Short-chain fatty acids (SCFAs), produced by dietary fiber fermentation in the colon, play essential roles in cellular metabolism, with butyrate notably modulating immune responses and epigenetic regulation. Their production contributes to an acidic colonic environment where protonated SCFAs permeate membranes, leading to intracellular acidification and SCFA accumulation. Using our method to measure intracellular pH, we investigated how extracellular pH influences butyrate-induced acidification and immunomodulatory effects in human macrophages. Our data show that butyrate accumulates and acidifies cells at acidic extracellular pH due to the permeability of its protonated form. While inflammatory cytokine production was mildly influenced by extracellular pH, butyrate-induced histone acetylation exhibited a pH dependence, underscoring the importance of considering extracellular pH when assessing the SCFA's functions.

Liver transplantation (LT) is the ultimate treatment for patients with end-stage liver disease or early hepatocellular carcinoma. In the context of LT, because of the unique immunological characteristics of human liver allograft, 5%-20% of selected LT recipients can achieve operational tolerance. Nonetheless, there remains a risk of rejection in LT patients. Maintaining immune homeostasis is thus crucial for improving clinical outcomes in these patients. In mechanism, several immune cells, including dendritic cells, Kupffer cells, myeloid-derived suppressor cells, hepatic stellate cells, regulatory B cells, and CD4 + regulatory T cells (Treg), contribute to achieving tolerance following LT. In terms of Treg, it plays a role in successfully minimizing immunosuppression or achieving tolerance post-LT while also reducing the risk of rejection. Furthermore, the gut microbiome modulates systemic immune functions along the gut-liver axis. Recent studies have explored changes in the microbiome and its metabolites under various conditions, including post-LT, acute rejection, and tolerance. Certain functional microbiomes and metabolites exhibit immunomodulatory functions, such as the augmentation of Treg, influencing immune homeostasis. Therefore, understanding the mechanisms of tolerance in LT, the role of Treg in tolerance and rejection, as well as their interactions with gut microbiome, is vital for the management of LT patients.

The gut microbial importance and its crucial roles in host digestion, immunity, and metabolism have received widely attention. Horses, especially indigenous varieties such as Mongolian horses (MGH) and Guizhou horses (GZH), have not received sufficient attention, and the characteristics of their gut microbiota are still unclear. For this purpose, we collected faecal samples from eight MGH and eight GZH to compare their gut microbial differences using amplicon sequencing. The results of alpha diversity analysis indicated that the gut bacterial diversity and gut fungal abundance in GZH were significantly higher than those in MGH. Meanwhile, beta diversity revealed that there were significant differences in the gut bacterial and fungal structures between GZH and MGH. Although the dominant bacterial and fungal phyla of GZH and MGH were the same, there were a large number of significantly different bacteria and fungi between both groups. Moreover, we observed that there were 32 phyla (23 bacterial phyla and 9 fungal phyla) and 718 genera (383 bacterial genera and 335 fungal genera) with significant differences between the GZH and MGH. Notably, this study also revealed some differences in intestinal functions between MGH and GZH, such as chemoheterotrophy, fermentation, and cellulolysis. To our knowledge, this is the first report on the comparative analysis of the gut microbiota between MGH and GZH. Our results demonstrated that GZH have a richer and more diverse gut microbiota compared with MGH. Additionally, these results are important for understanding the gut microbial characteristics of indigenous horse.

The intestinal epithelium represents a critical interface between the host and external environment, serving as the second largest surface area in the human body after the lungs. This dynamic barrier is sustained by specialized epithelial cell types and their complex interactions with the gut microbiota. This review comprehensively examines the recent advances in understanding the bidirectional communication between intestinal epithelial cells and the microbiome. We briefly highlight the role of various intestinal epithelial cell types, such as Paneth cells, goblet cells, and enteroendocrine cells, in maintaining intestinal homeostasis and barrier function. Gut microbiota-derived metabolites, particularly short-chain fatty acids and bile acids, influence epithelial cell function and intestinal barrier integrity. Additionally, we highlight emerging evidence of the sophisticated cooperation between different epithelial cell types, with special emphasis on the interaction between tuft cells and Paneth cells in maintaining microbial balance. Understanding these complex interactions has important implications for developing targeted therapeutic strategies for various gastrointestinal disorders, including inflammatory bowel disease, metabolic disorders, and colorectal cancer.

Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.

This study investigates the role of Gum Arabic Mannose Oligosaccharides (GA-MOS) in modulating gut microbiota and alleviating symptoms of Inflammatory Bowel Disease (IBD). Employing both in vitro and in vivo models, we explored how GA-MOS influences microbial communities, particularly focusing on their capacity to enhance health-associated bacteria and reduce pathogenic species within the gut environment. Our findings reveal that GA-MOS treatment significantly altered the gut microbiota composition, increasing the abundance of anti-inflammatory bacteria while decreasing pro-inflammatory species, thus contributing to a reduction in gut inflammation and an improvement in intestinal barrier function. Detailed molecular analyses further demonstrated that these changes in microbiota were associated with modifications in the host's immune response, particularly through the suppression of key inflammatory pathways and cytokines involved in IBD progression. These results underscore the potential of dietary polysaccharides like GA-MOS as therapeutic agents in managing dysbiosis and inflammatory conditions in the gut, offering a promising approach for enhancing microbial health and overall disease management in IBD. This study provides novel insights into the bioactive properties of MOS and their interactions with gut microbiota, suggesting broader implications for their use in microbiome-centered therapies.

Intestinal disease is becoming increasingly prevalent in poultry production; however, the effect of BEC in laying hens challenged with C. perfringens and coccidia is limited. This study aimed to investigate the effects of dietary supplementation with BEC on intestinal and ovarian health in laying hens challenged with C. perfringens and coccidia. A total of 80 Lohmann gray hens (35 weeks) were randomly assigned to two dietary groups supplemented with BEC (0 or 1000 mg/kg). Each group contained 40 replicates, with one bird each (one hen per cage). During the sixth week of the trial, half of the laying hens in each group (n = 20) were administered 40 mL C. perfringens (2.5 × 1010 CFU/mL) and 0.15 mL coccidia (55,000 sporangia/mL), while the other half (n = 20) were administered 40 mL phosphate-buffered saline (PBS). The results indicated that those challenged with C. perfringens and coccidia had severely damaged jejunal and ovarian histopathological morphology, increased oxidative damage, decreased cecal acetic acid and butyric acid content (p < 0.05), and resulted in lower gut microbial richness and diversity. The diet of 1000 mg/kg BEC reduced the jejunal and ovarian pathological damage and oxidative damage, increased short-chain fatty acids (SCFAs) content, and enhanced gut microbial richness and diversity (p < 0.05) in laying hens challenged with C. perfringens and coccidia. Furthermore, the positive effects of BEC on intestinal health were associated with changes in gut microbial composition and structure. In summary, dietary supplementation with BEC has the potential to reduce the severity of intestinal and ovarian damage caused by challenges posed by C. perfringens and coccidia through the modulation of gut microbiota.

Obesity is a chronic, multifactorial disease characterized by persistent low-grade tissue and systemic inflammation. Fat accumulation in adipose tissue (AT) leads to stress and dysfunctional adipocytes, along with the infiltration of immune cells, which initiates and sustains inflammation. Neutrophils are the first immune cells to infiltrate AT during high-fat diet (HFD)-induced obesity. Emerging evidence suggests that the formation and release of neutrophil extracellular traps (NETs) play a significant role in the progression of obesity and related diseases. Additionally, obesity is associated with an imbalance in gut microbiota and increased intestinal barrier permeability, resulting in the translocation of live bacteria, bacterial deoxyribonucleic acid (DNA), lipopolysaccharides (LPS), and pro-inflammatory cytokines into the bloodstream and AT, thereby contributing to metabolic inflammation. Recent research has also shown that short-chain fatty acids (SCFAs), produced by gut microbiota, can influence various functions of neutrophils, including their activation, migration, and the generation of inflammatory mediators. This review comprehensively summarizes recent advancements in understanding the role of neutrophils and NET formation in the pathophysiology of obesity and related disorders while also focusing on updated potential therapeutic approaches targeting NETs based on studies conducted in humans and animal models.

Gut microbiota regulates the immune system, the development and progression of autoimmune diseases (AIDs) and overall health. Recent studies have played a crucial part in understanding the specific role of different gut bacterial strains and their metabolites in different AIDs. Microbial signatures in AIDs are revealed by advanced sequencing and metabolomics studies. Microbes such as Faecalibacterium prausnitzii, Akkermansia muciniphila, Anaerostipes caccae, Bacteroides sp., Roseburia sp., Blautia sp., Blautia faecis, Clostridium lavalense, Christensenellaceae sp., Coprococcus sp., Firmicutes sp., Ruminococcaceae sp., Lachnospiraceae sp., Megamonas sp., Monoglobus sp., Streptococcus pneumoniae and Bifidobacterium sp. help maintain immune homeostasis; whereas, Prevotella copri, Ruminococcus gnavus, Lactobacillus salivarius, Enterococcus gallinarum, Elizabeth menigoseptica, Collinsella sp., Escherichia sp., Fusobacterium sp., Enterobacter ludwigii, Enterobacteriaceae sp., Proteobacteria, Porphyromonas gingivalis, Porphyromonas nigrescens, Dorea sp., and Clostridium sp. cause immuno-pathogenesis. A complex web of interactions is revealed by understanding the influence of gut microbiota on immune cells and various T cell subsets such as CD4+ T cells, CD8+ T cells, natural killer T cells, γδ T cells, etc. Certain AIDs, including rheumatoid arthritis, diabetes mellitus, atopic asthma, inflammatory bowel disease and non-alcoholic fatty liver disease exhibit a state of dysbiosis, characterized by alterations in microbial diversity and relative abundance of specific taxa. This review summarizes recent developments in understanding the role of certain microbiota composition in specific AIDs, and the factors affecting specific regulatory T cells through certain microbial metabolites and also focuses the potential application and therapeutic significance of gut microbiota-based interventions as novel adjunctive therapies for AIDs. Further research to determine the precise association of each gut bacterial strain in specific diseases is required.

The East Friesian sheep is a dairy breed known for its high fertility and high milk production and is currently one of the best dairy sheep breeds in the world. This breed is known to have a poor disease-resistant phenotype compared to Hu sheep. Gut microbiota and metabolites play a role in host disease resistance. The intestinal bacterial microbiota is essential for maintaining the health of sheep and ensuring their productive potential, and it may also help explain disease-resistant phenotypic differences related to breeds. However, the ileum microbiota and metabolite profiles of Hu sheep and East Friesian sheep have remained poorly characterized. The ileal is a significant organ in the intestinal tract, and most nutrients and minerals in food are absorbed through the small intestine. It is necessary to understand the composition of both species' ileal microbiota and metabolites using the same feeding conditions. Therefore, studying the differences in the ileal microorganisms between breeds is essential to decipher the mechanisms behind these differences and identify microorganisms that influence the disease-resistant phenotype drive of ruminants. Due to the poor disease-resistant phenotype in sheep during the weaning period, with diarrhea and other diseases most likely to occur, we selected dairy sheep that were just two months old and had recently been weaned. This study comprehensively examined differences between the ileal microbiota in a large cohort of two breeds of sheep, including six Hu sheep and six East Friesian sheep. Using 16S rRNA and non-targeted metabolomics analysis, we determined that the Hu sheep had more microorganisms, including Lactobacillus, Bifidobacterium, Streptococcus, and Limmosilactobacillus, and more metabolites, including 2,7-Dihydroxy-5-methyl-1-naphthoic acid, Leu-Pro-Glu-Phe-Tyr, dodecanoic acid, Ala-Gln-Phe-Ile-Met, and Ala-Gln-Glu-Val-His, compared to the EF sheep group. Moreover, the Hu sheep were significantly enriched in amino acid biosynthesis, fatty acid metabolites, and bile secretion compared to the EF sheep groups, which may have been the main driver of the observed differences in disease-resistant phenotypes between the Hu sheep and East Friesian sheep. In addition, we hypothesized that there may be multiple beneficial microbes and metabolites that modulate the immune response and ultimately affect disease resistance. Therefore, these findings provide insights into the mechanisms underlying disease-resistant phenotype in sheep and may provide useful information for optimizing the composition of the ileal bacterial microbiota in sheep.

Inflammatory bowel disease (IBD) affects over 7 million people worldwide and significant side effects are associated with current therapies such as tofacitinib citrate (TFC), which is linked to increased risks of malignancy and congestive heart issues. To mitigate these systemic adverse effects, localised drug delivery via nano-sized carriers to inflamed gut tissues represents a promising approach. Herein, we aimed to optimise the synthesis of nanoparticles (NPs) using a low molecular weight grade of Poly(lactic-co-glycolic acid) (PLGA) 50:50 loaded with TFC. This approach leverages the dual anti-inflammatory action of TFC and the local production of anti-inflammatory short-chain fatty acids from the degradation of PLGA by colonic gut microbiota. NPs were produced by nanoprecipitation and characterised for their drug release profile in vitro. The efficacy of the enhanced PLGA-TFC NPs was then tested in a C57BL/6 DSS colitis mouse model. The release profile of TFC from the enhanced PLGA NPs showed a 40% burst release within the first hour, followed by up to 80% drug release in the colonic environment. Notably, the degradation of PLGA by colonic gut microbiota did not significantly influence TFC release. In the mouse model, neither PLGA NPs alone nor TFC alone showed significant effects on weight loss compared to the TFC-loaded PLGA NPs, emphasising the enhanced efficacy potential of the combined formulation. Altogether, these results suggest a promising role of NP delivery systems in enhancing TFC efficacy, marking a significant step towards reducing dosage and associated side effects in IBD treatment. This study underscores the potential of PLGA-TFC NPs in providing targeted and effective therapy for IBD.

This study explores the effects of dietary supplementation with passion fruit peel pectin (Passiflora edulis) and red yeast cell walls (Sporidiobolus pararoseus) on growth performance, immunity, intestinal morphology, gene expression, and gut microbiota of Nile tilapia (Oreochromis niloticus). Nile tilapia with an initial body weight of approximately 15 ± 0.06 g were fed four isonitrogenous (29.09-29.94%), isolipidic (3.01-4.28%), and isoenergetic (4119-4214 Cal/g) diets containing 0 g kg-1 pectin or red yeast cell walls (T1 - Control), 10 g kg-1 pectin (T2), 10 g kg-1 red yeast (T3), and a combination of 10 g kg-1 pectin and 10 g kg-1 red yeast (T4) for 8 weeks. Growth rates and immune responses were assessed at 4 and 8 weeks, while histology, relative immune and antioxidant gene expression, and gut microbiota analysis were conducted after 8 weeks of feeding. The results showed that the combined supplementation (T4) significantly enhanced growth performance metrics, including final weight, weight gain, specific growth rate, and feed conversion ratio, particularly by week 8, compared to T1, T2, and T3 (P < 0.05). Immunological assessments revealed increased lysozyme and peroxidase activities in both skin mucus and serum, with the T4 group showing the most pronounced improvements. Additionally, antioxidant and immune-related gene expression, including glutathione peroxidase (GPX), glutathione reductase (GSR), and interleukin-1 (IL1), were upregulated in the gut, while intestinal morphology exhibited improved villus height and width. Gut microbiota analysis indicated increased alpha and beta diversity, with a notable rise in beneficial phyla such as Actinobacteriota and Firmicutes in the supplemented groups. These findings suggest that the combined use of pectin and red yeast cell walls as prebiotics in aquaculture can enhance the health and growth of Nile tilapia, offering a promising alternative to traditional practices. Further research is needed to determine optimal dosages for maximizing these benefits.

The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.

Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota-derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine-N-oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined.

Systemic lupus erythematosus (SLE) is known as an autoimmune disorder that is characterized by the breakdown of self-tolerance, resulting in disease onset and progression. Macrophages have been implicated as a factor in the development of SLE through faulty phagocytosis of dead cells or an imbalanced M1/M2 ratio. The study aimed to investigate the immunomodulatory effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on M1 and M2 macrophages in new case lupus patients. For this purpose, blood monocytes were collected from lupus patients and healthy people and were cultured for 5 days to produce macrophages. For 48 h, the macrophages were then cocultured with either probiotics or lipopolysaccharides (LPS). Flow cytometry and real-time polymerase chain reaction were then used to analyze the expression of cluster of differentiation (CD) 14, CD80, and human leukocyte antigen - DR (HLADR) markers, as well as cytokine expression (interleukin [IL]1-β, IL-12, tumor necrosis factor α [TNF-α], IL-10, and transforming growth factor beta [TGF-β]). The results indicated three distinct macrophage populations, M0, M1, and M2. In both control and patient-derived macrophage-derived monocytes (MDMs), the probiotic groups showed a decrease in CD14, CD80, and HLADR expression compared to the LPS group. This decrease was particularly evident in M0 and M2 macrophages from lupus patients and M1 macrophages from healthy subjects. In addition, the probiotic groups showed increased levels of IL-10 and TGF-β and decreased levels of IL-12, IL1-β, and TNF-α in MDMs from both healthy and lupus subjects compared to the LPS groups. Although there was a higher expression of pro-inflammatory cytokines in lupus patients, there was a higher expression of anti-inflammatory cytokines in healthy subjects. In general, L. delbrueckii and L. rhamnosus could induce anti-inflammatory effects on MDMs from both healthy and lupus subjects.

The pathogenesis of age-related macular degeneration (AMD), a degenerative retinopathy, remains unclear. Administration of anti-vascular endothelial growth factor agents, antioxidants, fundus lasers, photodynamic therapy, and transpupillary warming has proven effective in alleviating symptoms; however, these interventions cannot prevent or reverse AMD. Increasing evidence suggests that AMD risk is linked to changes in the composition, abundance, and diversity of the gut microbiota (GM). Activation of multiple signaling pathways by GM metabolites, including lipopolysaccharides, oxysterols, short-chain fatty acids (SCFAs), and bile acids (BAs), influences retinal physiology. Traditional Chinese medicine (TCM), known for its multi-component and multi-target advantages, can help treat AMD by altering GM composition and regulating the levels of certain substances, such as lipopolysaccharides, reducing oxysterols, and increasing SCFA and BA contents. This review explores the correlation between GM and AMD and interventions for the two to provide new perspectives on treating AMD with TCM.

Dietary nutrients and the gut microbiota are increasingly recognized to cross-regulate and entrain each other, and thus affect host health and immune-mediated diseases. Here, we systematically review the current understanding linking dietary nutrients to gut microbiota-host immune interactions, emphasizing how this axis might influence host immunity in health and diseases. Of relevance, we highlight that the implications of gut microbiota-targeted dietary intervention could be harnessed in orchestrating a spectrum of immune-associated diseases.

Despite the important role of gut microbiota in the maturation of the immune system, little is known about its impact on the development of T-cell responses to vaccination. Here, we immunized C57BL/6 mice with a prime-boost regimen using DNA plasmid, the Chimpanzee Adenovirus, and the modified Vaccinia Ankara virus expressing a candidate HIV T-cell immunogen and compared the T-cell responses between individuals with an intact or antibiotic-depleted microbiota. Overall, the depletion of the gut microbiota did not result in significant differences in the magnitude or breadth of the immunogen-specific IFNγ T-cell response after vaccination. However, we observed marked changes in the serum levels of four cytokines after vaccinating microbiota-depleted animals, particularly a significant reduction in IL-22 levels. Interestingly, the level of IL-22 in serum correlated with the abundance of Roseburia in the large intestine of mice in the mock and vaccinated groups with intact microbiota. This short-chain fatty acid (SCFA)-producing bacterium was significantly reduced in the vaccinated, microbiota-depleted group. Therefore, our results indicate that, although microbiota depletion reduces serum levels of IL-22, the powerful vaccine regime used could have overcome the impact of microbiota depletion on IFNγ-producing T-cell responses.

Studies have demonstrated that propionate metabolism-related genes (PMRGs) are associated with cancer progression. PMRGs are not known to be involved in Hepatocellular carcinoma (HCC).

In this study, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were accessed for HCC-related transcriptome data and clinical information. First, DE-PMRGs were derived by intersecting PMRGs and DEGs between HCC tissues and normal controls. The clusterProfiler R package was then used to enrich DE-PMRGs. In addition, biomarkers of HCC were identified, and a prognostic model was developed. Using functional analysis and tumor microenvironment analysis, new insights were obtained into HCC. The expression of biomarkers was validated using quantitative real-time polymerase chain reaction (qRT-PCR).

132 DE-PMRGs were obtained by intersecting 3690 DEGs and 291 PMRGs. Steroid and organic acid metabolism were associated with these genes. For the construction of the risk model for HCC samples, five biomarkers were identified, including Acyl-CoA dehydrogenase short chain (ACADS), CYP19A1, formiminotransferase cyclodeaminase (FTCD), glucose-6-phosphate dehydrogenase (G6PD), and glutamic-oxaloacetic transaminase (GOT2). ACADS, FTCD, and GOT2 were positive factors, whereas CYP19A1 and G6PD were negative. HCC patients with AUC greater than 0.6 were predicted to survive 1/2/3/4/5 years, indicating decent efficiency of the model. The probability of 1/3/5-survival for HCC was also predicted by the nomogram using the risk score, pathologic T stage, and cancer status. Moreover, functional enrichment analysis revealed the high-risk genes were associated with invasion and epithelial-mesenchymal transition. Significantly, immune cell infiltration and immune checkpoint expression were linked to HCC development.

This study identified five biomarkers of propionate metabolism that can predict HCC prognosis. This finding may provide a deeper understanding of PMRG function in HCC.

Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease. Gut dysbiosis is considered a significant contributing factor in disease development. Increased intestinal permeability can be induced by gut dysbiosis, followed by the entry of lipopolysaccharide into circulation to reach peripheral tissue and result in chronic inflammation. We reviewed how microbial metabolites push host physiology toward MAFLD, including short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites. The effects of SCFAs are generally reported as anti-inflammatory and can improve intestinal barrier function and restore gut microbiota. Gut microbes can influence intestinal barrier function through SCFAs produced by fermentative bacteria, especially butyrate and propionate producers. This is achieved through the activation of free fatty acid sensing receptors. Bile is directly involved in lipid absorption. Gut microbes can alter bile acid composition by bile salt hydrolase-producing bacteria and bacterial hydroxysteroid dehydrogenase-producing bacteria. These bile acids can affect host physiology by activating farnesoid X receptor Takeda G protein-coupled receptor 5. Gut microbes can also induce MAFLD-associated symptoms by producing tryptophan metabolites kynurenine, serotonin, and indole-3-propionate. A summary of bacterial genera involved in SCFAs production, bile acid transformation, and tryptophan metabolism is provided. Many bacteria have demonstrated efficacy in alleviating MAFLD in animal models and are potential therapeutic candidates for MAFLD.

Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis.

A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes.

Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend <0.05) but not for type I tumors. The associations of smoking with increased odds of colorectal neoplasm significantly differed by gut microbiota enterotypes (p<0.05 for heterogeneity). An increase in carcinogenic bacteria (genus Escherichia shigella) and a decrease in probiotics (family Lachnospiraceae and Ruminococcaceae) in type II tumors may drive disease progression by upregulating oncogenic signaling pathways and inflammatory/oxidative stress response pathways, as well as protein phospholipase D1/2, cytochrome C, and prostaglandin-endoperoxide synthase 2 expression.

Smoking was associated with a higher odds of type II colorectal neoplasms but not type I tumors, supporting a potential role for the gut microbiota in mediating the association between smoking and colorectal neoplasms.

Given the increasing concerns regarding greenhouse gas emissions associated with livestock production, the need to discover effective strategies to mitigate methane production in ruminants is clear. Marine algal polysaccharides have emerged as a promising research avenue because of their abundance and sustainability. Polysaccharides, such as alginate, laminaran, and fucoidan, which are extracted from marine seaweeds, have demonstrated the potential to reduce methane emissions by influencing the microbial populations in the rumen. This comprehensive review extensively examines the available literature and considers the effectiveness, challenges, and prospects of using marine seaweed polysaccharides as feed additives. The findings emphasise that marine algal polysaccharides can modulate rumen fermentation, promote the growth of beneficial microorganisms, and inhibit methanogenic archaea, ultimately leading to decreases in methane emissions. However, we must understand the long-term effects and address the obstacles to practical implementation. Further research is warranted to optimise dosage levels, evaluate potential effects on animal health, and assess economic feasibility. This critical review provides insights for researchers, policymakers, and industry stakeholders dedicated to advancing sustainable livestock production and methane mitigation.

The pathogenesis of asthma has been partially linked to lung and gut microbiome. We utilized a steroid-resistant chronic model of cockroach antigen-induced (CRA) asthma with corticosteroid (fluticasone) treatment to examine lung and gut microbiome during disease. The pathophysiology assessment demonstrated that mucus and airway hyperresponsiveness were increased in the chronic CRA with no alteration in the fluticasone (Flut)-treated group, demonstrating steroid resistance. Analysis of mRNA from lungs showed no decrease of MUC5AC or Gob5 in the Flut-treated group. Furthermore, flow-cytometry in lung tissue showed eosinophils and neutrophils were not significantly reduced in the Flut-treated group compared to the chronic CRA group. When the microbiome profiles were assessed, data showed that only the Flut-treated animals were significantly different in the gut microbiome. Finally, a functional analysis of cecal microbiome metabolites using PiCRUSt showed several biosynthetic pathways were significantly enriched in the Flut-treated group, with tryptophan pathway verified by ELISA with increased kynurenine in homogenized cecum samples. While the implications of these data are unclear, they may suggest a significant impact of steroid treatment on future disease pathogenesis through microbiome and associated metabolite pathway changes.

The COVID-19 pandemic has had a profound impact worldwide, resulting in long-term health effects for many individuals. Recently, as more and more people recover from COVID-19, there is an increasing need to identify effective management strategies for post-COVID-19 syndrome, which may include diarrhea, fatigue, and chronic inflammation. Oligosaccharides derived from natural resources have been shown to have prebiotic effects, and emerging evidence suggests that they may also have immunomodulatory and anti-inflammatory effects, which could be particularly relevant in mitigating the long-term effects of COVID-19. In this review, we explore the potential of oligosaccharides as regulators of gut microbiota and intestinal health in post-COVID-19 management. We discuss the complex interactions between the gut microbiota, their functional metabolites, such as short-chain fatty acids, and the immune system, highlighting the potential of oligosaccharides to improve gut health and manage post-COVID-19 syndrome. Furthermore, we review evidence of gut microbiota with angiotensin-converting enzyme 2 expression for alleviating post-COVID-19 syndrome. Therefore, oligosaccharides offer a safe, natural, and effective approach to potentially improving gut microbiota, intestinal health, and overall health outcomes in post-COVID-19 management.

5-Fluorouracil (5-FU) is a common anti-tumor drug, but there is no effective treatment for its side effect, intestinal mucositis. The inflammatory reaction of macrophages in intestinal mucosa induced by 5-FU is an important cause of intestinal mucositis. In this study, we investigated the anti-inflammatory effects of the three important short-chain fatty acids (SCFAs), including sodium acetate (NaAc), sodium propionate (NaPc), and sodium butyrate (NaB), on human mononuclear macrophage-derived THP-1 cells induced by 5-FU. The expressions of intracellular ROS, pro-inflammatory/anti-inflammatory cytokines, as well as the nuclear factor-κB/NLR family and pyrin domain-containing protein 3 (NF-κB/NLRP3) signaling pathway proteins were determined. Furthermore, the cell metabolites were analyzed by untargeted metabolomics techniques. Our results revealed that the three SCFAs inhibited pro-inflammatory factor expressions, including IL-1β and IL-6, when treated with 5-FU (p < 0.05). The ROS expression and NF-κB activity of 5-FU-treated THP-1 cells were inhibited by the three SCFAs pre-incubated (p < 0.05). Moreover, NLRP3 knockdown abolished 5-FU-induced IL-1β expression (p < 0.05). Further experiments showed that the three SCFAs affected 20 kinds of metabolites that belong to amino acid and phosphatidylcholine metabolism in THP-1 cells. These significantly altered metabolites were involved in amino acid metabolism and glycerolphospholipid and sphingolipid metabolism. It is the first time that three important SCFAs (NaAc, NaPc, and NaB) were identified as inhibiting 5-FU-induced macrophage inflammation through inhibiting ROS/NF-κB/NLRP3 signaling pathways and regulating glycerolphospholipid and sphingolipid metabolism.

Diarrhea is a severe bovine disease, globally prevalent in farm animals with a decrease in milk production and a low fertility rate. Cryptosporidium spp. are important zoonotic agents of bovine diarrhea. However, little is known about microbiota and short-chain fatty acids (SCFAs) changes in yaks infected with Cryptosporidium spp. Therefore, we performed 16S rRNA sequencing and detected the concentrations of SCFAs in Cryptosporidium-infected yaks. Results showed that over 80,000 raw and 70,000 filtered sequences were prevalent in yak samples. Shannon (p<0.01) and Simpson (p<0.01) were both significantly higher in Cryptosporidium-infected yaks. A total of 1072 amplicon sequence variants were shared in healthy and infected yaks. There were 11 phyla and 58 genera that differ significantly between the two yak groups. A total of 235 enzymes with a significant difference in abundance (p<0.001) were found between healthy and infected yaks. KEGG L3 analysis discovered that the abundance of 43 pathways was significantly higher, while 49 pathways were significantly lower in Cryptosporidium-infected yaks. The concentration of acetic acid (p<0.05), propionic acid (p<0.05), isobutyric acid (p<0.05), butyric acid (p<0.05), and isovaleric acid was noticeably lower in infected yaks, respectively. The findings of the study revealed that Cryptosporidium infection causes gut dysbiosis and results in a significant drop in the SCFAs concentrations in yaks with severe diarrhea, which may give new insights regarding the prevention and treatment of diarrhea in livestock.

Food allergy has caused lots of global public health issues, particularly in developed countries. Presently, gut microbiota has been widely studied on allergy, while the role of dysbiosis in food allergy remains unknown. Scientists found that changes in gut microbial compositions and functions are strongly associated with a dramatic increase in the prevalence of food allergy. Altering microbial composition is crucial in modulating food antigens' immunogenicity. Thus, the potential roles of probiotics, prebiotics, synbiotics, and postbiotics in affecting gut bacteria communities and the immune system, as innovative strategies against food allergy, begins to attract high attention of scientists. This review briefly summarized the mechanisms of food allergy and discussed the role of the gut microbiota and the use of probiotics, prebiotics, synbiotics, and postbiotics as novel therapies for the prevention and treatment of food allergy. The perspective studies on the development of novel immunotherapy in food allergy were also described. A better understanding of these mechanisms will facilitate the development of preventive and therapeutic strategies for food allergy.

In order to develop properly, the brain requires the intricate interconnection of genetic factors and pre-and postnatal environmental events. The gut-brain axis has recently raised considerable interest for its involvement in regulating the development and functioning of the brain. Consequently, alterations in the gut microbiota composition, due to antibiotic administration, could favor the onset of neurodevelopmental disorders. Literature data suggest that the modulation of gut microbiota is often altered in individuals affected by neurodevelopmental disorders. It has been shown in animal studies that metabolites released by an imbalanced gut-brain axis, leads to alterations in brain function and deficits in social behavior. Here, we report the potential effects of antibiotic administration, before and after birth, in relation to the risk of developing neurodevelopmental disorders. We also review the potential role of probiotics in treating gastrointestinal disorders associated with gut dysbiosis after antibiotic administration, and their possible effect in ameliorating neurodevelopmental disorder symptoms.

Metabolic syndrome (MS) comprises a vast range of metabolic dysfunctions, which can be associated to cardiovascular disease risk factors. MS is reaching pandemic levels worldwide and it currently affects around 25% in the adult population of developed countries. The definition states for the diagnosis of MS may be clear, but it is also relevant to interpret the patient data and realize whether similar criteria were used by different clinicians. The different criteria explain, at least in part, the controversies on the theme. Several studies are presently focusing on the microbiota changes according to the components of MS. It is widely accepted that the gut microbiota is a regulator of metabolic homeostasis, being the gut microbiome in MS described as dysbiotic and certain taxonomic groups associated to metabolic changes. Probiotics, and more recently synbiotics, arise as promising therapeutic alternatives that can mitigate some metabolic disturbances, namely by correcting the microbiome and bringing homeostasis to the gut. The most recent studies were revised and the promising results and perspectives revealed in this review.