was specifically identified as a key driver species in the brooding geese. Moverover, the serum metabolites were quantified, and the 313 differentially abundant metabolites were found between the two groups of different physiological geese. They were primarily enriched in the tryptophan metabolism pathways. Pearson correlation analyses revealed there was a significant positive correlation between B. fragilis abundance and the context of 11 tryptophan metabolism-related metabolites (such as serotonin, etc.) in broody geese, which hinted that those tryptophan metabolites might be produced or driven by B. fragilis. Finally, the serum hormone levels were also measured. We found there was a positive correlation between B. fragilis abundance and content of serotonin. Besides, prolactin secreted by the pituitary gland was greater in brooding geese than that in laying geese, which was also highly correlated with B. fragilis abundance. This result implied that B. fragilis could promote the secretion of prolactin by the pituitary gland. Together, the current study findings provided the information on gut microbiota influencing broody behavior, B. fragilis produced or driven more serum serotonin, and stimulated the pituitary gland to secret more prolactin, which potentially offered a new enlightenment for the intervention of broody behavior in poultry.

The oral-gut microbiome axis in inflammatory bowel disease: from inside to insight.

Inflammatory bowel disease (IBD) is an idiopathic and persistent inflammatory illness of the bowels, leading to a substantial burden on both society and patients due to its high incidence and recurrence. The pathogenesis of IBD is multifaceted, partly attributed to the imbalance of immune responses toward the gut microbiota. There is a correlation between the severity of the disease and the imbalance in the oral microbiota, which has been discovered in recent research highlighting the role of oral microbes in the development of IBD. In addition, various oral conditions, such as angular cheilitis and periodontitis, are common extraintestinal manifestations (EIMs) of IBD and are associated with the severity of colonic inflammation. However, it is still unclear exactly how the oral microbiota contributes to the pathogenesis of IBD. This review sheds light on the probable causal involvement of oral microbiota in intestinal inflammation by providing an overview of the evidence, developments, and future directions regarding the relationship between oral microbiota and IBD. Changes in the oral microbiota can serve as markers for IBD, aiding in early diagnosis and predicting disease progression. Promising advances in probiotic-mediated oral microbiome modification and antibiotic-targeted eradication of specific oral pathogens hold potential to prevent IBD recurrence.

A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target.

Breast cancer (BC) is the most frequently occurring malignancy and the second cancer-specific cause of mortality in women in developed countries. Over 70% of the total number of BCs are hormone receptor-positive (HR+), and elevated levels of circulating estrogen (E) in the blood have been shown to be a major risk factor for the development of HR+ BC. This is attributable to estrogen's contribution to increased cancer cell proliferation, stimulation of angiogenesis and metastasis, and resistance to therapy. The E metabolism-gut microbiome axis is functional, with subjacent individual variations in the levels of E. It is conceivable that the estrobolome (bacterial genes whose products metabolize E) may contribute to the risk of malignant neoplasms of hormonal origin, including BC, and may serve as a potential biomarker and target. It has been suggested that β-glucuronidase (GUS) enzymes of the intestinal microbiome participate in the strobolome. In addition, it has been proposed that bacterial GUS enzymes from the gastrointestinal tract participate in hormone BC. In this review, we discuss the latest knowledge about the role of the GUS enzyme in the pathogenesis of BC, focusing on (i) the microbiome and E metabolism; (ii) diet, estrobolome, and BC development; (iii) other activities of the bacterial GUS; and (iv) the new molecular targets for BC therapeutic application.

Bacterial Metabolites and Inflammatory Skin Diseases.

The microbiome and gut-skin axis are popular areas of interest in recent years concerning inflammatory skin diseases. While many bacterial species have been associated with commensalism of both the skin and gastrointestinal tract in certain disease states, less is known about specific bacterial metabolites that regulate host pathways and contribute to inflammation. Some of these metabolites include short chain fatty acids, amine, and tryptophan derivatives, and more that when dysregulated, have deleterious effects on cutaneous disease burden. This review aims to summarize the knowledge of wealth surrounding bacterial metabolites of the skin and gut and their role in immune homeostasis in inflammatory skin diseases such as atopic dermatitis, psoriasis, and hidradenitis suppurativa.

The Microbiome-Thyroid Link: A Review of the Role of the Gut Microbiota in Thyroid Function and Disease

The gut microbiota has emerged as a potential regulator of thyroid homeostasis and disease. Recent studies suggest that the composition and diversity of intestinal bacteria can impact thyroid stimulating hormone levels, thyroid hormone synthesis &amp; metabolism and the risk of thyroid conditions like hypothyroidism and autoimmune thyroiditis. However, the mechanisms through which the gut microbiota influences the thyroid remain poorly understood. This review aims to summarize the current evidence on the role of the gut-thyroid microbiome axis in thyroid physiology and pathophysiology. Studies investigating the association of gut dysbiosis with altered thyroid function and disorders like Hashimoto’s thyroiditis were discussed. Potential mechanisms through which gut bacteria may influence thyroid hormone levels and autoimmunity, such as interference with autoantigen presentation, induction of inflammation, and production of metabolites were evaluated. The impact of dietary and probiotic interventions targeting the gut microbiota for managing thyroid disease is assessed. Future research directions focusing on delineating key bacteria influencing thyroid health, characterizing longitudinal microbiota changes in thyroid conditions, and identifying novel microbiota-based therapies are proposed. A deeper understanding of the gut-thyroid axis may lead to microbiota-targeted strategies for managing thyroid disorders.

Cardioprotective properties of quercetin in fescue toxicosis-induced cardiotoxicity via heart-gut axis in lambs (Ovis Aries)

The present study investigated whether quercetin mitigated fescue toxicosis-induced cardiovascular injury via the heart-gut axis. Twenty-four commercial Dorper lambs were stratified by body weight and assigned randomly to diets in one of four groups: endophyte-free without quercetin (E-,Q-), endophyte-positive without quercetin (E+,Q-), endophyte-positive plus 4 g/kg quercetin (E+,Q+) or endophyte-free plus 4 g/kg quercetin (E-,Q+) for 42 days. Body weight and average daily feed intake (ADFI) of lambs fed the endophyte-positive diets showed significant decreases. However, in the groups treated with quercetin, there were significant alterations of cardiac enzymes. Furthermore, reduced fescue toxicosis-induced histopathological lesions of heart and aorta were demonstrated in the E+,Q+ lambs. Results also suggested quercetin eased cardiovascular oxidative injury by inhibiting the increase of oxidative metabolites, and enhancing the levels of antioxidases. Quercetin reduced the inflammation response through suppressing NF-κB signaling pathway activation. Additionally, quercetin ameliorated fescue toxicosis-induced mitochondria dysfunction and improved mitochondrial quality control through enhancing PGC-1α-mediated mitochondrial biogenesis, maintaining the mitochondrial dynamics, and relieving aberrant Parkin/PINK-mediated mitophagy. Quercetin enhanced gastrointestinal microbial alpha and beta diversity, alleviated gut microbiota and microbiome derived metabolites-SCFAs dysbiosis by fescue toxicosis. These findings signified that quercetin may play a cardio-protective role via regulating the heart–gut microbiome axis.