Inflammatory Bowel Disease (IBD) is a spectrum of chronic inflammatory diseases of the intestine that includes subtypes of ulcerative colitis (UC) and Crohn's Disease (CD) and currently has no cure. While IBD results from a complex interplay between genetic, environmental, and immunological factors, sequencing advances over the last 10-15 years revealed signature changes in gut microbiota that contribute to the pathogenesis of IBD. These findings highlight IBD as a disease target for microbiome-based therapies, with the potential to treat the underlying microbial pathogenesis and provide adjuvant therapy to the emerging spectrum of advanced therapies for IBD. Building on the success of fecal microbiota transplantation (FMT) for Clostridioides difficile infection, therapies targeting gut microbiota have emerged as promising approaches for treating IBD; however, unique aspects of IBD pathogenesis highlight the need for more precision in the approach to microbiome therapeutics that leverage aspects of recipient and donor selection, diet and xenobiotics, and strain-specific interactions to enhance the efficacy and safety of IBD therapy. This review focuses on both pre-clinical and clinical studies that support the premise for microbial therapeutics for IBD and aims to provide a framework for the development of precision microbiome therapeutics to optimize clinical outcomes for patients with IBD.

The gut microbiome plays a key role in human health, influencing various biological processes and disease outcomes. The historical roots of probiotics are traced back to Nobel Laureate Élie Metchnikoff, who linked the longevity of Bulgarian villagers to their consumption of sour milk fermented by Lactobacilli. His pioneering work led to the global recognition of probiotics as beneficial supplements, now a multibillion-dollar industry. Modern probiotics have been extensively studied for their immunomodulatory effects. Limosilactobacillus reuteri (L. reuteri), a widely used probiotic, has garnered significant attention for its systemic immune-regulatory properties, particularly in relation to autoimmunity and cancer. This review delves into the role of L. reuteri in modulating immune responses, with a focus on its impact on systemic diseases.

Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the interactome concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites. Meanwhile, this review also aims to present an updated overview of the relevant mechanisms, high-throughput multi-omics methodologies, different types of multi-omics cohort resources, and computational methods used to understand host-microbiota interactions in the context of IBD. Finally, we discuss the challenges pertaining to the integration of multi-omics data in order to reveal host-microbiota cross-talk and offer insights into relevant future research directions.

Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

Diet has a profound impact in human health, which is partly driven by changes in the intestinal microbiota. Several associations between dietary intake and the intestinal microbiota composition and function have been described. Namely, the Mediterranean diet is associated with beneficial bacteria, while the intake of ultraprocessed foods is linked to dysbiosis. It is, therefore, very tempting to tailor dietary approaches to the individual needs of the microbiota; however, high-quality prospective data are lacking. Provisionally, a diet rich in fruits and vegetables and low in ultraprocessed foods is recommended to improve the intestinal microbiota composition and function.

Age-related macular degeneration (AMD) is one of the most prevalent eye diseases among the ageing population worldwide. It is a leading cause of blindness in individuals over 55, particularly in industrialised Western countries. The prevalence of AMD increases with age, and genetic factors and environmental influences are believed to contribute to its development. Among the environmental factors, diet plays a significant role in AMD. This review explores the association between dietary components, dietary patterns and AMD. Various nutrients, non-nutrient substances and dietary models that have the potential to counteract oxidative stress and inflammation, which are underlying mechanisms of AMD, are discussed. Consuming fruits, vegetables, fish and seafood, whole grains, olive oil, nuts and low-glycaemic-index foods has been highlighted as beneficial for reducing the risk of AMD. Adhering to the Mediterranean diet, which encompasses these elements, can be recommended as a dietary pattern for AMD. Furthermore, the modulation of the gut microbiota through dietary interventions and probiotics has shown promise in managing AMD.

The influence of the gut microbiome on the human brain, especially its associations with psychiatric disorders, has emerged as a focal area in contemporary neuroscience and psychiatry research. In this study, we employed a mediation Mendelian randomization approach to delve into the potential causal relationships between gut microbiota and psychiatric disorders, with a focus on the mediating role of brain structural changes. We harnessed genetic data from large - scale genome - wide association studies to analyze how 196 gut microbiota taxa affect ten psychiatric disorders via alterations in 3143 brain structures. Our key findings revealed significant bidirectional causal relationships. In the gut microbiota - brain structure relationship, certain gut microbiota taxa, such as Bacteroides and Marvinbryantia, were associated with changes in brain activity and white matter integrity respectively. Conversely, brain structures like the right hippocampus and left superior cerebellar peduncle influenced gut microbiota composition. Regarding gut microbiota and psychiatric disorders, we identified numerous associations. For example, the genus Prevotellaceae was significantly associated with an increased risk of Autism Spectrum Disorder, while Ruminococcaceae UCG005 showed a protective effect. In Panic Disorder, Alistipes was positively associated, and for Schizophrenia, both protective (Barnesiella) and risk - associated (Phascolarctobacterium) genera were found. Moreover, through mediation analysis, we found that brain structures mediated the effects of gut microbiota on five psychiatric disorders, including bipolar disorder and anorexia nervosa. In these cases, the influence of gut microbiota on the disorders was fully transmitted through changes in brain structure. Overall, our research clarifies the role of the microbiota - gut - brain axis in mental health. It offers a new perspective on how intestinal microbes impact brain physiology and psychiatric pathology. These findings not only deepen our understanding of the biological interactions between the gut and brain but also suggest that targeted gut microbiota modifications could be novel therapeutic strategies for mental health disorders.

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental disorder that often persists into adulthood, leading to various adverse outcomes. Its underlying pathology is multifactorial, involving neurotransmitter imbalances, gut microbiota alterations, and oxidative and inflammatory dysregulation. Diet, a key environmental modifier of gut ecology, is consistently poorer in individuals with ADHD, with multiple nutrients implicated in its pathophysiology. This review examines the role of specific nutrients such as omega-3 fatty acids, key micronutrients, and potentially harmful dietary components, as well as broader dietary patterns, particularly the Western diet and Mediterranean diet (MedDiet), in relation to ADHD symptoms. It also evaluates both whole-diet and supplement-based clinical interventions, supporting the growing recognition of nutrition as a safe and relatively affordable modifiable factor in ADHD management. Additionally, the biological mechanisms linking diet to ADHD are reviewed, highlighting strong evidence for the involvement of gut dysbiosis and inflammatory processes. Despite the well-documented antioxidant, anti-inflammatory, and microbiome benefits of the MedDiet, direct research investigating its role in ADHD remains limited. Most whole-diet approaches to date have focused on elimination diets, leaving a significant gap in understanding the potential role of the MedDiet in ADHD management. Therefore, this review outlines preliminary evidence supporting the MedDiet and its key components as modulators of ADHD-related biological pathways, indicating its potential as a therapeutic approach. However, further research is required to rigorously evaluate its clinical efficacy. Finally, the limitations of observational and interventional nutritional research in ADHD are discussed, along with recommendations for future research directions.

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health vs IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

The intestinal microbiota plays a crucial role in maintaining host health by participating in various beneficial functions. However, under certain conditions, it can contribute to the development of inflammatory bowel disease (IBD) and other chronic inflammatory conditions. Importantly, not all commensal microbiota members are drivers of inflammation. A specific subset of commensal bacteria, known as pathobionts, can exhibit pathogenic potential under specific circumstances. Their inflammatory potential is modulated by several factors, including the host's genetic background and the surrounding microbiota. Furthermore, diet has emerged as a critical factor influencing the gut microbiota, with some studies highlighting its role in modulating pathobionts. This review will delve into the role played by pathobionts in chronic intestinal inflammation, in both mouse models as well as in humans, with a focus on the interplay between dietary factors and pathobiont members of the intestinal microbiota. Understanding the complex relationships between diet, pathobionts, and chronic inflammation could pave the way for diet-based therapeutic strategies aimed at managing chronic inflammatory conditions.

Anxiety disorders are mental health disorders characterized by long-lasting fear, worry, nervousness, and alterations in gut microbiota (GM). The GM is a vital modulator of brain function through the gut-brain axis, which acts as the neural pathway between the central and peripheral nervous systems. Dysbiosis of GM plays an essential role in anxiety development because of alterations in the vagus nerve, increased intestinal permeability, and altered breakdown of tryptophan (TRP). The Kynurenine (KYN) pathway plays a crucial role in the pathogenesis of anxiety disorders, primarily through its neuroprotective (KYNA) and neurotoxic (QUIN) metabolites. Higher ratios of KYNA/QUIN result in neuroprotection, whereas higher KYN/TRP ratios indicate increased QUIN production causing neuroinflammation. Studies on germ-free models exhibit higher plasma TRP levels, which interrupt the metabolic balance of TRP-derived compounds, thus causing brain impairment. A key issue in anxiety disorders is the dysregulation of GM, which disrupts TRP metabolism and neuroinflammatory pathways, however, remains poorly understood. Hence, the proper understanding of these mechanisms is crucial for future therapeutic advancements. Here, we highlight the significance of the TRP-KYN pathway and the potential of modulating KYN pathway enzymes, such as kynurenine aminotransferases (KATs), to adjust KYNA levels and restore neurotransmitter balance. It further discusses new therapeutic methods with a particular focus on probiotics that may restore GM and modulate TRP metabolism. Advancing our understanding of the intricate relationship between GM and anxiety disorders may facilitate novel, microbiota-targeted interventions. This ultimately contributes to precision medicine approaches in mental health care, thereby enhancing treatment efficacy and patient outcomes.

Hand osteoarthritis (OA) is a prevalent and disabling condition, yet its pathogenesis remains less studied than OA in large weight-bearing joints. Emerging genetic, epigenetic, and microbiome research suggests that hand OA might be biologically distinct, involving joint-specific pathways not shared by knee or hip OA. This review integrates genome-wide association studies specific to hand OA, highlighting key molecular contributors such as inflammatory cytokines. These genetic insights, together with emerging data on epigenetic alterations and gut microbial dysbiosis, point to broader systemic and regulatory influences on hand OA onset and progression. We also assess pharmacologic interventions tested in randomized controlled trials that have attempted to target these pathways. While agents such as TNF and IL-6 inhibitors, hydroxychloroquine, and corticosteroids have shown limited success, emerging evidence supports the potential of methotrexate in synovitis-positive general hand OA, platelet-rich plasma in thumb carpometacarpal (CMC) OA, and prolotherapy in interphalangeal (IP) OA. These findings illustrate the persistent gap between mechanistic understanding and therapeutic success. Future work must prioritize multifactorial strategies for addressing pain and translational frameworks that link molecular mechanisms to treatment response. In summary, this review offers an update on hand OA and identifies key opportunities for more targeted and effective therapy.

The gut microbiota confers host protection against pathogen colonization early after infection. Several mechanisms underlying the protection have been described, but the contributions of nutrient competition versus direct inhibition are controversial. Using an ex vivo model of Salmonella growth in the mouse cecum with its indigenous microbes, we find that nutrient limitation and typical inhibitory factors alone cannot prevent pathogen growth. However, the addition of certain amino acids markedly reverses the microbiota's ability to suppress pathogen growth. Enhanced Salmonella colonization after antibiotic treatment is ablated by exclusion of dietary protein, which requires the presence of the microbiota. Thus, dietary protein and amino acids are important regulators of colonization resistance.

Stroke-associated pneumonia (SAP), a highly lethal complication following stroke, is closely linked to dysregulation of the "brain-gut-lung axis." Accumulating evidence indicates that stroke triggers intestinal alterations through the brain-gut axis, while multiple studies confirm that gut-derived changes can mediate pneumonia through the gut-lung axis. However, the mechanisms connecting stroke-induced intestinal dyshomeostasis to SAP remain incompletely elucidated, and the multiorgan interaction mechanisms of the "brain-gut-lung axis" in SAP pathogenesis require further exploration.

This systematic literature review systematically searched databases, including PubMed, using the keywords "stroke," "gastrointestinal microbiome," and "bacterial pneumonia," incorporating 80 mechanistic studies. Key findings reveal that stroke initiates a cascade of "neuro-microbial-immune" pathway interactions along the brain-gut-lung axis, leading to intestinal dyshomeostasis characterized by microbiota and metabolite alterations, barrier disruption, immune dysregulation, inflammatory responses, and impaired gut motility. These intestinal perturbations ultimately disrupt pulmonary immune homeostasis, promoting SAP development. In addition, stroke directly induces vagus nerve injury through the brain-gut axis, resulting in impaired swallowing and cough reflexes that exacerbate aspiration-related pulmonary infection risks.

Elucidating the role of the brain-gut-lung axis in SAP pathogenesis provides critical insights into its underlying mechanisms. This paradigm highlights intestinal homeostasis modulation and vagus nerve stimulation as promising therapeutic strategies for SAP prevention and management, advancing a multitargeted approach to mitigate poststroke complications.

Exclusive Enteral Nutrition (EEN) and the Crohn's Disease Exclusion Diet (CDED) have been shown to induce remission in Crohn's disease. Low-sulphur, plant-based diets are being explored for ulcerative colitis, and wholefood, low-additive approaches are emerging as significant. Although Inflammatory Bowel Disease (IBD) patients modify their diet, evidence for tolerability and benefit outside clinical trials is limited. The DELECTABLE program aimed to assess satisfaction, adherence, and efficacy of dietary therapies as part of IBD care.

In this dietitian-led, open-label, prospective study, patients with Crohn's disease were offered the CDED or a whole-food, additive-free diet (WFD), and patients with ulcerative colitis were offered a low-sulphur, plant-based diet (UCD) or WFD. Primary outcomes were 12-week diet satisfaction (modified DSAT-28) and diet adherence, including food additive intake. Secondary outcomes were quality of life (QoL) (IBDQ-9), disease activity (CDAI for Crohn's disease, partial Mayo score for ulcerative colitis), and biochemical markers (CRP, faecal calprotectin). Analyses were conducted within, rather than between, diet arms due to the non-random nature of the study. Diet adherence and disease activity change across time points (baseline, week 6, week 12) were assessed using repeated measures ANOVA or Friedman's test, with pairwise paired t-test or Wilcoxon Signed-Rank test. Diet satisfaction and quality of life changes across time (baseline/week 1, week 12) were assessed using a paired t-test or Wilcoxon Signed-Rank test.

Of 165 referrals, 76 patients enrolled, with 64 completing the 12-week program (CDED: n = 15, WFD: n = 42, UCD: n = 7). Diet satisfaction was initially high and remained stable over time on CDED (p = 0.212) and improved on WFD (p = 0.03). Patient- and dietitian-rated adherence was high at baseline and did not significantly decrease on any diet arm (p > 0.349). Food additive intake decreased on WFD (p = 0.009). QoL improved on CDED and WFD (p < 0.001). CRP, calprotectin, and CDAI were reduced on CDED (p < 0.045), and CDAI and partial Mayo were reduced on WFD (p < 0.027).

Well-balanced therapeutic diets are feasible and well-accepted by patients with IBD, with a promising impact on disease activity.

This study utilized a high-fat diet-induced obese male C57BL/6 mice model to investigate the anti-obesity and lipid-lowering effects of Lactococcus lactis subsp. lactis LL-1 and Lacticaseibacillus paracasei LP-16. A gut microbiota analysis via 16S rRNA sequencing, along with measurements of body weight, lipids, inflammation markers, and gut metabolites, revealed that lactic acid bacteria (LAB) significantly reduced body weight, blood lipid levels, and liver oxidative stress. They also enhanced gut microbiota diversity and evenness, potentially by modulating the Firmicutes/Bacteroidetes ratio to limit excess energy absorption. Malondialdehyde (MDA) showed extremely significant positive correlations with Lachnospiraceae, Blautia, and Colidextribacter, and a significant positive correlation with Helicobacter, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) exhibited opposite trends. Specifically, Muribaculaceae, Bacteroides, and Lactobacillus showed negative correlations with MDA levels and positive correlations with SOD and GSH-Px. Short-chain fatty acids (SCFAs) positively correlated with Muribaculaceae, Bacteroides, Mucispirillum, and Lactobacillus, but negatively correlated with Lachnospiraceae, Blautia, Colidextribacter, Alistipes, and Helicobacter. They increased SCFA levels by promoting beneficial bacteria and reducing pathogens, alleviating obesity and hyperlipidemia. Additionally, they regulated the gut microbiota, decreasing bile acids and long-chain fatty acids while increasing SCFAs, short peptides, and vitamins, thereby improving gut metabolic disorders and enhancing host gut health.

Emerging evidence suggests metabolic dysregulation may contribute to colorectal cancer (CRC) aetiology. We aimed to identify pre-diagnostic metabolic biomarkers for CRC risk in 230,420 UK Biobank participants.

Nuclear magnetic resonance spectroscopy was used to quantify 249 metabolic biomarkers in plasma samples collected at baseline. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CIs) for associations of metabolic biomarkers with CRC risk after adjusting for potential confounders. To infer the potential causality of biomarkers that were associated with CRC independent of the others, we performed genome-wide association analyses among 199,732 UK Biobank participants of European ancestry to identify biomarker-associated genetic variants, followed by two-sample Mendelian randomization (MR) analyses using summary statistics of 78,473 CRC cases and 107,143 controls of European ancestry.

During a median follow-up time of 9.7 years, 2,410 incident primary CRC cases were identified. Among 43 CRC-associated (P-value < 0.001) metabolic biomarkers, ten biomarkers including fatty acids (FAs), inflammation, ketone bodies, and lipoprotein lipids were associated with CRC risk after mutual adjustment. MR analyses provided strong evidence for potential causal associations of CRC risk with percentages of linolic acid [odds ratio (OR) = 0.89, 95% CI = 0.83-0.96, P-value = 3 × 10-3] and saturated FAs (OR = 1.14, 95% CI = 1.03-1.25, P-value = 9  ×  10-3) to total FAs.

We identified multiple CRC-associated metabolic biomarkers. Perturbed lipid and lipoprotein metabolism may promote colorectal carcinogenesis.

Obesity and its associated metabolic disorders─including muscle atrophy─pose significant health challenges, particularly with the increasing prevalence of high-fat diets. This study investigates the effects of nobiletin, a citrus flavonoid, on high-fat-diet-induced obesity-related muscle atrophy and its regulatory role in bile acid metabolism, aiming to determine whether nobiletin supplementation can enhance muscle mass and improve metabolic health in a mouse model. Our findings revealed that nobiletin significantly upregulated CYP7A1 expression in the liver, promoting bile acid synthesis and modulating bile acid composition in the ileum and feces, potentially through microbiota-mediated mechanisms. Furthermore, nobiletin supplementation suppressed muscle atrophy-related proteins, including p-4EBP1, TRIM63, and FBXO32, while promoting the phosphorylation of mTOR/AKT/p70S6K and FOXO3a in skeletal muscle. The FGF15/FGFR4/ERK signaling pathway was notably activated in the skeletal muscle tissues of nobiletin-supplemented mice, suggesting a protective effect against muscle atrophy despite the pathway's inhibition in the liver to promote bile acid synthesis. These results indicate that nobiletin not only mitigates muscle atrophy in the context of obesity but also enhances glucose homeostasis, likely through improved skeletal muscle function. Overall, our study highlights the potential of nobiletin as a therapeutic agent for preventing obesity-related complications, regulating bile acid metabolism, and promoting skeletal muscle health.

Metabolic disorders and complications induced by high-fat diets (HFDs) are a hot research topic in aquatic animal nutrition and health, but the mechanism of gut microbes and their metabolites on muscle homeostasis is not yet clear. In this study, a 16-week HFD (Con, 6% fat and HFD, 12% fat) rearing experiment was conducted with a freshwater drum (20.88 ± 2.75 g, about 20,000 fish per pond) to investigate the underlying regulation of gut microbes on muscle nutrient and metabolism. Results revealed that HFD had no remarkable effect on proximate nutrients (moisture, ash, crude protein, and crude fat), total amino acids, and fatty acids contents in muscle. Moreover, decreased acetic acid content by HFD in the gut and muscle was confirmed to regulate lipid metabolism, as evidenced by the activation of fatty acid synthesis (acetyl-CoA carboxylase alpha [ACC1] and sterol regulatory element binding protein-1 [SREBP1]) and inhibition of fatty acid lipolysis (AMP-activated protein kinase [AMPK], adipose triglyceride lipase [ATGL], and carnitine palmitoyl transferase 2 [CPT2]). Interestingly, RNA-seq revealed glycolytic metabolism (glycolysis/gluconeogenesis and pyruvate metabolism) was active in the muscle under HFD, which was further confirmed to be the intermediate for acetic acid to regulate lipid metabolism. Strikingly, gut microbe Rikenellaceae_RC9_gut_group and Knoellia regulate muscle lipid and glucose metabolism through their derived metabolite acetic acid, which is the key target for gut microbe to regulate muscle. Taken together, these results reveal the regulatory mechanism of gut microbes and derived metabolites on muscle metabolism and development, providing a theoretical basis for the healthy regulation of HFD in aquatic animals.

Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear.

We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from Akkermansia muciniphila, and their impact on vasculitis development was assessed.

We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100 also reduced the severity of vascular inflammation.

This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.

Acute pancreatitis (AP) is a prevalent acute gastrointestinal disease, which may be prevented and alleviated by probiotics. Bifidobacterium animalis subsp. lactis BB-12 (BB-12) is a widely studied probiotic strain; however, its specific effects in this context remain unexplored. In this study, we aimed to investigate the prophylactic and therapeutic effects of BB-12 in AP. Our findings revealed that BB-12 administration via gavage significantly reduced pathological pancreatic damage and serum amylase activity. Microbiome analysis showed that BB-12 treatment significantly increased the relative abundance of Ligilactobacillus and decreased that of Bilophila in the gut microbiota of mice with AP. Transcriptome analysis revealed that BB-12 mitigated the AP-induced dysregulation of several pathways, specifically attenuating the upregulation of the pancreatic secretion and ascorbate and aldarate metabolism pathways while reversing the downregulation of the ribosome, oxidative phosphorylation, and thermogenesis pathways. Spearman's correlation analysis revealed a positive correlation between the abundances of Bilophila and ASF356 and serum amylase activity. Furthermore, the abundances of Bilophila and ASF356 were significantly correlated with BB-12-regulated pancreatic genes and were predominantly enriched in the ribosome pathway. In conclusion, BB-12 pretreatment alleviated AP, likely by regulating the abundance of intestinal Lactobacillus, Bilophila, and ASF356, as well as the pancreatic secretion, ascorbate and aldarate metabolism, oxidative phosphorylation, ribosome, and thermogenesis pathways.

5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella, which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter, which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.

Age-related macular degeneration (AMD) is a multifactorial disease, and studies have implicated the role of gut microbiota in its pathogenesis. However, characterization of microbiome dysbiosis and associated microbial-derived metabolomic profiles across AMD stages remains unknown. In this pilot study, we explored how gut microbiome composition and gut-derived metabolites differ in AMD.

Our pilot study analyzed fasted stool samples that were collected from 22 patients at a tertiary academic center. Subjects were classified as control, intermediate AMD, or advanced AMD based on clinical presentation. 16S rRNA amplicon sequencing and standard chromatography-mass spectrometry methods were used to identify bacterial taxonomy composition and abundance of short-chain fatty acids (SCFAs) and bile acids (BAs), respectively. Genetic testing was used to investigate the frequency of 14 high-risk single nucleotide polymorphisms (SNPs) associated with AMD in the AMD cohort.

Forty-three differentially abundant genera were present among the control, intermediate, and advanced groups. Taxa with known roles in immunologic pathways, such as Desulfovibrionales (q = 0.10) and Terrisporobacter (q = 1.16e-03), were in greater abundance in advanced AMD patients compared to intermediate. Advanced AMD patients had decreased abundance of 12 SCFAs, including acetate (P = 0.002), butyrate (P = 0.04), and propionate (P = 0.01), along with 12 BAs, including taurocholic acid (P = 0.02) and tauroursodeoxycholic acid (P = 0.04). Frequencies of high-risk SNPs were not significantly different between the intermediate and advanced AMD groups.

This pilot study identifies distinct gut microbiome compositions and metabolomic profiles associated with AMD and its stages, providing preliminary evidence of a potential link between gut microbiota and AMD pathogenesis. To validate these findings and elucidate the underlying mechanisms, future research with larger cohorts and more comprehensive sampling is strongly recommended.

Diabetes Mellitus (DM) is a metabolic disease that manifests as a state of "chronic low-grade inflammation". Patients with DM have a disorder of intestinal flora. There is a discernible correlation between this disorder of intestinal flora and the onset and progression of eye diseases, which offers novel insights into treating eye diseases through the modulation of intestinal flora. Here, we demonstrated that a high-fat diet and streptozotocin injection-induced intestinal microbiota dysbiosis can lead to dry eye-like manifestations in T2DM mice. Probiotic and prebiotic treatments not only alleviated intestinal inflammation and barrier disruption, but also mitigated damage to the lacrimal barrier and suppressed immune cell infiltration and inflammatory responses. Additional mechanism investigation found that probiotics and prebiotics inhibited the TLR4/NF-κB signaling pathway and its downstream pro-inflammatory products both in the lacrimal gland and colon. 16S RNA sequencing identified a reduction in the bacterial genera Akkermansia and Lactobacillus in the fecal samples of DM mice. By contrast, treatment with probiotics and prebiotics led to a reshaping of the intestinal microbial community and a reduction in bile acid metabolites, such as taurocholic acid and deoxycholic acid. Our current study demonstrates that probiotic and prebiotic treatments can ameliorate dry eye-like symptoms and associated pathological changes in T2DM mice. Moreover, we proved that a high-fat diet and STZ-induced microbiota dysbiosis were involved in diabetic dry eye through the gut-eye axis.

The gut microbiota is firmly associated with the progression of ulcerative colitis (UC). Beneficial microbial metabolites, such as butyrate, exert vital roles in maintaining intestinal homeostasis. The Sea buckthorn berry is a traditional Chinese medicine homologous to food and medicine which is widely applied in the prevention and treatment of UC in clinic practice. Recent studies have exhibited the potential function of Sea buckthorn on regulating the gut microbiota, however, the mechanism underlying its anti-colitis effects and the key gut microbes mediating its efficacy are still unclear.

This study is intended to explore the pharmacological mechanism of the efficacy of Sea buckthorn berries extract (SBE) in alleviating UC from the perspective of the gut microbial regulation.

The effect of SBE on UC was evaluated on dextran sulfate sodium (DSS)-induced murine model by assessing the body weight change, colon length, disease activity index (DAI), histopathological staining and the transcriptional expression of genes associated with inflammation and mucosal integrity. The dependence of the gut microbiota in the therapeutical effects of SBE on UC was confirmed by pseudo-germ-free mice and the co-housing experiment. The differential gut microbes altered by SBE were discovered by 16S rRNA sequencing and qPCR. The levels of short chain fatty acids (SCFAs) in bacterial medium and colonic contents were determined by GC-MS/MS. Bacterial colonization was conducted to estimate the effects of the bacteria on UC and to verify the involvement of the functional bacteria in the efficacy of SBE. A butyrate receptor G protein-coupled receptor (GPR)109A antagonist mepenzolate bromide (MPN) was used to validate the important role of butyrate and GPR109A in the anti-colitis effects of SBE and functional bacteria on UC. Two-way ANOVA was employed for multiple curve comparison and One-way ANOVA and Brown-Forsythe ANOVA test were used for multiple group comparison. Statistical significance was defined as p< 0.05.

SBE treatment significantly alleviated DSS-induced UC and its therapeutical effects was impaired in pseudo-germ-free mice. Moreover, the co-housing experiment exhibited that SBE-altered microbiota could effectively ameliorate UC. Further research demonstrated that Faecalibaculum rodentium was obviously increased by SBE and could be transferable by co-housing. Moreover, butyrate, a product of F. rodentium, dramatically decreased in UC mice while could be recovered by SBE administration. Abolishment of F. rodentium using vancomycin deprived the efficacy of SBE, but this could be reversed by recolonization of F. rodentium. Finally, blockage of the butyrate's receptor GPR109A weakened the effects of F. rodentium, indicating the indispensability of butyrate and GPR109A in the anti-colitis effects of F. rodentium.

SBE has potent therapeutical efficacy on UC including relieving inflammation and enhancing intestinal epithelial integrity, which is mediated by the gut F. rodentium-regulated butyrate-GPR109A axis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of liver disease worldwide, and our understanding of its pathogenesis continues to evolve. MASLD progresses from steatosis to steatohepatitis, fibrosis, and cirrhosis, and this Review explores how the gut microbiome and their metabolites contribute to MASLD pathogenesis. We explore the complexity and importance of the intestinal barrier function and how disruptions of the intestinal barrier and dysbiosis work in concert to promote the onset and progression of MASLD. The Review focuses on specific bacterial, viral, and fungal communities that impact the trajectory of MASLD and how specific metabolites (including ethanol, bile acids, short chain fatty acids, and other metabolites) contribute to disease pathogenesis. Finally, we underscore how knowledge of the interaction between gut microbes and the intestinal barrier may be leveraged for MASLD microbial-based therapeutics. Here, we include a discussion of the therapeutic potential of prebiotics, probiotics, postbiotics, and microbial-derived metabolites.

The gut microbiome and diet are important factors in the pathogenesis and management of Crohn's disease (CD). However, the role of the gut phageome under dietary influences is unknown.

We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection.

We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo.

On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila, which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation.

Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.

The dietary fat supply might interact with the intestinal microbiota via different mechanisms. Research on this topic, however, remains scarce in cats. For this reason, the present study was conducted to evaluate the impact of the fat concentration and fatty acid profile in the diet on the fecal microbiota of healthy cats.

A low-fat basal diet was fed to ten healthy adult cats. The diet was offered without or with the daily addition of 0.5 g or 1 g of sunflower oil, fish oil or lard per kg body weight of the cats, using a randomized cross-over design. Each feeding period lasted for 21 days, and the fecal samples were collected on the last days of each period. The fecal microbiota was analyzed by 16S rDNA sequencing. Additionally, microbial metabolites (short-chain fatty acids, lactate, ammonium, biogenic amines) were measured in the fecal samples.

The dietary treatment had no impact on the alpha-diversity of the fecal microbiota or on the relative abundance of bacterial phyla in the samples. Only a few changes were observed in the relative abundance of bacterial genera and the concentrations of microbial metabolites in the feces, probably being of minor physiological relevance.

The balanced intestinal microbiota of cats seems to be relatively resistant to moderate variations in the dietary fat supply over a short feeding period. Longer-term treatments and higher dietary fat levels should be evaluated in future studies to further clarify the relevance of fat intake for the feline gut microbiome.

Vaccination plays a critical role in public health by reducing the incidence and prevalence of infectious diseases. The efficacy of a vaccine has numerous determinants, which include age, sex, genetics, environment, geographic location, nutritional status, maternal antibodies, and prior exposure to pathogens. However, little is known about the role of gut microbiome in vaccine efficacy and how it can be targeted through dietary interventions to improve immunological responses. Unveiling this link is imperative, particularly in the post-pandemic world, considering impaired COVID-19 vaccine response observed in dysbiotic individuals. Therefore, this article aims to comprehensively review how diet and probiotics can modulate gut microbiome composition, which is linked to vaccine efficacy. Dietary fiber and polyphenolic compounds derived from plant-based foods improve gut microbial diversity and vaccine efficacy by promoting the growth of short-chain fatty acids-producing microbes. On the other hand, animal-based foods have mixed effects - whey protein and fish oil promote gut eubiosis and vaccine efficacy. In contrast, lard and red meat have adverse effects. Studies further indicate that probiotic supplements exert varied effects, mostly strain and dosage-specific. Interlinking diet, microbiome, probiotics, and vaccines will reveal opportunities for newer research on diet-induced microbiome-manipulated precision vaccination strategies against infectious diseases.

Industrialization adversely affects the gut microbiome and predisposes individuals to chronic non-communicable diseases. We tested a microbiome restoration strategy comprising a diet that recapitulated key characteristics of non-industrialized dietary patterns (restore diet) and a bacterium rarely found in industrialized microbiomes (Limosilactobacillus reuteri) in a randomized controlled feeding trial in healthy Canadian adults. The restore diet, despite reducing gut microbiome diversity, enhanced the persistence of L. reuteri strain from rural Papua New Guinea (PB-W1) and redressed several microbiome features altered by industrialization. The diet also beneficially altered microbiota-derived plasma metabolites implicated in the etiology of chronic non-communicable diseases. Considerable cardiometabolic benefits were observed independently of L. reuteri administration, several of which could be accurately predicted by baseline and diet-responsive microbiome features. The findings suggest that a dietary intervention targeted toward restoring the gut microbiome can improve host-microbiome interactions that likely underpin chronic pathologies, which can guide dietary recommendations and the development of therapeutic and nutritional strategies.

Consumption of a high-fat, high-carbohydrate Western-style diet (WD) associated with obesity and inflammation in humans has not been investigated in dogs.

To determine the effects of WD on inflammatory indices, microbiome, and fecal bile acids (BAs) in dogs.

Ten adult clinically healthy dogs.

A dietary trial compared the effects of two home-prepared diets: a high-fiber, low-fat control diet (CD) to a diet containing the macronutrient composition of WD (low-fiber, high fat). Dietary treatments were given sequentially for three feeding periods, each lasting 1 month. Outcome measures included molecular/microbiologic testing of colonic biopsies, histopathology, inflammatory biomarkers, and quantification of fecal BA following each feeding period.

Cell markers of apoptosis (TUNEL-positive cells: CD1, 0.36% ± 0.2%; WD, 0.79% ± 0.5%; CD2, 0.42% ± 0.3%; 95% CI) and inflammation (NF-ĸB area: CD1, 8.09% ± 3.3%; WD, 11.58% ± 3.4%; CD2 7.25% ± 3.8%; 95% CI), as well as serum high-sensitivity C-reactive protein (CD1, 2.0 ± 0.4 ng/mL; WD, 2.76 ± 0.23 ng/mL; CD2, 2.29 ± 0.25 ng/mL; 95% CI), were increased (p < 0.05) in dogs fed WD versus CD. Other perturbations seen with WD ingestion included altered (p < 0.05) colonic mucosal bacteria (bacterial counts: CD1, 301.5 ± 188.5; WD, 769.8 ± 431.9; CD2, 542.1 ± 273.9; 95% CI) and increased (p < 0.05) fecal cholic acid (median and interquartile range/IQR: CD1, 9505 [2384-33 788] peak heights; WD, 34 131 [10 113-175 909] peak heights) and serum myeloperoxidase (CD1, 46.98 ± 16.6 ng/mL; WD, 82.93 ± 33.6 ng/mL; CD2, 63.52 ± 29.5 ng/mL; 95% CI).

WD fed to clinically healthy dogs promotes colonic dysbiosis, altered fecal BA, and low-grade inflammation independent of obesity.

Accumulation of hydrophobic bile acids (BAs) is linked with cancer development. However, derivatives of deoxycholic acid (DCA) and lithocholic acid (LCA) produced via bacterial metabolism may mitigate the proinflammatory and cytotoxic effects of hydrophobic BAs. The impact of diet on secondary BA derivative production has not been determined.

This study aimed to study the associations between BA-modulating nutrients and the composition of secondary BAs and their derivatives.

Stool and blood were collected from 138 participants aged 45-75 y that self-identified as Black or non-Hispanic White. BAs were extracted from stool and serum and quantified using LC/ESI-MS/MS. Energy, macronutrients, micronutrients, and specific dietary nutrients were estimated from two 24-h diet recalls. The abundance of genes for microbial BA metabolism was assessed from stool metagenomes. Kendall τ correlation and regression-based modeling were performed to determine associations between BA categories, microbial genes, and select energy-adjusted dietary variables (alcohol, calcium, coffee, fiber, fat, and protein).

Participants had a mean age of 60 y and a mean BMI of 31 kg/m2. BA derivatives were present in all participant stools, with lagodeoxycholic acid being the most abundant derivative quantified. Analysis of stool microbial metagenomes revealed the presence of genes for secondary BA derivative production in all participants. Protein is positively associated with the accumulation of secondary BAs. monounsaturated fatty acids (MUFA)s were negatively associated with high abundant derivatives of DCA in regression models. Total fiber and coffee intake were positively correlated with increased conversion of BAs to derivatives. Race and smoking status were significant predictors of associations between dietary variables and BA derivatives.

Protein, MUFAs, total fiber and coffee are significantly associated with concentrations of secondary BAs and their derivatives. Future work should account for social and structural influences on dietary intake and its relationship with BA-elicited cancer risk.

The gut microbiota plays a pivotal role in influencing the metabolism and immune responses of the body. A balanced microbial composition promotes metabolic health through various mechanisms, including the production of beneficial metabolites, which help regulate inflammation and support immune functions. In contrast, imbalance in the gut microbiota, known as dysbiosis, can disrupt metabolic processes and increase the risk of developing diseases, such as obesity, type 2 diabetes, and inflammatory disorders. The composition of the gut microbiota is dynamic and can be influenced by environmental factors such as diet, medication, and the consumption of live bacteria. Since the early 1900s, bacteria isolated from food and have been used as probiotics. However, the human gut also offers an enormous reservoir of bacterial strains, and recent advances in microbiota research have led to the discovery of strains with probiotic potentials. These strains, derived from a broad spectrum of microbial taxa, differ in their ecological properties and how they interact with their hosts. For most probiotics bacterial structural components and metabolites, such as short-chain fatty acids, contribute to the maintenance of metabolic and immunological homeostasis by regulating inflammation and reinforcing gut barrier integrity. Metabolites produced by probiotic strains can also be used for bacterial cross-feeding to promote a balanced microbiota. Despite the challenges related to safety, stability, and strain-specific properties, several newly identified strains offer great potential for personalized probiotic interventions, allowing for targeted health strategies.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), result from a loss of immune tolerance to gut microbiota, leading to inflammation. Their incidence is increasing, especially in newly industrialized countries. The etiology is multifactorial, involving genetic, immune, microbiota, and environmental factors. Maternal microbiome changes during pregnancy can elevate IBD risk in offspring, influenced by diet, smoking, and antibiotic exposure. Early life microbiota manipulation shows promise for preventing IBD. Epidemiological and pre-clinical studies highlight diet's significant role in IBD development. High-inflammatory dietary patterns correlate with increased CD risk, while Mediterranean-like diets promote beneficial gut microbiome changes and reduce inflammation. Certain food additives, such as emulsifiers and artificial sweeteners, may exacerbate IBD by altering gut microbiota. A systematic review indicates that higher ultra-processed food consumption significantly increases CD risk. Lifestyle modifications, including healthy dietary adherence, could substantially reduce IBD risk, with studies showing that favorable choices can halve the risk in genetically predisposed individuals. Additionally, maternal diet impacts offspring IBD risk, as seen in mouse models where high-fat diets led to increased inflammation. Evidence suggests that maternal probiotics and specific dietary patterns may mitigate these risks. Overall, these findings emphasize the potential for dietary interventions to modulate gut microbiota and immune responses, offering promising avenues for IBD prevention and management. Further large-scale studies are needed to explore the impact of dietary strategies on IBD risk and gut health.