Coccidiosis is a global disease caused by protozoans, typically including Eimeria spp., which pose a significant threat to the normal growth and development of young animals. Coccidiosis affects mainly the gut, where parasite proliferation occurs. The intestinal barrier, which consists of chemical, mechanical, biological, and immune defences, plays a crucial role in protecting the host against pathogens, xenobiotics, and toxins present in the gastrointestinal tract. When animals ingest sporulated Eimeria spp. oocysts, these parasites primarily reproduce in the intestinal tract, causing damage to the structure and function of the intestine. This disruption of intestinal homeostasis adversely affects animal health. Numerous studies have also revealed that Eimeria-infected animals experience slower bone growth rates, inferior meat quality, reduced egg production and quality, as well as impaired growth and development. Therefore, the purpose of this review is to examine the underlying mechanisms through which Eimeria spp. regulate intestinal damage and disturb the balance of the internal environment. Specifically, this review will focus on their effects on the structural basis of the host intestine's chemical, mechanical, biological and immune barriers. This understanding is crucial for the development of effective drugs to prevent the invasion of Eimeria spp. into the intestine, which is of paramount importance for maintaining host health.

Over the past 3 years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

According to the criteria established by the International League Against Epilepsy (ILAE), epilepsy is defined as a disorder characterized by at least two unprovoked seizures occurring more than 24 h apart. Its pathogenesis is closely related to various physiological and pathological factors. Advances in high-throughput metagenomic sequencing have increasingly highlighted the role of gut microbiota dysbiosis in epilepsy. Short-chain fatty acids (SCFAs), the major metabolites of the gut microbiota and key regulators of the gut-brain axis, support physiological homeostasis through multiple mechanisms. Recent studies have indicated that SCFAs not only regulate seizures by maintaining intestinal barrier integrity and modulating intestinal immune responses, but also affect the structure and function of the blood-brain barrier (BBB) and regulate neuroinflammation. This review, based on current literatures, explores the relationship between SCFAs and epilepsy, emphasizing how SCFAs affect epilepsy by modulating the intestinal barrier and BBB. In-depth studies on SCFAs may reveal their therapeutic potential and inform the development of gut microbiota-targeted epilepsy treatments.

Short-chain fatty acids (SCFAs) are a group of organic compounds produced by the fermentation of dietary fibre by the human gut microbiota. They play diverse roles in different physiological processes of the host with implications for human health and disease. This Review provides an overview of the complex microbial metabolism underlying SCFA formation, considering microbial interactions and modulating factors of the gut environment. We explore the multifaceted mechanistic interactions between SCFAs and the host, with a particular focus on the local actions of SCFAs in the gut and their complex interactions with the immune system. We also discuss how these actions influence intestinal and extraintestinal diseases and emerging therapeutic strategies using SCFAs.

Lizhong decoction (LZD), a Traditional Chinese Medicine formula, is widely utilized to treat gastrointestinal diseases, including ulcerative colitis in China for thousands of years.

To investigate whether the protective effect of LZD on ulcerative colitis is dependent on gut microbiota and T-cell immune homeostasis.

The preventive effects of LZD on dextran sodium sulfate (DSS)-induced colitis mice were evaluated through the measurement of body weight, disease activity index, colon length and hematoxylin-eosin staining. Flow cytometry was used to detect the ratio of Th17/Treg cells. Pseudo sterile mice and fecal transplantation experiments were used to investigate whether the preventive effect of LZD was dependent on the gut microbiota. The alterations of gut microbiota were identified by the 16S rDNA sequencing. The content of intestinal short-chain fatty acids (SCFAs) was detected by LC-MS/MS analysis. The downstream signal pathways of SCFAs were detected by the immunoblotting.

LZD administration significantly alleviated weight loss and intestinal injury in DSS-induced colitis mice. LZD administration also promotes the balance of Th17/Treg cells. Moreover, LZD administration relies on gut microbiota to alleviate ulcerative colitis and regulate Th17/Treg cell balance. LZD administration significantly improves gut microbial composition in colitis mice, elevating the abundance of SCFAs producing bacterium such as lachnospiraceae_nk4a136_group and Akkermansia. LZD treatment further increases the abundance of SCFAs and promotes activation of free fatty acid activated receptor 2 (FFAR2).

LZD administration promotes Th17/Treg cell balance in a gut microbiota-SCFAs dependent manner, which in turn ameliorates ulcerative colitis.

To analyze the gut bacterial microbiome in rats with painful diabetic neuropathy (PDN) compared to normal rats.

Type 2 diabetes was induced in rats via a high-fat and high-sugar diet combined with a low dose of streptozotocin. Glucose metabolism and insulin sensitivity were evaluated using intraperitoneal glucose tolerance tests and insulin tolerance tests. The progression of peripheral neuropathy was assessed using the mechanical withdrawal threshold and thermal withdrawal latency. Histopathological analysis of rat colon tissues was performed using hematoxylin-eosin staining to observe morphological changes. The expression levels of pro-inflammatory cytokines TNF-α and IL-1β in spinal cord tissues were measured using enzyme-linked immunosorbent assay (ELISA). Fecal samples were then collected for metagenomic sequencing and analysis.

Behavioral tests revealed reduced mechanical withdrawal threshold and thermal withdrawal latency in PDN rats. Histological analysis showed significant colonic mucosal damage and inflammatory cell infiltration, suggesting impaired intestinal barrier function. Elevated TNF-α and IL-1β levels in spinal cord tissues further highlight peripheral inflammation's role in PDN. Sequencing analysis revealed significant differences in gut microbiota composition between PDN and control rats, with altered Bacillota/Bacteroidota ratios and increased Lactobacillus abundance. Functional annotation analysis, based on the KEGG, EggNOG, and CAZy databases, indicated significant enrichment of metabolic pathways related to carbohydrate and amino acid metabolism, energy metabolism, and cell structure biogenesis in PDN rats. Cluster analysis identified higher functional clustering in Metabolism and Genetic Information Processing pathways in PDN rats.

This study demonstrates that PDN leads to altered gut microbiota composition, disrupted metabolic pathways, and increased inflammation, contributing to the pathological progression of diabetic neuropathy. This study provides new insights into the interplay between gut microbiota and diabetic neuropathy, offering potential avenues for therapeutic interventions targeting microbiome and metabolism.

Neurodevelopmental disorders (NDDs) and epileptic syndromes are complex neurological conditions linked by shared abnormal neurobiological processes. Existing therapies mostly target symptoms, rather than addressing the underlying causes of the disease, leaving a burden of unmet clinical needs.

Emerging evidence suggests a significant role for the gut microbiota and associated immune responses in influencing brain development and function, changing the paradigm of a brain-centric origin of NDDs. This review discusses the pivotal interactions within the gut-immune-brain axis, highlighting how microbial dysbiosis and immune signaling contribute to neurological pathologies. We also explore the potential of microbial management and immunomodulation as novel therapeutic avenues, emphasizing the need for a shift towards addressing the root causes of these disorders rather than just their symptoms.

This integrated perspective offers new insights into the biological underpinnings of NDDs and epilepsy, proposing innovative biomarkers and therapeutic strategies.

Bee pollen, a natural honeybee product, is hailed as a treasure trove of human nutrition. Among the nourishing substances of bee pollen, the constituents with a low molecular weight (such as phenolic acids and flavonoid glycosides) have been extensively studied in the past decades, whereas the polysaccharides with a relatively high molecular weight have received much less attention. To deepen our understanding of bee pollen polysaccharides, this review summarizes the published findings related to their preparation technologies, structural characteristics and biological activities. Among the preparation technologies, ultrasonic-assisted extraction is currently the most effective technology for the recovery of polysaccharides from bee pollen, because ultrasound can crack the pollen exine into fragments and facilitate the release of polysaccharides present in the pollen intine. The preliminary structures, including the molecular weight and monosaccharide composition, of bee pollen polysaccharides have been widely reported, but their fine structures have not fully elucidated. Moreover, bee pollen polysaccharides have antioxidant, immunomodulatory, and antitumor activities, exhibiting potential application in functional foods. Furthermore, bee pollen polysaccharides can modulate the composition of gut microbiota and promote the production of short-chain fatty acids. It is expected that this review can provide inspiration for the development and utilization of bee pollen polysaccharides.

Chimeric antigen receptor (CAR) T-cell therapy represents a promising approach for cancer treatment, with receptor tyrosine kinase-like orphan receptor 1 (ROR1) emerging as a novel target in malignancies. This study investigates how short-chain fatty acids (SCFAs), key microbiota-derived metabolites, modulate anti-ROR1 CAR T-cell efficacy using a physiologically relevant intestinal adenocarcinoma-on-chip model that replicates the human intestinal microenvironment. The findings demonstrate that propionate and butyrate inhibit anti-ROR1 CAR T-cell function by reducing infiltration, cytotoxicity, and cytokine release while preserving junctional integrity within the tumor model. Mechanistically, these SCFAs inhibit histone deacetylase activity and promote a phenotype switch toward regulatory T-cells, as indicated by increased expression of FoxP3 and RORγt. Additionally, propionate and butyrate upregulate PD-1 and TIM-3, markers of T-cell exhaustion and immune tolerance, and induce a dose- and time-dependent reduction in proinflammatory cytokines. In contrast, acetate and pentanoate promote a proinflammatory T helper 17 phenotype. These results highlight the immunomodulatory effects of SCFAs on CAR T-cell function, emphasizing the need to consider microbiota-derived metabolites in CAR T-cell therapies.

Infancy is a vulnerable and critical phase in the acquisition of the gut microbiome and the establishment of immune function. Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are compounds mostly produced by the microbiome through various metabolic pathways and play an indispensable role in connecting the microbiome and the adaptive immune system. This review aims to summarise recent findings regarding the intricate relationship between SCFAs, the gut microbiome, and T lymphocytes with a focus on early life interactions. The paper discusses factors affecting the establishment of the neonatal microbiome, especially human milk versus formula milk, and how these influence SCFA concentrations in feces, which in turn directly impact T cell development and function. Despite recent advances in understanding the role of gut microbiome derived SCFAs in adults, a significant knowledge gap remains in translating these findings to neonates and exploring the utility of SCFAs as a potential therapeutic intervention in inflammatory complications of preterm and term neonates. IMPACT: This review highlights potential therapeutic applications of short-chain fatty acids (SCFAs) in neonatal care, particularly in preventing and treating inflammatory conditions. This could lead to new treatment strategies for conditions like NEC and other immune-mediated disorders in neonates. By identifying significant knowledge gaps in neonatal SCFA research, this review helps future investigations toward understanding SCFA mechanisms specifically in neonates, potentially leading to age-appropriate therapeutic interventions. Understanding the relationship between early-life factors (such as feeding methods and microbiome development) and immune system development through SCFAs could inform public health policies and recommendations for infant nutrition and care practices.

Alzheimer's disease (AD), a prevalent neurodegenerative disorder, represents a significant global health challenge, characterized by cognitive decline and neuroinflammation. Recent investigations have highlighted the critical role of the gut-brain axis in the pathogenesis of AD, particularly focusing on the influence of short-chain fatty acids (SCFAs), metabolites produced by the gut microbiota through the fermentation of dietary fiber. Among SCFAs, butyrate has emerged as a crucial mediator, positively impacting various pathological processes associated with AD, including epigenetic regulation, neuroinflammation modulation, maintenance of the blood-brain barrier (BBB), enhanced intestinal integrity, regulation of brain metabolism, and interference with amyloid protein formation as well as tau protein hyperphosphorylation. Furthermore, distinctions in butyrate profile and microbial communities have been observed between AD patients and healthy individuals, underscoring the importance of gut microbiota in AD progression. This review summarizes the current understanding of the many functions of butyrate in reducing the consequences of AD and emphasizes the possibility of addressing the gut microbiota as a therapeutic approach to managing AD.

Fatty acids (FAs) have various functions on cell regulation considering their abundant types and metabolic pathways. In addition, the relation between FA and other nutritional metabolism makes their functions more complex. As the first place for diet-derived FA metabolism, intestine is significantly influenced despite lack of clear conclusions due to the inconsistent findings. In this review, we discuss the regulation of fatty acid metabolism on the fate of intestinal stem cells in homeostasis and disorders, and also focus on the intestinal tumor development and treatment from the aspect of gut microbiota-epithelium-immune interaction. We summarize that the balances between FA oxidation and glycolysis, between oxidative phosphorylation and ketogenesis, between catabolism and anabolism, and the specific roles of individual FA types determine the diverse effects of intestinal FA metabolism in different cases. We hope this will inspire further dissection and suggest precise dietary/metabolic intervention for different demands related to intestinal health.

Malignant tumors are heterogeneous diseases characterized by uncontrolled cell proliferation, invasion, metastasis, and/or recurrence of their malignancies. In particular, cancer stem cells (CSCs) within these tumors might be responsible for the property of invasiveness and/or therapies-resistance. CSCs are a self-renewing, awfully tumorigenic subpopulation of cancer cells, which are notorious for strong chemoresistance and are frequently responsible the aggravated invasion, metastasis, and/or recurrence. Developing targeting therapies against CSCs, therefore, may be deliberated a more encouraging mission for the greater cancer therapy. Innovation for a more potent anti-CSC treatment has been required as soon as possible. Interestingly, vitamin D could modulate the inflammatory condition of the tumor microenvironment (TME) by successfully affecting CSCs, which has an imperative role in determining the malignant phenotype of CSCs. In addition, vitamin D may also contribute to the regulation of the malignant behaviors of CSCs. Consistently, vitamin D could have potential applications for the significant inhibition of several tumor growths within various cancer therapies. The biological significance of vitamin D for CSCs regulation may be involved in the function of APRO family proteins. Therefore, vitamin D could be one of the innovative therapeutic modalities for the development of novel CSCs related tumor therapies.

In the present study, an inulin-type fructan (ITF) with the degree polymerization (DP) of 21 was isolated from Codonopsis pilosula roots and its structure was characterized by FT-IR, MALDI-TOF-MS and NMR. The immunomodulatory and intestinal protective effects of ITF were investigated on immunosuppressive mice. Male BALB/c mice were pretreated with cyclophosphamide (Cy) for 3 days to establish an immunosuppressive model followed by ITF treatment. The results demonstrated that compared with the model group, ITF administration significantly increased immune organ index (P<0.05), alleviated intestinal villus damage, stimulated serum cytokine secretion including Ig G, IL-4, IL-6, IL-2, TNF-α, and INF-γ (P<0.05), upregulated the expression of Occludin and Claudin-1 (P<0.05), and increased CD4+ and CD8+ T cells of ileum in Cy-induced mice (P<0.05). Furthermore, ITF restored the intestinal microbiota dysbiosis caused by Cy by increasing the abundance of Muribaculaceae, Blautia, Odoribacter, Lactobacillus and decreasing the abundance of Lachnospiraceae_NK4A136_group (P<0.05). Meanwhile, ITF increased the production of short-chain fatty acids (SCFAs) including acetic acid, propionic acid and butyric acid (P<0.05). These results indicated that ITF can ameliorate cyclophosphamide-induced immunosuppression and intestinal barrier injury, and restore gut microbiota dysbiosis. This study provided important evidences for the immunomodulatory and intestinal protective effects of the ITF from C. pilosula.

The gut microbiome plays a pivotal role in modulating cancer therapies, including immunotherapy and chemotherapy. Emerging evidence demonstrates its influence on treatment efficacy, immune response, and resistance mechanisms. Specific microbial taxa enhance immune checkpoint inhibitor efficacy, while dysbiosis can contribute to adverse outcomes. Chemotherapy effectiveness is also influenced by microbiome composition, with engineered probiotics and prebiotics offering promising strategies to enhance drug delivery and reduce toxicity. Moreover, microbial metabolites, such as short-chain fatty acids, and engineered microbial systems have shown potential to improve therapeutic responses. These findings underscore the importance of personalized microbiome-based approaches in optimizing cancer treatments.

Neurodegenerative diseases (NDDs) such as Alzheimer's and Parkinson's disease are increasing globally and represent a significant cause of age-related death in the population. Recent studies emphasize the strong association between environmental stressors, particularly dietary factors, and brain health and neurodegeneration unsatisfactory outcomes. Despite ongoing efforts, the efficiency of current treatments for NDDs remains wanting. Considering this, nootropic foods with neuroprotective effects are of high interest as part of a possible long-term therapeutic strategy to improve brain health and alleviate NDDs. However, since it is a new and emerging area in food and neuroscience, there is limited information on mechanisms and challenges to consider for this to be a successful intervention. Here, we seek to address these gaps by presenting a comprehensive review of possible pathways or mechanisms including mutual interactions governing nootropic food metabolism, linkages of the pathways with NDDs, intake, and neuroprotective properties of nootropic foods. We also discuss in-depth intervention with nootropic compounds and dietary patterns in NDDs, providing a detailed exploration of their mechanisms of action. Additionally, we analyze the demand, challenges, and future directions for successful development of nootropic foods targeting NDDs.

Inflammatory bowel disease (IBD), a chronic inflammatory disorder of the gastrointestinal tract, is frequently complicated by extraintestinal manifestations such as functional hyposplenism. Increasing evidence highlights its pathogenesis as a multifactorial interplay of gut dysbiosis, intestinal barrier dysfunction, and dysregulated immune responses. While probiotics, particularly Lactobacillus spp., have emerged as potential therapeutics for IBD, restoring intestinal homeostasis, their systemic immunomodulatory effects remain underexplored. Here, we investigated the protective role of Lactobacillus johnsonii N5 in DSS-induced colitis, focusing on inflammation inhibition and splenic T cell regulation. Pretreatment with L. johnsonii N5 significantly attenuated colitis severity, as evidenced by preserved body weight, reduced disease activity index, and prevention of colon shortening. N5 suppressed colonic pro-inflammatory factors such as TNF-α, Il-1b, Il-6, and CXCL1, while elevating anti-inflammatory IL-10 at both mRNA and protein levels. Transcriptomic analysis of the spleen revealed that N5 mediated the downregulation of inflammatory pathways, including the IL-17 and TNF signaling pathways, as well as the HIF-1 signaling pathway, and modulated the metabolic pathway of oxidative phosphorylation. Flow cytometry analysis demonstrated that N5 rebalanced splenic Treg/Th17 responses by expanding the Treg population and reducing the production of IL-17A in Th17 cells. Notably, Th17-associated IL-17A positively correlated with intestinal pro-inflammatory mediators, emphasizing the role of Th17 cells in driving colitis. In contrast, splenic Treg abundance positively correlated with colonic IL-10 levels, suggesting a link between systemic immune regulation and intestinal anti-inflammatory responses. Our study underscores the therapeutic potential of targeting gut-immune crosstalk through probiotics, thereby offering valuable insights for developing live bacterial-based interventions for IBD and other inflammatory disorders.

The immune system has long been recognized as a key driver in the progression of heart failure (HF). However, clinical trials targeting immune effectors have consistently failed to improve patient outcome across different HF aetiologies. The activation of the immune system in HF is complex, involving a broad network of pro-inflammatory and immune-modulating components, which complicates the identification of specific immune pathways suitable for therapeutic targeting. Increasing attention has been devoted to identifying gut microbial pathways that affect cardiac remodelling and metabolism and, thereby impacting the development of HF. In particular, gut microbiota-derived metabolites, absorbed by the host and transported to the peripheral circulation, can act as signalling molecules, influencing metabolism and immune homeostasis. Recent reports suggest that the gut microbiota plays a crucial role in modulating immune processes involved in HF. Here, we summarize recent advances in understanding the contributory role of gut microbiota in (auto-)immune pathways that critically determine the progression or alleviation of HF. We also thoroughly discuss potential gut microbiota-based intervention strategies to treat or decelerate HF progression.

Inflammatory bowel disease (IBD) is an idiopathic gastrointestinal disease with drastically increasing incidence rates. Due to its multifactorial etiology, a precise investigation of the pathogenesis is extremely difficult. Although reductionist cell culture models and more complex disease models in animals have clarified the understanding of individual disease mechanisms and contributing factors of IBD in the past, it remains challenging to bridge research and clinical practice. Conventional 2D cell culture models cannot replicate complex host-microbiota interactions and stable long-term microbial culture. Further, extrapolating data from animal models to patients remains challenging due to genetic and environmental diversity leading to differences in immune responses. Human intestine organ-on-chip (OoC) models have emerged as an alternative in vitro model approach to investigate IBD. OoC models not only recapitulate the human intestinal microenvironment more accurately than 2D cultures yet may also be advantageous for the identification of important disease-driving factors and pharmacological interventions targets due to the possibility of emulating different complexities. The predispositions and biological hallmarks of IBD focusing on host-microbiota interactions at the intestinal mucosal barrier are elucidated here. Additionally, the potential of OoCs to explore microbiota-related therapies and personalized medicine for IBD treatment is discussed.

In solid tumors, the tumor microenvironment (TME) is a complex mix of tumor, immune, stromal cells, fibroblasts, and the extracellular matrix. Cytotoxic T lymphocytes (CTLs) constitute a fraction of immune cells that may infiltrate into the TME. The primary function of these T-cells is to detect and eliminate tumor cells. However, due to the immunosuppressive factors present in the TME primarily mediated by Myeloid-Derived Suppressor Cells (MDSCs), Tumor associated macrophages (TAMs), Cancer Associated Fibroblasts (CAFs) as well as the tumor cells themselves, T-cells fail to differentiate into effector cells or become dysfunctional and are unable to eliminate the tumor. In addition, chronic antigen stimulation within the TME also leads to a phenomenon, first identified in chronic lymphocytic choriomeningitis virus (LCMV) infection in mice, where the T-cells become exhausted and lose their effector functions. Exhausted T-cells (Tex) are characterized by the presence of remarkably conserved inhibitory receptors, transcription and signaling factors and the downregulation of key effector molecules. Tex cells have been identified in various malignancies, including melanoma, colorectal and hepatocellular cancers. Recent studies have indicated novel strategies to reverse T-cell exhaustion. These include checkpoint inhibitor blockade targeting programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), or combinations of different immune checkpoint therapies (ICTs) or combination of ICTs with cytokine co-stimulation. In this review, we discuss aspects of T-cell dysfunction within the TME with a focus on T-cell exhaustion. We believe that gaining insight into the mechanisms of T-cell exhaustion within the TME of human solid tumors will pave the way for developing therapeutic strategies to target and potentially re-invigorate exhausted T-cells in cancer.

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and emotional instability, primarily resulting from the abnormal accumulation of mutant huntingtin protein. Growing research highlights the role of intestinal microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), in modulating HD progression. SCFAs, including acetate, propionate, and butyrate, are produced by gut bacteria through dietary fiber fermentation and are recognized for their neuroprotective properties. Evidence suggests that SCFAs regulate neuroinflammation, neuronal communication, and metabolic functions within the central nervous system (CNS). In HD, these compounds may support neuronal health, reduce oxidative stress, and enhance blood-brain barrier (BBB) integrity. Their mechanisms of action involve binding to G-protein-coupled receptors (GPCRs) and modulating gene expression through epigenetic pathways, underscoring their therapeutic potential. This analysis examines the significance of SCFAs in HD, emphasizing the gut-brain axis and the benefits of dietary interventions aimed at modifying gut microbiota composition and promoting SCFA production. Further research into these pathways may pave the way for novel HD management strategies and improved therapeutic outcomes.

Interactions between metastatic cancer cells and the brain microenvironment regulate brain metastasis (BrMet) progression. Central nervous system (CNS)-native and peripheral immune cells influence the BrMet immune landscape, but the dynamics and factors modulating this microenvironment remain unclear. As the gut microbiome impacts CNS and peripheral immune activity, we investigated its role in regulating immune response dynamics throughout BrMet stages. Antibiotic-induced (ABX) gut dysbiosis significantly increased BrMet burden versus controls but was equalized with fecal matter transplantation, highlighting microbiome diversity as a regulator of BrMet. Single-cell sequencing revealed a highly dynamic immune landscape during BrMet progression in both conditions. However, the timing of the monocyte inflammatory response was altered. Microglia displayed an elevated activation signature in late-stage metastasis in ABX-treated mice. T cell and microglia perturbation revealed involvement of these cell types in modulating BrMet under gut dysbiosis. These data indicate profound effects on immune response dynamics imposed by gut dysbiosis across BrMet progression.

Here, we report significant changes in the composition of the lung microbiome and metabolome of mice under immune suppression, infection of immunosuppressed mice with virulent and avirulent strains of the clinically important human-pathogenic fungus Aspergillus fumigatus, and treatment with the clinically used antifungal drug voriconazole. Our data also indicate the important role of the gut microbiome for lung homeostasis mediated by the plasma metabolome. In the lung microbiome, DNA sequencing indicates that infection by A. fumigatus leads to a significant increase of anaerobic bacteria, most prominently of Ligilactobacillus murinus; the latter has been confirmed by qPCR analyses. We also isolated live bacteria, including L. murinus, from the murine lower respiratory tract. Co-cultivation of L. murinus and A. fumigatus leads to a reduction in oxygen concentration accompanied by an increase of L. murinus cells, suggesting that A. fumigatus establishes a microaerophilic niche, thereby promoting growth of anaerobic bacteria.

Several pathologies with metabolic origin, such as hyperuricemia and gout, have been associated with the gut microbiota taxonomic profile. However, there is no evidence of which bacterial genes are being expressed in the gut microbiome, and of their potential effects on hyperuricemia and gout. We sequenced the RNA of 26 fecal samples from 10 healthy normouricemic controls, 10 with asymptomatic hyperuricemia (AH), and six gout patients. The coding sequences were mapped to KEGG orthologues (KO). We compared the expression levels using generalized linear models and validated the expression of four KO in a larger sample by qRT-PCR. A distinct genetic expression pattern was identified among groups. AH individuals and gout patients showed an over-expression of KOs mainly related to pyruvate metabolism (Log2foldchange > 23, p-adj ≤ 3.56 × 10- 9), the pentose pathway (Log2foldchange > 24, p-adj < 1.10 × 10-12) and purine metabolism (Log2foldchange > 22, p-adj < 1.25 × 10- 7). AH subjects had lower expression of KO related to glycine metabolism (Log2foldchange=-18, p-adj < 1.72 × 10-6) than controls. Gout patients had lower expression (Log2foldchange=-22.42, p-adj < 3.31 × 10- 16) of a KO involved in phenylalanine biosynthesis, in comparison to controls and AH subjects. The over-expression seen for the KO related to pyruvate metabolism and the pentose pathway in gout patients´ microbiome was validated. There is a differential gene expression pattern in the gut microbiome of normouricemic individuals, AH subjects and gout patients. These differences are mainly located in metabolic pathways involved in acetate precursors and bioavailability of amino acids.

Gut microbiota imbalance is well-known as one important trigger of allergic asthma. Ma-Xing-Shi-Gan decoction (MXSG) is a traditional Chinese medicine prescription with ideal clinical efficacy on asthma. However, whether and how MXSG exerts its efficacy on asthma through gut microbiota remains unclear.

To investigate the underlying mechanism of MXSG against asthma using multi-omics technologies.

An asthma model was established using 8-week-old C57BL/6 J mice, after which they were daily administrated with high-, medium- and low-dose MXSG for 7 days. Histopathological examinations and flow cytometry were performed to evaluate the effects of MXSG on lung immune injury. Key regulatory pathways were predicted via network pharmacology and verified using 16S rRNA sequencing, metagenomics, metabolomics, and in vivo experiments including the knockout of the targeting gene.

MXSG alleviated asthma symptoms, elevated intestinal microbial diversities, and enriched potential beneficial microbes such as Lactococcus, Lactobacillus, and Limosilactobacillus. Network pharmacology and experimental validation highlighted the IL-17/Treg signaling as crucial for asthma treatment. IL-17 knockout experiments revealed its necessity for Treg differentiation during asthma. Moreover, IL-17-deficient asthmatic mice exhibited lower levels of Lactobacillus and significant changes in microbial genes involving histone deacetylases (HDAC) and short-chain fatty acids (SCFAs). Finally, MXSG significantly boosted SCFA production and reduced HDAC9 expression, which were correlated with Treg cell ratios.

Our study delineates a novel mechanism where MXSG synergizes with the IL-17 family to enrich intestinal beneficial microbes (e.g. Lactobacillus) and SCFAs. This inhibits the expression of SCFA-downstream HDAC9 to promote Treg differentiation, and thus potentially alleviates asthma.

The composition and functionality of the gut microbiota (GM) changes throughout the life course. As we move into older age, it starts to shift towards a less healthy one, which may lead to an imbalance in the GM community. Strategies that can reverse age-related dysbiosis are an important part of healthy aging. Little is known about the GM composition of older adults with different physical activity (PA) levels and whether it might contribute to healthy ageing. The aim of this study was to compare the GM composition of older adults with different PA levels and assess if it is associated with healthy ageing. 101 participants aged between 65-85 years undertook anthropometric measures, a 6-min walking test, wore an accelerometer for 7 days and provided a faecal sample. Faecal GM composition was analysed using 16S rRNA sequencing. We found that those who fulfilled the WHO/UK PA recommendations had higher relative abundance of several health-related bacteria such as Lactobacillus, F. prausnitzii and Roseburia intestinalis and lower abundance of disease-associated bacteria such as D.piger or Enterobacterales when compared to those who did not reach PA recommendations. These findings suggest that PA might improve the GM composition and has the potential to, at least partially, revert age-associated dysbiosis and promote healthy ageing.

Anti-tumor immunity, including innate and adaptive immunity is critical in inhibiting tumorigenesis and development of tumor. The adaptive immunity needs specific lymph organs such as tertiary lymphoid structures (TLSs), which are highly correlated with improved survival outcomes in many cancers. In recent years, with increasing attention on the TLS in tumor microenvironment, TLSs have emerged as a novel target for anti-tumor therapy. Excitingly, studies have shown the contribution of TLSs to the adaptive immune responses. However, it is unclear how TLSs to form and how to more effectively defense against tumor through TLS formation. Recent studies have shown that the inflammation plays a critical role in TLS formation. Interestingly, studies have also found that gut microbiota can regulate the occurrence and development of inflammation. Therefore, we here summarize the potential effects of gut microbiota- mediated inflammation or immunosuppression on the TLS formation in tumor environments. Meanwhile, this review also explores how to manipulate mature TLS formation through regulating gut microbiota/metabolites or gut microbiota associated signal pathways for anti-tumor immunity, which potentially lead to a next-generation cancer immunotherapy.

Inflammatory Bowel Disease (IBD) is an autoimmune disease characterized by chronic relapsing inflammation of the intestinal tract. Gut microbiota (GM) and CD4+T cells are important in the development of IBD. A lot of studies have shown that GM and their metabolites like short-chain fatty acids, bile acids and tryptophan can be involved in the differentiation of CD4+T cells through various mechanisms, which in turn regulate the immune homeostasis of the IBD patients. Therefore, regulating CD4+T cells through GM may be a potential therapeutic direction for the treatment of IBD. Many studies have shown that Traditional Chinese Medicine (TCM) formulas and some herbal extracts can affect CD4+T cell differentiation by regulating GM and its metabolites. In this review, we mainly focus on the role of GM and their metabolites in regulating the differentiation of CD4+T cells and their correlation with IBD. We also summarize the current research progress on the regulation of this process by TCM.

Electroacupuncture (EA) has been shown to ameliorate brain injury and protect against intestinal injury after ischemic stroke. These protective effects are closely associated with the enhancement of regulatory T (Treg) cell numbers and function in the intestine, as well as the inhibition of intestinal γδ T cell production and their migration to the brain. This study aimed to elucidate the potential mechanism by which EA regulates intestinal Treg cell differentiation after stroke. Sprague-Dawley rats were divided into three groups: the sham group, the middle cerebral artery occlusion (MCAO) group, and the MCAO plus EA (MEA) group. The MCAO model was generated by occluding the middle cerebral artery. EA was applied to Baihui (GV20) acupoint once daily. Samples were collected 3 days after reperfusion. Our results showed that EA reduced the inflammatory response in the brain and intestine after ischemic stroke. EA treatment increased the percentage of Treg cells in the small intestine of rats. EA increased the levels of SCFAs, while also inhibiting histone deacetylase activity (HDAC). Additionally, acetylated Foxp3 protein in the small intestine was increased after EA treatment. These results suggest that EA at GV20 alleviates brain and intestinal inflammatory injury in stroke rats, potentially through the enhancement of SCFA-mediated Foxp3 acetylation in Treg cells.

Food allergies are increasing globally, particularly in Asia; however, the etiologies of allergic diseases remain poorly understood despite comprehensive studies conducted across a variety of populations. Epidemiological research demonstrates that food allergy is more prevalent in Westernized or urbanized societies than in rural or developing ones. As such, comparing the distribution and patterns of food allergies as well as the environmental exposures between regions may provide insight into potential causal and protective factors of food allergy. Diet is an important exposome that has been shown to modulate the immune system both directly and indirectly via pathways involving the microbiota. Changes in dietary patterns, especially the shift to a Westernized diet with reduced dietary fiber and an abundance of processed foods, impact the gut and skin epithelial barrier and contribute to the development of chronic inflammatory diseases, such as food allergy. Although dietary intervention is believed to have tremendous potential as a strategy to promote immunological health, it is essential to recognize that diet is only one of many factors that have changed in urbanized societies. Other factors, such as pollution, microplastics, the use of medications like antibiotics, and exposure to biodiversity and animals, may also play significant roles, and further research is needed to determine which exposures are most critical for the development of food allergies.

Evidence is accumulating that short-chain fatty acids (SCFAs) produced by the gut microbiota play pivotal roles in host metabolism. They contribute to the metabolic regulation and energy homeostasis of the host not only by preserving intestinal health and serving as energy substrates but also by entering the systemic circulation as signaling molecules, affecting the gut-brain axis and neuroendocrine-immune network. This review critically summarizes the current knowledge regarding the effects of SCFAs in the fine-tuning of the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, with an emphasis on the complex relationships among diet, microbiota-derived metabolites, T2DM inflammation, glucose metabolism, and the underlying mechanisms involved. We hold an optimistic view that elucidating how diet can influence gut bacterial composition and activity, SCFA production, and metabolic functions in the host will advance our understanding of the mutual interactions of the intestinal microbiota with other metabolically active organs, and may pave the way for harnessing these pathways to develop novel personalized therapeutics for glucometabolic disorders.

Childhood is a multifactorial disease, and recent research highlights the influence of early-life microbial communities in shaping disease risk. This review explores the roles of the gut and respiratory microbiota in asthma development, emphasizing the importance of early microbial exposure. The gut microbiota has been particularly well studied, with certain taxa like Faecalibacterium and Bifidobacterium linked to asthma protection, whereas short-chain fatty acids produced by gut microbes support immune tolerance through the gut-lung axis. In contrast, the respiratory microbiota, though low in biomass, shows consistent associations between early bacterial colonization by Streptococcus, Moraxella, and Haemophilus and increased asthma risk. The review also addresses the emerging roles of the skin microbiota and environmental fungi in asthma, though findings remain inconsistent. Timing is a critical factor, with early-life disruptions, such as antibiotic use, potentially leading to increased asthma risk. Despite significant advances, there are still unresolved questions about the long-term consequences of early microbial perturbations, particularly regarding whether microbial dysbiosis is a cause or consequence of asthma. This review integrates current findings, highlighting the need for deeper investigation into cross-organ interactions and early microbial exposures to understand childhood asthma pathophysiology.

Antibiotic (ABX)-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies. In this study, we observed that prior exposure to broad-spectrum ABXs with extended anaerobic coverage such as piperacillin-tazobactam and meropenem was associated with worse anti-CD19 CAR-T therapy survival outcomes in patients with large B-cell lymphoma (N = 422) than other ABX classes. In a discovery subset of these patients (n = 67), we found that the use of these ABXs was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n = 58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery, n = 40; validation, n = 28). These findings were recapitulated in an immune-competent CAR-T mouse model, in which meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-Ts, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy. This trial was registered at www.clinicaltrials.gov as #NCT06218602.

Inflammatory bowel disease is characterized by severe imbalance of intestinal flora and metabolic disorders. Recent studies have demonstrated that probiotics can effectively alleviate inflammatory bowel disease by restoring the intestinal flora structure and modulating the immune response. However, the role of probiotics in regulating intestinal metabolism disorders is still unclear. This study explores the role of probiotic B. cereus in alleviating DSS-induced colitis. The findings indicated probiotic B. cereus treatment mitigated tissue damage and apoptosis during inflammation. Metabolome and transcriptome analysis revealed B. cereus activated the cholic acid-FXR axis by increasing cholic acid levels, which promoted the gene expression level of NF-κB inhibitor α, reduced the IL-1β, IL-6, IL-18 and TNF-α concentrations. Furthermore, it effectively mitigated the DSS-induced disruption of bile acid metabolism, arginine metabolism, and linoleic acid metabolism. This study explores the effect and mechanisms of probiotic B. cereus on alleviating DSS-induced colitis. It aims to provide a theoretical basis for microbial therapy in inflammatory bowel disease. SIGNIFICANCE: This study used metabolome and transcriptome to reveal the roles and mechanisms, which probiotic Bacillus cereus modulates metabolic disorders and alleviate DSS-induced colitis. We identified the cholic acid-FXR axis as an important target for alleviating DSS-induced colitis. These findings provide new insights into microbial treatment strategies for IBD.

The short-chain fatty acid (SCFA) propionate, beyond its actions on the intestine, has been able to lower inflammation and modulate angiogenesis and fibrogenesis in pathological conditions in experimental animal models. Its effects on foreign body reaction (FBR), an abnormal healing process induced by implantation of medical devices, have not been investigated. We have evaluated the effects of sodium propionate (SP) on inflammation, neovascularization and remodeling on a murine model of implant-induced FBR. Polyether-polyurethane sponge discs implanted subcutaneously in C57BL/6 mice provided the scaffold for the formation of the fibrovascular tissue. Fifteen-day old implants of the treated group (SP, 100 mg/kg for 14 days) presented a decrease in the inflammatory response as evaluated by cellular influx (flow cytometry; Neutrophils 54%; Lymphocytes 25%, Macrophages 40%). Myeloperoxidase activity, TNF-α levels and mast cell number were also lower in the treated group relative to the control group. Angiogenesis was evaluated by blood vessel number and VEGF levels, which were downregulated by the treatment. Moreover, the number of foreign body giant cells HE (FBGC) and the thickness of the collagenous capsule were reduced by 58% and 34%, respectively. Collagen deposition inside the implant, TGF-β1 levels, α-SMA and TGF-β1 expression were also reduced. These effects may indicate that SP holds potential as a therapeutic agent for attenuating adverse remodeling processes associated with implantable devices, expanding its applications in biomedical contexts.