Microbiota transplant therapy is an emerging therapy for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor factors (such as age and patient relationship), recipient factors, control selection, and elements impacting engraftment and its correlation with clinical response. We also examine potential mechanisms through inflammatory bowel disease trials, focusing on the interplay between the microbiota, host, and immune system. Finally, we briefly explore potential future directions for microbiota transplant therapy and promising emerging treatments.

The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.

Gut bacteria play key roles in intestinal physiology, via the secretion of diversified bacterial effectors. Many of these effectors remodel the host proteome, either by altering transcription or by regulating protein post-translational modifications. SUMOylation, a ubiquitin-like post-translational modification playing key roles in intestinal physiology, is a target of gut bacteria. Mutualistic gut bacteria can promote SUMOylation, via the production of short- or branched-chain fatty acids (SCFA/BCFA). In contrast, several pathogenic bacteria were shown to dampen SUMOylation in order to promote infection. Here, we demonstrate that Staphylococcus warneri, a natural member of the human gut microbiota, decreases SUMOylation in intestinal cells. We identify that Warnericin RK, a hemolytic toxin secreted by S. warneri, targets key components of the host SUMOylation machinery, leading to the loss of SUMO-conjugated proteins. We further demonstrate that Warnericin RK promotes inflammation in intestinal and immune cells using both SUMO-dependent and SUMO-independent mechanisms. We finally show that Warnericin RK regulates the expression of genes involved in intestinal tight junctions. Together, these results highlight the diversity of mechanisms used by bacteria from the gut microbiota to manipulate host SUMOylation. They further highlight that changes in gut microbiota composition may impact intestinal inflammation, by altering the equilibrium between bacterial effectors promoting or dampening SUMOylation.

Parkinson's disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing α-synuclein protein. In recent decades, however, accumulating research has revealed that Parkinson's disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut, called the "gut-brain axis." Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson's disease patients, with findings including impaired intestinal permeability, heightened inflammation, and distinct gut microbiome profiles and metabolites. Furthermore, α-synuclein deposition has been consistently observed in the gut of Parkinson's disease patients, suggesting a potential role in disease initiation. Importantly, individuals with vagotomy have a reduced Parkinson's disease risk. From these observations, researchers have hypothesized that α-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut-brain axis, leading to Parkinson's disease. This review comprehensively examines the gut's involvement in Parkinson's disease, focusing on the concept of a gut-origin for the disease. We also examine the interplay between altered gut-related factors and the accumulation of pathological α-synuclein in the gut of Parkinson's disease patients. Given the accessibility of the gut to both dietary and pharmacological interventions, targeting gut-localized α-synuclein represents a promising avenue for developing effective Parkinson's disease therapies.

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.

Roseburia intestinalis is one of the most abundant and important butyrate-producing human gut anaerobic bacteria that plays an important role in maintaining health and is a potential next-generation probiotic. We investigated the pangenome of 16 distinct strains, isolated over several decades, identifying local and time-specific adaptations. More than 50% of the genes in each individual strain were assigned to the core genome, and 77% of the cloud genes were unique to individual strains, revealing the high level of genome conservation. Co-carriage of the same enzymes involved in carbohydrate binding and degradation in all strains highlighted major pathways in carbohydrate utilization and reveal the importance of xylan, starch and mannose as key growth substrates. A single strain had adapted to use rhamnose as a sole growth substrate, the first time this has been reported. The ubiquitous presence of motility and sporulation gene clusters demonstrates the importance of these phenotypes for gut survival and acquisition of this bacterium. More than half the strains contained functional, potentially transferable, tetracycline resistance genes. This study advances our understanding of the importance of R. intestinalis within the gut ecosystem by elucidating conserved metabolic characteristics among different strains, isolated from different locations. This information will help to devise dietary strategies to increase the abundance of this species providing health benefits.

The enteric microbiota is an established reservoir for multidrug-resistant organisms that present urgent clinical and public health threats. Observational data and small interventional studies suggest that microbiome interventions, such as fecal microbiota products and characterized live biotherapeutic bacterial strains, could be an effective antibiotic-sparing prevention approach to address these threats. However, bacterial colonization is a complex ecological phenomenon that remains understudied in the context of the human gut. Antibiotic resistance is one among many adaptative strategies that impact long-term colonization. Here we review and synthesize evidence of how bacterial competition and differential fitness in the context of the gut present opportunities to improve mechanistic understanding of colonization resistance, therapeutic development, patient care, and ultimately public health.

Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut-brain axis, gut-liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent disorder of excessive fat accumulation and inflammation in the liver that currently lacks effective therapeutic interventions. Fu brick tea (FBT) has been shown to ameliorate liver damage and modulate gut microbiota dysbiosis in NAFLD, but the potential mechanisms have not been comprehensively elucidated, especailly whether its hepatoprotective effects are determined to depend on the homeostasis of gut microbiota, intestinal barrier function and hepatic immune microenvironment. In this study, our results further demonstrated that FBT not only alleviated NAFLD symptoms and related endotoxemia in high-fat diet (HFD)-fed rats, but also attenuated intestinal barrier dysfunction and associated inflammation, also confirmed in Caco-2 cell experiment. Meanwhile, FBT intervention significantly relieved HFD-induced gut microbiota dysbiosis, characterized by increased diversity and composition, particularly facilitating beneficial microbes, including short chain fatty acids (SCFAs) and bile acids producers, such as Blautia and Fusicatenibacter, and inhibiting Gram-negative bacteria, such as Prevotella_9 and Phascolarctobacterium. Also, the gut microbiota-dependent hepatoprotective effects of FBT were verified by fecal microbiota transplantation (FMT) experiment. Thus, the beneficial moulation of gut microbiota altered by FBT in levels of SCFAs, bile acids and lipopolysaccharides, intestinal barrier function and TLR4/NF-κB pathway contributed to alleviate liver steatosis and inflammation. Additionally, the hepatoprotective effects of FBT was further demonstrated by suppressing Kupffer cell activation and regulating lipid metabolism using an ex vivo model of liver organoid. Therefore, FBT supplementation can maintain intenstinal homeostasis and remodel hepatic immune microenvironment to prevent NAFLD and associated endotoxemia.

Parkinson's disease (PD) is characterized by the aggregation of α-synuclein (α-syn) and the loss of dopaminergic (DA) neurons, with growing evidence suggesting a significant role of gut microbiota and their metabolites in the disease's pathogenesis. This study explores the effects of short-chain fatty acids (SCFAs) on PD progression, focusing on the G protein-coupled receptor 43 (GPR43) and the NLRP3 signaling pathway in both in vitro and in vivo models. Employing the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model and SH-SY5Y cells with SCFAs-treated, this study investigated the impact of SCFAs on α-syn deposition, DA loss, and neuroinflammation. In vitro, supernatant from STC-1 cells was administered to SH-SY5Y cells, and the effects were assessed following the knockdown of NLRP3 or GPR43. In vivo, mice were treated with NLRP3 or GPR43 inhibitors after feeding with SCFAs, and the motor deficits, α-syn pathology, DA neuronal loss, and inflammatory responses were observed. SCFAs were found to exacerbate motor and gastrointestinal dysfunctions in PD models, intensifying α-syn pathology and neuroinflammation. The activation of the NLRP3 inflammasome through GPR43 emerged as a key pathological mechanism, with inhibition of these molecules mitigating the observed effects. Such interventions reduced α-syn accumulation, DA loss, and inflammatory responses, highlighting the pivotal role of the SCFA/GPR43-NLRP3 pathway in PD. The findings from this study elucidate a critical link between gut-derived metabolic changes and neuroinflammatory processes in PD via the SCFA/GPR43-NLRP3 pathway. Targeting this pathway offers a promising therapeutic strategy and enriches our understanding of the gut-brain axis' role in PD progression.

The influence of gut microbiota on Type 2 Diabetes Mellitus (T2DM) is an emerging area of research. This review investigates the relationship between gut microbiota dysbiosis, bacterial translocation, and T2DM. It aims to elucidate how microbial imbalances contribute to the progression of T2DM through bacterial translocation and to evaluate dietary and therapeutic strategies to manage these effects.

Recent studies highlight that dysbiosis in T2DM patients often leads to increased systemic inflammation, impaired glucose metabolism, and disrupted gut barrier integrity. These disruptions promote elevated levels of harmful bacterial components, such as lipopolysaccharides, in the bloodstream. This, in turn, is linked to worsening insulin resistance and metabolic dysfunction. Advances in molecular methods and biomarkers have provided deeper insights into bacterial translocation and its impact on diabetes. Dietary interventions, including nutraceutical agents, high-fiber and low-glycemic index diets, as well as the use of probiotics and prebiotics, have shown promise in restoring gut health and mitigating bacterial translocation.

Maintaining a balanced gut microbiota and intestinal barrier integrity is crucial for managing T2DM. Therapeutic strategies, including dietary modifications and nutraceuticals, have demonstrated potential in reducing bacterial translocation and systemic inflammation. Continued research is needed to refine these approaches and explore novel treatment modalities for improving metabolic health in T2DM patients.

Podophyllotoxin (PPT), an extract from the traditional medicinal plant Dysosma, offers anti-viral and anti-cancer benefits, though its use is limited by toxicity. The mechanisms of PPT's inherent pulmonary toxicity remain elusive. This study leverages the novel "Toxicological Evidence Chain" theory to explore the potential involvement of the "gut-lung axis" in PPT-induced pulmonary toxicity. In this study, we examined injury phenotypes in rats, evaluated pulmonary pathological changes, measured pro-inflammatory factors, and conducted comprehensive analyses of both pulmonary and gut microbiomes and metabolomics. Our findings indicate that exposure to PPT leads to significant pulmonary damage in these animals. The PPT group exhibited significantly elevated levels of total protein, albumin, alkaline phosphatase, and lactate dehydrogenase in bronchoalveolar lavage fluid, accompanied by marked upregulation of interleukin (IL)-18, tumor necrosis factor-alpha, IL-6, and IL-1β expression in lung tissue. Furthermore, 16S rRNA gene sequencing analysis revealed significant increases of Akkermansia, Escherichia-Shigella, and Bacteroides in both intestinal contents and lung tissue of PPT-treated animals, concomitant with notable elevations in short-chain fatty acids (SCFAs) such as isobutyric acid and isovaleric acid, and reductions in acetic acid, propionic acid, and butyric acid. The increased abundance of Akkermansia and Escherichia-Shigella may enhance pulmonary inflammatory factors through effects on intestinal barrier integrity and direct immune stimulation, while elevated Bacteroides may alter SCFA production, exacerbating pulmonary inflammation under PPT treatment, suggesting a potential role in the manifestation of PPT-induced pulmonary toxicity. This study offers new insights into the mechanisms of PPT-induced pulmonary toxicity, highlights the role of the gut-lung axis, and provides avenues for therapeutic intervention.

PPT, derived from the medicinal plant Dysosma, is known for its anti-cancer and anti-viral properties but limited by severe pulmonary toxicity. This study illuminates the gut-lung microbiota axis's role in mediating this toxicity, revealing how specific microbial and metabolic alterations contribute to lung damage. By uncovering these mechanisms, our research opens avenues for interventions that could mitigate PPT's side effects, potentially enhancing its safety and widening its therapeutic use.

Prior studies have indicated a notable link between gut health and metabolic syndrome (MetS). The cardiometabolic index (CMI), an innovative indicator of metabolic health, effectively predicts MetS. Bowel movement frequency (BMF) closely reflects gastrointestinal function and is a key sign of gut health. Nonetheless, the relationship between CMI and BMF is still unclear. Our research explores the possible association between these two variables.

This study employed 2005 to 2010 National Health and Nutrition Examination Survey data. The CMI for each participant was determined by triglycerides, high-density lipoprotein cholesterol, and the waist-to-hip ratio. Multiple regression, smooth curve fitting, and threshold effect analyses were employed to investigate the association between CMI and BMF. The association's stability across populations was assessed through subgroup analyses and interaction tests.

The study included 9,678 participants in total. After controlling for potential confounding variables, those in the uppermost CMI quartile had a 0.69 more increase in BMF than the bottom quartile (β = 0.69, 95% CI: 0.34, 1.03). The trend analyses showed that BMF increased steadily with the advancement of the CMI quartiles (P for trend < 0.0001). Associations between CMI and BMF were shown to be nonlinear through smooth curve fitting and threshold effect analyses. Specifically, when CMI ranged from 4.97 to 11.75, a negative connection was observed (β = -0.78, 95% CI: -1.33, -0.23), while positive associations were identified in other ranges. Subgroup analyses and interaction tests indicated significant CMI and BMF association variations when stratified by depression and age categories (P for interaction < 0.05).

This research indicates that CMI is generally associated with an increase in BMF. However, when CMI ranges from 4.97 to 11.75, it is associated with a BMF decrease. Notably, the association of CMI and BMF is more potent in young, middle-aged, and depressed people.

Alterations in the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Chlorogenic acid (CGA), a product of the esterification of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and has potential beneficial effects on gut function. However, the underlying mechanisms remain unclear. In this study, the pharmacological effects of CGA on colitis and the potential underlying mechanisms were investigated.

A mouse model of colitis was induced via the use of 4 % dextran sulfate sodium (DSS), and the mice were treated with 200 mg/kg CGA. Body weight, colon length, colon tissue pathology, and plasma and colon inflammatory cytokine levels were assessed. RNA sequencing was used to detect changes in gene expression in mouse colon tissues, and 16S rRNA sequencing was used to analyze the composition and structure of the gut microbiota. Fecal metabolomic analysis was performed, and fecal microbiota transplantation (FMT) was used to evaluate the contribution of the gut microbiota.

CGA significantly alleviated DSS-induced colitis, alleviating intestinal mucosal barrier damage and gut microbiota dysbiosis. It significantly enriched bacteria that produce short-chain fatty acids (SCFAs). CGA inhibited the accumulation of purine metabolites derived from the microbiota and suppressed immune-related signaling cascades, exerting immunomodulatory effects. Furthermore, the gut microbiota of CGA-treated mice alleviated DSS-induced colitis through FMT.

CGA alleviates colitis in a gut microbiota-dependent manner, potentially providing a new strategy for the treatment of IBD.

This review discusses the epidemiology, pathophysiology, and factors associated with refractory immune-mediated diarrhea and colitis (r-IMDC), emphasizing tailored treatment strategies.

The current literature on r-IMDC was reviewed using PubMed (2015-2025), focusing on clinical trials, meta-analyses, and case reports relevant to its management.

Effectively managing r-IMDC is crucial for balancing toxicities and antitumor response. Available second and third-line management options for r-IMDC cases must be carefully evaluated. Future perspectives include development of standardized protocols beyond second-line therapies and predictive biomarkers to enable personalized treatment.

Colorectal cancer (CRC) development is influenced by both iron and gut microbiota composition. While iron supplementation is routinely used to manage anemia in CRC patients, it may also impact gut microbiota and promote tumorigenesis. In this study, we investigated the impact of initial gut microbiota composition on iron-promoted tumorigenesis. We performed fecal microbiota transplantation (FMT) in ApcMin/+ mice using samples from healthy controls, CRC patients, and mice, followed by exposure to iron sufficient or iron excess diets.

We found that iron supplementation promoted CRC and resulted in distinct gut microbiota changes in ApcMin/+ mice receiving FMT from CRC patients (FMT-CRC), but not from healthy controls or mice. Oral treatment with identified bacterial strains, namely Faecalibaculum rodentium, Holdemanella biformis, Bifidobacterium pseudolongum, and Alistipes inops, protected FMT-CRC mice against iron-promoted tumorigenesis.

Our findings suggest that microbiota-targeted interventions may mitigate tumorigenic effects of iron supplementation in anemic patients with CRC.

Natural polysaccharides, a class of biological macromolecules found in nature, have recently attracted considerable interest owing to their notable anti-aging capabilities. This article provides a comprehensive review of the intricate mechanisms through which natural polysaccharides combat aging, as well as their applications in addressing skin aging. Primarily, these polysaccharides manifest their anti-aging effects via diverse pathways, such as antioxidation, gut microbiota regulation, metabolic modulation, and immune system regulation. The anti-aging efficacy of natural polysaccharides is intrinsically linked to their structure-activity relationships, with critical determinants including molecular weight, monosaccharide composition, and chemical architecture. Polysaccharides with lower molecular weights typically demonstrate enhanced biological activity, whereas specific monosaccharide configurations and chemical modifications can markedly augment their anti-aging potential. The utilization of natural polysaccharides in skin aging holds significant promise, offering benefits such as anti-aging, wrinkle reduction, anti-glycation, and the facilitation of skin regeneration. In conclusion, this article synthesizes the advancements in research on natural polysaccharides within the anti-aging sector and forecasts future trajectories, to establish a robust foundation for the innovation of new polysaccharide-derived anti-aging formulations.

Acne pathogenesis is multifactorial, involving systemic factors including gut dysbiosis, hormones, and chronic inflammation. Probiotics, myoinositol, and plant-derived molecules may modulate acne by targeting these factors. The objective is to compare a synbiotic containing herbs against a myoinositol-based herbal supplement on how they influence acne, the gut microbiome, short chain fatty acids (SCFAs), and hormonal profiles.

This was an 8-week, randomized study involving 36 male and female patients aged 12 to 45 years with non-cystic acne. Subjects received either a synbiotic or a myoinositol-based herbal supplement (MBHS). Acne lesions were counted, stool samples were collected for gut microbiome and SCFA analyses, and hormone collections were performed at baseline, 4, and 8 weeks.

Several gut bacteria increased by at least threefold at both week 4 and 8 in the synbiotic (Erysipelatoclostridium merdavium, Blautia argi, Faecalibacterium prausnitzii, Prevotella copri, Streptococcus sp001556435, Blautia sp900541955) and MBHS group (Megamonas funiformis, Ligilactobacillus ruminis, Prevotella ssp015074785, Prevotella copri, Gca-900199835 sp900176495). Acne lesion counts decreased significantly in both groups at week 4 (p < 0.0001) and week 8 (synbiotic, p < 0.0001; MBHS, p < 0.0001). There were significant and trending increases in stool and plasma SCFAs in both cohorts at week 4 and 8. After 8 weeks of MBHS, 17-OHP and androstenedione significantly decreased from 27.3 to 11.3 pg/ml (p = 0.001) and 94.9 to 68.0 pg/ml (p = 0.04), respectively.

Both the synbiotic and MBHS improved gut health, augmented SCFAs, and reduced lesion counts in those with non-cystic acne. The MBHS may act by reducing hormone levels of 17-OHP and androstenedione.

www.

gov (NCT05919810).

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

The relationship between alterations in brain microstructure and dysbiosis of gut microbiota in Alzheimer's disease (AD) has garnered increasing attention, although the functional implications of these changes are not yet fully elucidated. This research examines how neuroinflammation, systemic inflammation, and gut microbiota interact in male 3 × Tg-AD and B6129SF1/J wild-type (WT) mice at 6 months-old (6-MO) and 12 months-old (12-MO). Employing a combination of behavioral assessments, diffusion kurtosis imaging (DKI), microbiota profiling, cytokine analysis, short-chain fatty acids (SCFAs), and immunohistochemistry, we explored the progression of AD-related pathology. Significant memory impairments in AD mice at both assessed ages were correlated with altered DKI parameters that suggest neuroinflammation and microstructural damage. We observed elevated levels of pro-inflammatory cytokines, such as IL-1β, IL-6, TNFα, and IFN-γ, in the serum, which were associated with increased activity of microglia and astrocytes in brain regions critical for memory. Although gut microbiota analysis did not reveal significant changes in alpha diversity, it did show notable differences in beta diversity and a diminished Firmicutes/Bacteroidetes (F/B) ratio in AD mice at 12-MO. Furthermore, a reduction in six kinds of SCFAs were identified at two time points of 6-MO and 12-MO, indicating widespread disruption in gut microbial metabolism. These findings underscore a complex bidirectional relationship between systemic inflammation and gut dysbiosis in AD, highlighting the gut-brain axis as a crucial factor in disease progression. This study emphasizes the potential of integrating DKI metrics, microbiota profiling, and SCFA analysis to enhance our understanding of AD pathology and to identify new therapeutic targets.

The gut biome, a complex ecosystem of micro- and macro-organisms, plays a crucial role in human health. A disruption in this evolutive balance, particularly during early life, can lead to immune dysregulation and inflammatory disorders. 'Biome repletion' has emerged as a potential therapeutic approach, introducing live microbes or helminth-derived products to restore immune balance. While helminth therapy has shown some promise, significant challenges remain in optimizing clinical trials. Factors such as patient genetics, disease status, helminth species, and the optimal timing and dosage of their products or metabolites must be carefully considered to train the immune system effectively. We aim to discuss how helminths and their products induce trained immunity as prospective to treat inflammatory and autoimmune diseases. The molecular repertoire of helminth excretory/secretory products (ESPs), which includes proteins, peptides, lipids, and RNA-carrying extracellular vesicles (EVs), underscores their potential to modulate innate immune cells and hematopoietic stem cell precursors. Mimicking natural delivery mechanisms like synthetic exosomes could revolutionize EV-based therapies and optimizing production and delivery of ESP will be crucial for their translation into clinical applications. By deciphering and harnessing helminth-derived products' diverse modes of action, we can unleash their full therapeutic potential and pave the way for innovative treatments.

The study of bacterial metabolism holds immense significance for improving human health and advancing agricultural practices. The prospective applications of genomically encoded bacterial metabolism present a compelling opportunity, particularly in the light of the rapid expansion of genomic sequencing data. Current metabolic inference tools face challenges in scaling with large datasets, leading to increased computational demands, and often exhibit limited inter-relatability and interoperability. Here, we introduce the Integrated Biosynthetic Inference Suite (IBIS), which employs deep learning models and a knowledge graph to facilitate rapid, scalable bacterial metabolic inference. This system leverages a series of Transformer based models to generate high quality, meaningful embeddings for individual enzymes, biosynthetic domains, and metabolic pathways. These embedded representations enable rapid, large-scale comparisons of metabolic proteins and pathways, surpassing the capabilities of conventional methodologies. The examination of evolutionary and functionally conserved metabolites across diverse bacterial species is facilitated by integrating the predictive capabilities of IBIS into a graph database enriched with comprehensive metadata. The consideration of both primary and specialized metabolism, combined with an embedding logic for enzyme discovery, uniquely positions IBIS to identify potential novel metabolic pathways. With the expansion of genomic data necessitating transformative approaches to advance molecular metabolism research, IBIS delivers an AI-driven holistic investigation of bacterial metabolism.

The gut serves not only as digestive but also as critical immune organ, playing a vital role in maintaining the growth performance and immune function of poultry. Atractylodes macrocephala Koidz (AMK) is known for its antioxidant, anti-inflammatory and immunomodulatory properties. This study utilized a Cyclophosphamide (CTX)-induced gut injury model to explore the effects of Polysaccharide of Atractylodes macrocephala Koidz (PAMK) and the Jiawei Si-jun-zi Decoction (JSD) on alleviating gut injury and modulating immune function. The experimental results demonstrated that CTX significantly reduced the average daily gain (ADG) and antioxidant capacity of broiler chicks, disrupted intestinal barrier function, and induced gut microbiota dysbiosis. However, supplementation with PAMK and JSD significantly improved ADG, enhanced antioxidant enzyme activity, alleviated oxidative stress, and upregulated the expression of barrier-related genes such as ZO-1 and Occludin. Additionally, PAMK and JSD significantly increased anti-inflammatory cytokines, including IL-10 and TGF-β, improved gut microbiota diversity, enriched beneficial microbial populations, and restored the microbiota balance disrupted by CTX. These findings suggest that PAMK and JSD effectively mitigate CTX-induced intestinal injury by regulating the antioxidant system, strengthening intestinal barrier function, and restoring gut microbiota structure. This study provides a scientific basis for the development of safe and effective feed additives and proposes a novel strategy to reduce antibiotic use in poultry farming.

Punicic acid (PA) is a chief component of pomegranate seed oil with several health benefits. In this study, the in vitro immunomodulatory activity of PA was assessed using RAW264.7 cells, revealing that PA activated the macrophages, facilitated the concentration of immune-related cytokines and enzymes, and regulated the immune-related NF-κB and MAPK signaling pathways. Further, the in vivo immune-enhancing effect of PA was evaluated with the cyclophosphamide (CTX)-induced immune-compromised mouse model with 16S rDNA amplicon sequencing and relative quantification of lipidome. Results indicated that high doses of PA (200 mg kg-1) remarkably restored CTX-induced immune injury by enhancing the innate and adaptive immunity to stimulate the secretion of immune-related factors. In addition, PA improved gut microbiota dysbiosis and ameliorated lipid metabolism disorders. Our research provides a theoretical basis for the exploitation of PA as a functional component with immune-enhancing effects and adds to the potential health uses of pomegranate seed oil.

Butyrate-producing Clostridium spp. play fundamental roles in maintaining gut microbiota homeostasis by producing short-chain fatty acids. However, exploration of the strain resources and their probiotic effects remains limited. In previous work, a novel species of butyrate-producing Clostridium, Clostridium cellabutyricum YQ-FP-027T, was isolated from the pit mud of Chinese Baijiu brewing, which possesses antibacterial activities by modulating gut microbiota. The present study investigated the probiotic effects of YQ-FP-027T on mice with dextran sulfate sodium (DSS)-induced colitis and the underlying mechanism. The results showed that the mice treated with YQ-FP-027T exhibited lower disease activity index (DAI), recovered weight loss, and reduced colon shortening. Regarding gut microbial composition, these mice showed increased Shannon and Species richness observed (Sobs) indexes and a rising abundance of beneficial bacteria such as Akkermansia and Alistipes. Additionally, the expression levels of inflammatory factors Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) were suppressed, while those of anti-inflammatory factor Interleukin-10 (IL-10) and the cathelicidin-related antimicrobial peptide (CRAMP) were enhanced under YQ-FP-027T treatment. These results suggest that YQ-FP-027T holds potential as a promising probiotic against DSS-induced colitis via optimizing gut microbial community structure and modulating gut immune microenvironment.

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.

Defects in SLC26A3, the major colonic Cl-/HCO3- exchanger, result in chloride-rich diarrhea, a reduction in short-chain fatty acid (SCFA)-producing bacteria, and a high incidence of inflammatory bowel disease in humans and in mice. Slc26a3-/- mice are, therefore, an interesting animal model for spontaneous but mild colonic inflammation and for testing strategies to reverse or prevent the inflammation. This study investigates the effect of Escherichia coli Nissle (EcN) application on the microbiome, SCFA production, barrier integrity, and mucosal inflammation in slc26a3-/- mice.

In vivo fluid absorption and bicarbonate secretion were assessed in the gut of slc26a3+/+ and slc26a3-/- mice before and during luminal perfusion with 100 mM sodium acetate. Age-matched slc26a3+/+ and slc26a3-/- mice were intragastrically gavaged twice daily with 2 × 108 CFU/100 µL of EcN for 21 days. Body weight and stool water content were assessed daily, and stool and tissues were collected for further analysis.

Addition of sodium acetate to the lumen of the proximal colon significantly increased fluid absorption and luminal alkalinization in the slc26a3-/- mice. Gavage with EcN resulted in a significant increase in SCFA levels and the expression of SCFA transporters in the slc26a3-/- cecum, the predominant habitat of EcN in mice. This was accompanied by an increase in mucus-producing goblet cells and a decrease in the expression of inflammatory markers as well as host defense antimicrobial peptides. EcN did not improve the overall diversity of the luminal microbiome but resulted in a significant increase in SCFA producers Lachnospiraceae and Ruminococcaceae in the slc26a3-/- feces.

These findings suggest that EcN is able to proliferate in the inflamed cecum, resulting in increased microbial SCFA production, decreased inflammation, and improved gut barrier properties. In sufficient dosage, probiotics may thus be an effective anti-inflammatory strategy in the diseased gut.

The intestinal microbiota is a key environmental factor in the development of colorectal cancer (CRC). Here, we report that, in the context of mild colonic inflammation, the microbiota protects against colorectal tumorigenesis in mice. This protection is achieved by microbial suppression of the long non-coding RNA (lncRNA) Snhg9. Snhg9 promotes tumor growth through inhibition of the tumor suppressor p53. Snhg9 suppresses p53 activity by dissociating the p53 deacetylase sirtuin 1 (SIRT1) from the cell cycle and apoptosis regulator 2 (CCAR2). Consequently, the depletion of the microbiota by antibiotics causes upregulation of Snhg9 and accelerates CRC progression. Moreover, Snhg9 is functionally conserved. Human SNHG9 promotes tumor growth via the same mechanism as mouse Snhg9, despite their low sequence similarity.

Magnolia officinalis is a medicinal herb known for its pharmacological properties and as a potential natural feed additive. We aimed to assess the effects of dietary Magnolia officinalis extract (MOE) on the growth performance and immune function of piglets, and explored the potential of MOE as a natural alternative to antibiotics for piglet nutrition during weaning.

Compared with the basal diet group (CK), the MOE diet significantly increased average daily feed intake and reduced diarrhea incidence and serum interleukin-6 (IL-6) levels. Compared with 0.1% MOE group, the 0.05% MOE group had lower diarrhea rates, eosinophils (EOS) count, EOS' percentage, and serum interleukin-4 levels. Compared with CK, 0.05% MOE supplementation in the diet could reduce the diarrhea incidence and the thymus index by elevating the levels of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) in the serum, jejunum, and ileum. Compared with the basal diet group, 0.05% MOE supplementation upregulated the mRNA expressions of IL-10 and TGF-β1 in the jejunum and ileum (P < 0.05) and those of IL-10, interleukin-1β (IL-1β), and interferon-γ (IFN-γ) in the thymus (P < 0.05). Moreover, 0.05% MOE increased the levels of butyric, isobutyric, isovaleric, and valeric acids in the colon.

MOE supplementation could modulate the immune status of animals, lower production costs, and contribute to more sustainable and ethical pig farming practices by promoting healthier growth and reducing disease susceptibility. Our findings offer a sustainable solution to antibiotic use in animal farming, addressing concerns about antibiotic resistance and food safety.

Dyslipidemia is a major risk factor for cardiovascular diseases and is influenced by genetic and environmental factors, including diet. Emerging research suggests a link between the gut microbiome and metabolic disorders. While the connection between the gut microbiota and dyslipidemia is well documented, the specific relationship between oral bacteria and dyslipidemia has not been thoroughly investigated. This study aimed to identify oral bacterial species associated with dyslipidemia in a community-based Japanese population. We conducted a metagenomic analysis on tongue coating samples from 763 participants in the Iwaki Health Promotion Project, which were collected during health checkups in 2017 and 2019. Dyslipidemia was diagnosed using standard lipid level criteria. The oral microbiome was analyzed via 16S rDNA amplicon sequencing. Statistical analyses included multiple regression and β diversity assessments. Our analysis revealed that the abundances of several bacterial genera, including Veillonella, Atopobium, Stomatobaculum, Tanneralla, and Megasphaera, are significantly associated with dyslipidemia. A higher relative abundance of Megasphaera was specifically observed in individuals with dyslipidemia. Moreover, Megasphaera abundance was closely associated with the onset of dyslipidemia (P = 0.038, odds ratio: 1.005, 95% confidence interval: 1.000-1.009), suggesting its role in metabolic regulation. This study revealed a significant association between the abundance of specific oral bacteria and dyslipidemia, suggesting the potential of using the oral microbiota as a biomarker for the early detection and management of dyslipidemia. Future research should explore the mechanisms through which oral bacteria influence lipid metabolism and the potential for microbioma-based therapies.

Human papillomavirus (HPV) is a sexually transmitted virus, whose persistent infection is the main reason for invasive cervical cancer (ICC), which is the fourth most common type of cancer in women, with more than 500 000 new cases every year. After infection, various alterations occur in the host, facilitating the virus's evasion of immune system clearance and promoting its proliferation. Oral probiotic consumption can influence the whole body's immunity, inflammatory reflection, neural, endocrine humoral, metabolic pathways and other organs by adjusting the components of gut microbiota (GM). Some evidence shows there is a tight connection between GM and vaginal microbiota (VM), which is referred to as the gut-vaginal axis. This review investigates the potential role of probiotics in clearing HPV via the gut-vagina axis, emphasizing the effectiveness of Lactobacillus in preventing vaginal diseases and suggesting its potential for HPV clearance. Understanding the role of probiotics in the gut-vagina axis could pave the way for new strategies to reduce and eliminate HPV and related diseases.

Type 2 diabetes mellitus (T2DM), a widespread chronic metabolic disorder, presents a global challenge. Metformin hydrochloride, although widely prescribed, is associated with notable side effects. This study aims to explore safer, more effective alternatives by assessing the impact of Ruditapes philippinarum polysaccharides (RPPs) on glycemic control and modulation of microbiota in T2DM mice. A T2DM mouse model was established through a high-sucrose/high-fat diet and intraperitioneal streptozotocin injection. Glycometabolism indicators, histopathological features, and gut microbiota composition in caecum samples were assessed. Following 4 weeks of RPPs intervention, fasting blood glucose (FBG), glycated serum protein (GSP), area under the curve (AUC) of oral glucose tolerance test (OGTT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) levels were reduced in T2DM mice, while AKT-1 and GLUT-2 transcription levels were significant increased. Short-chain fatty acids (SCFAs) concentrations notably increased in the RPP-L group compared to the Model group, with improvements also observed in medium-chain fatty acids (MCFAs) and secondary bile acids (SBAs). Regarding gut microbiota, the Firmicutes-to-Bacteroidetes (F/B) ratio in RPP-L was substantially lower than in the Model group. At the genus level, beneficial bacteria, such as Akkermansia, Alloprevotella, Tidjanibacter, and Faecalibaculum demonstrated increased abundance. Correlation analysis identified Muribaculum, Paramuribaculum, Lacrimispora, and Turicibacter as microbial taxa associated with T2DM progression. RPPs significantly alleviated hyperglycemic symptoms in T2DM mice while enhancing the presence of beneficial gut bacteria, leading to a marked improvement in intestinal microbiota composition. This research offers foundational insights for the potential use of R. philippinarum in biomedical and nutraceutical applications.

Observational studies have shown that the gut microbiota (GM) is associated with bone diseases, particularly calcium-phosphorus metabolic bone diseases, demonstrating the existence of a gut-bone axis. However, whether these associations are causal effects remains to be determined. This study employed bidirectional two-sample Mendelian randomisation (MR) using summary data from Genome-Wide Association Studies (GWAS) of 211 gut microbial taxa and six metabolic bone diseases (osteoporosis, Osteopenia, osteonecrosis, osteomyelitis, hypoparathyroidism and hyperparathyroidism) to explore causal relationships and their directionality. Comprehensive sensitivity analyses were conducted to ensure the robustness of the results, and a false discovery rate-corrected pFDR of < 0.05 was used as a threshold to support strong associations. Additionally, co-localisation analysis was conducted to consolidate the findings. We identified 35 causal relationships between GM and metabolic bone diseases, with 17 exhibiting positive and 18 negative correlations. Furthermore, reverse MR analysis indicated that osteomyelitis was associated with elevated abundance of two GMs (pFDR < 0.05, PP.H4 < 75%). No evidence of horizontal pleiotropy or heterogeneity was observed, and co-localisation analysis further strengthened the evidence for these causal relationships. The study underscores the critical role of GM in influencing bone health through the gut-bone axis, paving the way for future therapeutic interventions targeting the gut-bone axis and offering new directions for research in bone metabolism and diseases.

Steamed Polygonatum sibiricum is widely applied in clinical practice for its tonic effect on gastrointestinal tract. A novel polysaccharide named PSSP-EF was extracted from the steamed roots of Polygonatum sibiricum using hot water extraction, ethanol precipitation, and chromatographic purification. PSSP-EF, with a molecular weight of 2.24 × 104 Da, was consisted of mannose, glucosamine hydrochloride, glucose, galactose, xylose, and arabinose in a molar ratio of 10.25: 0.26: 3.56: 80.55: 1.72: 3.66, and its main chain was constituted by→4)-β-D-Galp-(1→4)-β-D-Galp-(1→ and →4)-β-D-Manp-(1→4)-β-D-2ace-Manp-(1→ residues, with branching from β-D-Galp-(1→ residues. PSSP-EF could dramatically relieve clinical symptoms of ulcerative colitis (UC) in mice. Treatment with PSSP-EF significantly alleviated colon inflammation (TNF-α, IL-1β, and IL-6), repaired intestinal mucosal barrier (Occludin, ZO-1, and Claudin-1) and regulated the balance of gut microbiota by increased the levels of Muribaculaeae, while decreasing the levels of Bacteroides, Erysipelatoclostridium, and Romboutsia. Notably, PSSP-EF remarkably increased the levels of acetic, propionic, isobutyric, butyric, valeric, and isovaleric acid in the cecal contents of UC mice. In conclusion, PSSP-EF has a significant therapeutic effect on UC by balancing gut microbiota, protecting intestinal mucosal barrier, and regulating short-chain fatty acid production, and can be developed as a functional food.

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.