The gut microbiota plays an important role in maintaining host health by affecting various physiological functions. Among the diverse microbial communities in the gut, prophages are integral components of bacterial genomes, contributing significantly to bacterial evolution, ecology and pathogenicity. Prophages are capable of switching to lytic cycles in response to various internal and external factors. Factors that induce prophage induction include DNA damage, oxidative stress, nutrient availability, host immune response, quorum sensing, diet, secondary metabolites, antibiotics, and lifestyle changes. Prophage induction could contribute to both gut homeostasis and dysbiosis. Importantly, the connections between prophage induction and disorders such as inflammatory bowel disease, ulcerative colitis, and bacterial vaginosis highlight the dual roles of prophages in both health and disease. Although therapeutic approaches such as phage therapy (PT), fecal microbiota transplants (FMT), and fecal virome transplants (FVT) have gained attention, the concept of dietary prophage induction therapy offers a novel, targeted method to modulate gut microbiota. In spite of recent advances in understanding the role of prophages in gut health, the exact mechanisms by which they influence gut health remain only partially understood. Therefore, further research is needed to elucidate additional molecular mechanisms of prophage induction pathways and to explore their implications for gut microbiota dynamics and disease associations. This review discusses the molecular mechanisms and key factors that trigger prophage induction in the gut. Insights into these processes could lead to innovative therapeutic strategies that utilize prophages to support gut health.

Multi-strain probiotics have gained increasing attention for their ability to enhance host health by modulating the gut microbiota, immune responses, and resistance to pathogens. This study investigated the probiotic efficacy of KMK3, a novel three-strain consortium comprising Lactobacillus brevis (TN9), Ligilactobacillus salivarius (F9/2), and Ligilactobacillus salivarius (TL4/1), in broiler chickens, with a specific focus on pathogen resistance and immune modulation. Growth kinetics revealed that L. brevis (TN9) had the shortest lag phase (2 h) and the highest maximum optical density (OD600 ≈ 1.8), suggesting superior adaptation and growth compared to L. salivarius strains (lag phases: 6 and 4 h; OD600: 1.5 and 1.6, respectively). KMK3 administration significantly enhanced growth performance, with a 13 % higher body weight gain and an improved Feed Conversion Ratio (FCR: 1.50) compared to the control group (FCR: 1.75). The consortium also modulated immune responses, increasing serum antibody titers against Salmonella enterica lipopolysaccharides (4.5 ± 0.2 log10) and upregulating anti-inflammatory cytokine IL-10 while suppressing pro-inflammatory cytokines (IL-1β, TNF-α). Additionally, KMK3-treated chickens exhibited improved gut histopathology, including higher villus height and reduced immune cell infiltration, even under S. enterica challenge conditions. These findings highlight the ability of KMK3 to promote pathogen resistance, modulate immune mechanisms, and enhance gut health, offering insights into the molecular and functional interactions of probiotics in mitigating infectious challenges. This study highlights the therapeutic potential of multi-strain probiotics in advancing poultry health and productivity by targeting host-pathogen interactions and immune regulation.

Polychlorinated biphenyls (PCBs) are neurotoxic hazardous materials that may cause toxicity via the gut-liver-brain axis. This study investigated PCB × microbiome interactions in adult female mice exposed orally to an environmental PCB mixture. Female mice (6-week-old) were exposed daily for 7 weeks to peanut butter containing 0, 0.1, 1, or 6 mg/kg/day of PCBs. Twenty hours after the final exposure, the cecal content was collected to characterize the microbiome composition and predicted function. PCB and its metabolites in feces were analyzed using gas chromatography-tandem mass spectrometry (GC-MS/MS), while cecal content was assessed with liquid chromatography-high resolution mass spectrometry (LC-HRMS). PCB exposure influenced the abundance of microbial taxa and predicted functions within the cecal content. Complex PCB and metabolite mixtures were detected in the gastrointestinal tract. Network analysis revealed associations between specific parent PCBs and metabolites with changes in the abundance of bacteria in the gastrointestinal tract. These findings demonstrate that individual PCBs and their metabolites significantly influence the abundance of specific bacteria in the gastrointestinal tract following oral PCB exposure. These findings inform further research targeting the microbiome to attenuate the adverse health outcomes of PCB exposure.

The use of antibiotics unbalances the intestinal microbiota. Probiotics, prebiotics, and synbiotics are alternatives for these unbalances. The effects of a new synbiotic composed of probiotic Saccharomyces boulardii CNCM I-745 and fructans from Agave salmiana (fAs) as prebiotics were assessed to modulate the intestinal microbiota. Two probiotic presentations, the commercial probiotic (CP) and the microencapsulated probiotic (MP) to improve those effects, were used to prepare the synbiotics and feed Wistar rats subjected to antibiotics (AB). Eight groups were studied, including five controls and three groups to modulate the microbiota after the use of antibiotics: G5: AB + MP-synbiotic, G6: AB + CP-synbiotic, and G8: AB + fAs. All treatments were administered daily for 7 days. On days 7 and 21, euthanasia was performed, cecum tissue was recovered and used to evaluate histological analysis and to study microphotograph by TEM, and finally, bacterial DNA was extracted and 16S rRNA gene metabarcode sequencing was performed. Histological analysis showed less epithelial damage and more abundance of the intestinal microbiota in the groups G5, G6, and G8 in comparison with the AB control group after 7 days. Microphotograph of the cecum at 2 weeks post treatment showed that G5 and G6 presented beneficial effects in epithelial reconstruction. Interestingly, in the groups that used the synbiotic without AB (G3 and G4) in addition to contributing to the recovery of the autochthonous microbiota, it promotes the development of beneficial microorganisms; those results were also achieved in the groups that used the synbiotic with AB enhancing the bacterial diversity and regulating the impact of AB.

Chicken meat is an essential source of high-quality animal protein, mainly derived from slow-growth chicken (SC) and fast-growth chicken (FC) breeds. Skeletal muscle is a highly adaptable tissue that is influenced by breed differences and the gut microbiome. Investigation whether remodeling the gut microbiota by fecal microbiota transplantation (FMT) improves chicken growth is an interesting question. We compared the gut microbial composition of eight breeds of SC (Xinghua chicken, Yangshan chicken, Zhongshan Salan chicken, Qingyuan Partridge chicken, Huiyang Bearded chicken and Huaixiang chicken) and FC (Xiaobai chicken and White rock chicken). Fecal microbiota from donor FC (Xiaobai chickens) with superior growth performance were transferred to SC (Xinghua chickens). The effects of FMT on growth performance, metabolic profile and gut microbiome of recipient chickens were evaluated. We found significant differences in gut microbial composition, with a higher abundance of Bacteroidetes in SC and a higher abundance of Firmicutes in FC. Xiaobai chickens with better growth performance and abundant Lactobacillus, and FMT significantly enhanced growth performance, the expression of mRNA (MYOG, MYF5, MYF6 and IGF1) related to breast and leg muscle development and improved the villus/crypt ratio in the jejunum. FMT altered the microbiota in the duodenum, jejunum, and ileum, increased Lactobacillus abundance, decreased the relative mRNA expression of the intestinal inflammatory factors (IL-1β, IL-6 and TNF-α), increased glutamine levels in the host, including in muscle tissues and intestinal contents, and Spearman correlation analysis indicated that the relative abundance of Lactobacillus was positively correlated with glutamine levels. Additionally, antibiotic treatment reduces glutamine levels in the intestines, blood, and muscle tissues of chickens. Glutamine can increase the expression of cyclinD1, cyclinD2, cyclinB2, MYOG, MYF5, MYF6 and IGF1 mRNA to promote chicken myoblasts proliferation and differentiation. This study found that the SC and FC gut microbes were significantly different, and the FC chicken gut microbes were able to reshape the FC gut microbiota through FMT, i.e., higher Lactobacillus, promoted chicken myoblasts proliferation and differentiation and growth performance by increasing glutamine levels.

The study of bacterial diversity in human samples is crucial for developing biomarkers of health and disease. This research characterized the taxonomic and functional diversity of the anorectal bacterial microbiota in men who hae sex with men (MSM) with HIV compared to men from this group without HIV.

In July and August 2023, self-collected anorectal swabs were obtained. DNA was extracted from each sample, and metagenomic sequencing was performed. With the obtained data, alpha and beta diversity, bacterial abundance, differential operational taxonomic units, and functional diversity were determined.

Initially, 90 samples were collected, with 20 discarded due to having less than 200 ng of DNA and 15 due to incomplete sequencing, leaving 55 samples analysed (15 HIV-positive and 40 HIV-negative). No significant differences were found between groups in terms of alpha diversity (Shannon index p = 0.45) and beta diversity (PERMANOVA R = -0.03). Prevotella was identified as the most abundant genus in both groups. Twelve genes were found to be more abundant in the anorectal microbiota of the HIV group, which promote bacterial growth, colonization and survival.

Alterations in the anorectal microbiota could influence the pathogenesis of HIV and its complications in this population, underscoring the need to investigate these mechanisms and explore interventions to improve health. Longitudinal studies are needed to analyse changes in the anorectal microbiota during HIV infection and its response to treatment, integrating metagenomic, clinical, and immunological data to better understand the interactions between HIV, the microbiota and host health.

Gut microbiota composition has been implicated in surgical site complications after colorectal cancer surgery. Antibiotics affect gut microbiota, but evidence for a role in surgical site complications is inconclusive. We aimed to investigate use of prescription antibiotics during the years before surgery in relation to the risk of surgical site infections, including anastomotic leakage, within 30 days after surgery. Cardiovascular/neurological complications and the urinary antiseptic methenamine hippurate, for which there is no clear link with the microbiota, were used as negative controls. We conducted a patient cohort study using complete population data from Swedish national registers between 2005 and 2020. The final study population comprised 26,527 colon cancer and 12,312 rectal cancer cases with a 4.5 year exposure window. In colon cancer patients, antibiotics use was associated with a higher risk of surgical site infections (adjusted odds ratio (aOR) for any versus no use = 1.20, 95% confidence interval (CI) 1.10-1.33) and anastomotic leakage in particular (aOR =1.19, 95% CI 1.03-1.36), both with dose-response relationships for increasing cumulative antibiotics use (Ptrend = <0.001 and Ptrend = 0.047, respectively). Conversely, associations in rectal cancer patients, as well as for the negative controls cardiovascular/neurological complications and methenamine hippurate, were null. In conclusion, prescription antibiotics use up to 4.5 years before colorectal cancer surgery is associated with a higher risk of surgical site infections, including anastomotic leakage, after colon cancer but not rectal cancer surgery. These findings support a role for antibiotics-induced intestinal dysbiosis in surgical site infections.

Microbial communities are not simply remnants of the past but dynamic entities that continuously evolve under the selective pressures of nature, reflecting the intricate and adaptive processes of evolution. The microbiota residing in the various regions of the human body has numerous roles in different physiological processes such as nutrition, metabolism, immune regulation, etc. In the zeal of achieving empirical insights into the ambit of the gut microbiome, the research over the years led to the revelation of reciprocal interaction between the gut microbiome and the cognitive functioning of the human body. Dysbiosis in the gut microbial composition disturbs the homeostatic cognitive functioning of the human body. This dysbiosis has been associated with various chronic diseases, including brain cancer, such as glioma, glioblastoma, etc. This review explores the mechanistic role of dysbiosis-mediated progression of brain cancers and their subtypes. Moreover, it demonstrates the regulatory role of microbial metabolites produced by the gut microbiota, such as short-chain fatty acids, amino acids, lipids, etc., in the tumour progression. Further, we also provide valuable insights into the microbiota mediating the efficiency of therapeutic regimens, thereby leveraging gut microbiota as potential biomarkers and targets for improved treatment outcomes.

Obesity is recognized as a global epidemic that can result in changes in the human body and metabolism. Accumulating evidence indicates that gut microbiota (GM) can affect the development of obesity. The GM not only plays a crucial role in digesting and absorbing nutrients, but also in maintaining the overall health of the host. Dietary supplements such as non-starch polysaccharides are mainly fermented by the GM in the colon. Recent findings suggest that shaping the GM through the prebiotic function of non-starch polysaccharides may be a viable strategy against obesity. In this paper, the effects of non-starch polysaccharides on host health, together with their prebiotic function influencing the GM to control obesity via the gut-target organ axis, are reviewed. Potential perspectives of non-starch polysaccharides exhibiting anti-obesity effects via the gut-target organ axis are proposed for future research.

The human microbiota comprises a diverse microbial ecosystem that significantly impacts health and disease. Among its components, the gut microbiota plays a crucial role in regulating metabolic, immunologic, and inflammatory responses. Dysbiosis, an imbalance in microbial composition, has been linked to carcinogenesis through mechanisms such as chronic inflammation, metabolic disturbances, epigenetic modifications, and immune system dysregulation. Additionally, dysbiosis influences the efficacy and toxicity of cancer therapies. Given these associations, there is growing interest in leveraging the microbiota as a biomarker for cancer detection and outcome prediction. Notably, distinct microbial signatures have been identified across various cancer types, suggesting their potential as diagnostic markers. Furthermore, modulation of the microbiota presents a promising avenue for improving cancer treatment outcomes through strategies such as antibiotics, prebiotics, probiotics, fecal microbiota transplantation, dietary interventions, small-molecule inhibitors, and phage therapy. To explore these relationships, we conducted a comprehensive literature review using Web of Science, Scopus, PubMed, MEDLINE, Embase, and Google Scholar as our primary online databases, focusing on indexed peer-reviewed articles up to the present year. This review aims to elucidate the role of dysbiosis in cancer development, examine the molecular mechanisms involved, and assess the impact of microbiota on cancer therapies. Additionally, we highlight microbiota-based therapeutic strategies and discuss their potential applications in cancer management. A deeper understanding of the intricate interplay between the microbiota and cancer may pave the way for novel approaches to cancer prevention, early detection, and treatment optimization.

The extensive use of antibiotics in animal husbandry, either for therapeutic purposes or as growth promoters, has raised significant concerns about their effects on poultry. However, when antibiotics are used as therapeutic agents, their impact on the gut microbiota of poultry remains unknown. This study aimed to address this gap by simulating therapeutic application of six frequently used antibiotics (lincomycin hydrochloride, gentamicin sulfate, florfenicol injection, benzylpenicillin potassium, ceftiofur sodium, and enrofloxacin infection) and investigated their effects on the composition and structure of poultry gut microbiota. Single-molecule real-time 16S rRNA sequencing was performed to analyze fecal samples collected from chickens treated with each antibiotic to assess the impact of antibiotic exposure on gut community diversity and dominant microbial species. Although the results demonstrated that antibiotic exposure reduced gut microbiota diversity and disrupted community stability, the impacts of different antibiotics differed considerably, specifically in the number of ASVs. Notably, the dominant bacterial phyla-Pseudomonadota and Bacillota-was largely consistent across different antibiotic exposures, except 11 days after gentamicin sulfate exposure. Moreover, six third-category pathogens were identified in fecal samples, namely, Shigella boydii, Escherichia coli, Shigella flexneri, Salmonella enterica, Corynebacterium bovis, Proteus mirabilis. Of these, three strains of Corynebacterium bovis were identified as potential novel pathogenic bacteria. These findings demonstrate the critical importance of rational antibiotics use in animal husbandry. This study provides a scientific basis for improving current antibiotics use in the treatment and prevention of poultry diseases, advancing the standardization and precision of antibiotic usage.

Gestational diabetes mellitus (GDM) increasingly affects women and predisposes both mothers and their infants to short- and long-term health consequences. Emerging research links GDM to maternal gut microbiota dysbiosis. However, the impact of GDM on the infant gut microbiota remains unclear. This cross-sectional study aims to explore potential associations between GDM and the gut microbiota in mothers and their infants, as well as correlations between maternal diet, cardiometabolic profile, and gut microbiota composition.

Gut microbiota taxonomic composition was characterized by 16S rRNA gene sequencing on fecal samples collected at 2 months postpartum from 28 mothers, including 17 with (GDM+) and 11 without (GDM-) GDM, as well as 30 infants, 17 GDM + and 13 GDM-. Variations in overall composition and specific taxa between GDM + and GDM- were assessed. Correlations between maternal cardiometabolic profile, dietary intakes, and taxa were performed.

GDM was associated with the overall composition of gut microbiota between GDM + and GDM- in the maternal group, but not in infants. No statistically significant difference in alpha diversity between groups was found in either mothers or infants. However, 14 taxa showed significantly different abundance between GDM + and GDM- mothers, and 4 taxa differed in infants. Specific taxa at the family rank were correlated with maternal dietary and cardiometabolic variables in both mothers and infants.

GDM exposition was associated with gut microbiota composition in both mothers and infants at two months postpartum. This study enhances our understanding of how maternal health could be linked with the gut microbiota of mothers and their infants.

NCT02872402 (2016-08-04, https://clinicaltrials.gov/study/NCT02872402?term=NCT02872402&rank=1 ) and NCT04263675 (2020-02-07, https://clinicaltrials.gov/study/NCT04263675?term=NCT04263675&rank=1 ).

Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.

Similarity between candidate drug targets and human proteins is commonly assessed to minimize the occurrence of side effects. Although numerous drugs have been found to disrupt the health of the human microbiome, no comprehensive comparison between established drug targets and the human microbiome metaproteome has yet been conducted. Therefore, herein, sequence and structure alignments between human and pathogen drug targets and representative human gut, oral, and vaginal microbiome metaproteomes were performed. Both human and pathogen drug targets were found to be similar in sequence, function, structure, and drug binding capacity to proteins in diverse pathogenic and non-pathogenic bacteria from all three microbiomes. The gut metaproteome was identified as particularly susceptible overall to off-target effects. Certain symptoms, such as infections and immune disorders, may be more common among drugs that non-selectively target host microbiota. These findings suggest that similarities between human microbiome metaproteomes and drug target candidates should be routinely checked.

Background and Aim: The human gut microbiome plays a crucial role in maintaining health. Artificial sweeteners, also known as non-nutritive sweeteners (NNS), have garnered attention for their potential to disrupt the balance of the gut microbiome. This review explores the complex relationship between NNS and the gut microbiome, highlighting their potential benefits and risks. By synthesizing current evidence, we aim to provide a balanced perspective on the role of AS in dietary practices and health outcomes, emphasizing the need for targeted research to guide their safe and effective use. Methods: A comprehensive literature review was conducted through searches in PubMed and Google Scholar, focusing on the effects of artificial sweeteners on gut microbiota. The search utilized key terms including "Gut Microbiome", "gut microbiota", "Eubiosis", "Dysbiosis", "Artificial Sweeteners", and "Nonnutritive Sweeteners". Results: NNS may alter the gut microbiome, but findings remain inconsistent. Animal studies often report a decrease in beneficial bacteria like Bifidobacterium and Lactobacillus, and an increase in harmful strains such as Clostridium difficile and E. coli, potentially leading to inflammation and gut imbalance. Disruptions in short-chain fatty acid (SCFA) production and gut hormone signaling have also been observed. However, human studies generally show milder or no significant changes, highlighting the limitations in translating animal model findings directly to humans. Differences in study design, dosage, exposure time, and sweetener type likely contribute to these varied outcomes. Conclusions: While NNS offer certain benefits, including reduced caloric intake and improved blood sugar regulation, their impact on gut microbiome health raises important concerns. The observed reduction in beneficial bacteria and the rise in pathogenic strains underscore the need for caution in NNS consumption. Furthermore, the disruption of SCFA production and metabolic pathways illustrates the intricate relationship between diet and gut health.

Heart failure (HF) has become an immense health concern affecting almost 1-2% of the population globally. It is a complex syndrome characterized by activation of the sympathetic nervous system and the Renin-Angiotensin-Aldosterone (RAAS) axis as well as endothelial dysfunction, oxidative stress, and inflammation. The recent literature points towards the interaction between the intestinal flora and the heart, also called the gut-heart axis. The human gastrointestinal tract is naturally inhabited by various microbes, which are distinct for each patient, regulating the functions of many organs. Alterations of the gut microbiome, a process called dysbiosis, may result in systemic diseases and have been associated with heart failure through inflammatory and autoimmune mechanisms. The disorder of intestinal permeability favors the translocation of microbes and many metabolites capable of inducing inflammation, thus further contributing to the deterioration of normal cardiac function. Besides diet modifications and exercise training, many studies have revealed possible gut microbiota targeted treatments for managing heart failure. The aim of this review is to demonstrate the impact of the inflammatory environment induced by the gut microbiome and its metabolites on heart failure and the elucidation of these novel therapeutic approaches.

Mycotoxins perturb the gut microbiota performance. Bioactive compounds have been recently used as a new food strategy to diminish mycotoxins bioaccessibility and prevent their toxic effects on human and animal health. Male and female Wistar rats were exposed orally to twelve different diets containing aflatoxin B1 (AFB1) and/or ochratoxin A (OTA) with or without fermented whey (FW) and pumpkin (P) for 28 days. Fecal microbiota using 16S rRNA gene sequencing and subsequent metagenomics analysis were analyzed to study the effect of 28-day exposure through diet of contaminated and enriched feed. QIIME 2 microbiome analysis package (version 2024.5) was used to analyze the demultiplexed data. Mycotoxins-functional ingredients combination contributed more to microbial phylogenetic faith α-diversity rather than the functional ingredients alone, while the same combination reported a microbial α-diversity enhancement in comparison to the mycotoxins alone. Proteobacteria phylum was reduced in rat samples fed with contaminated diets (AFB1, OTA, and AFB1+OTA), while there was an increase-although not in all groups-when adding the functional ingredients. The main difference between the sexes was found in FW+AFB1+OTA group, with males (25%) showing higher % of Proteobacteria than females (1.86%). Phylogenetic diversity faith only focuses on microbial genetic (dis)similarity, not considering the biological function. Morganella morganii, a Proteobacteria found in some groups presents anticancer activity, but it is also related to inflammatory bowel disease and colorectal cancer. To sum up, both mycotoxins and functional ingredients trigger changes in the microbiota profile of Wistar rats in a sex-specific manner.

Microbiota may play a role in autoimmune disease pathogenesis, including multiple sclerosis (MS). Antibiotic use disrupts the microbiome and may increase the risk of autoimmune diseases. We evaluated the relationship between MS diagnosis and antibiotic, antimycotic and antiviral drug use in the 5 years preceding diagnosis.

Our population-based case-control study used German ambulatory claims data from 2012 to 2022. We defined cohorts of 13,053 MS patients, 22,898 Crohn's disease patients, and 15,037 matched controls without autoimmune diseases, aged 21-70. Logistic and Poisson regression models explored the relationship between MS diagnosis and antimicrobial usage. Two sub-analyses were performed: a separate analysis of patients with clinically isolated syndrome (CIS) and a sensitivity analysis of newly diagnosed MS patients without preceding neurological symptoms.

Patients with MS had higher exposure to antibiotic (Odd Ratio (OR) = 1.27, 95 % CI 1.21-1.33), antimycotic (OR = 1.27, 95 % CI 1.12-1.45), and antiviral drugs (OR = 1.28, 95 % CI 1.15-1.43) in the five years before diagnosis compared to patients with no autoimmune diseases. Similar findings were obtained for the CIS cohort and in the sensitivity analysis. Antibiotic use peaked 5 years before MS diagnosis, declining closer to diagnosis, while antiviral and antimycotic drug use showed the opposite. This effect was not observed in the sensitivity analysis and CIS cohorts. Antibiotic use was higher in Crohn's disease than in MS (OR = 0.86, 95 % CI 0.82-0.90), with no consistent differences in antimycotic and antiviral use.

The association and kinetic of antibiotic use before MS and CIS diagnosis supports the role of microbiota in MS pathogenesis and suggests antibiotic use to be related to the development of autoimmune diseases, including MS. Additional studies are warranted to clarify whether increased antibiotic use is part of the MS prodrome or a true risk factor for MS.

Gut microbiota plays an essential role in cognitive dysfunction during aging. The aim of this study was to investigate the dynamic alterations in the gut microbiota and screen for key gut bacterial taxa correlated with age-associated cognitive dysfunction during natural aging.

16S rRNA gene sequencing was performed to determine the composition of the gut microbiota in faecal samples from SAMR1 and SAMP8 mice, cognitively normal controls (NC), and patients with amnestic mild cognitive impairment (aMCI). Faecal microbiota transplantation (FMT) and GMrepo database were used to screen key gut microbiota associated with cognitive decline in aging mice and humans.

The composition of the gut microbiota dynamically changed during natural aging in SAMR1 and SAMP8 mice, as well as in healthy subjects of different ages extracted from the GMrepo database. FMT from SAMR1 to SAMP8 mice altered the gut microbiota composition and improved the cognitive impairment in SAMP8 mice. Key gut bacterial taxa, including Lactobacillus, Akkermansia, Clostridium, Oscillospira and Dorea, were screened and validated to correlate with aging-associated cognitive decline. The function of the key gut bacterial taxa predicted by PICRUSt2 indicated that the metabolic pathways related to short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS) synthesis were involved in age-associated cognitive dysfunction during natural aging.

These results demonstrate that the composition of the gut microbiota changes dynamically during brain aging, with some key gut bacterial taxa playing critical roles in age-associated cognitive dysfunction through SCFAs and LPS synthesis metabolic pathways.

Amphibians are the most severely threatened vertebrate group in terms of biodiversity. The microbiota that coexist in a mutualistic relationship with amphibians play a crucial role in shaping their health status, reproductive efficiency, and environmental adaptability. Understanding the relationship between amphibians and microbiota is vital for elucidating the causes of amphibian diseases and developing effective prevention and control techniques, which in turn is significant for enhancing the effectiveness of amphibian diversity conservation. The main findings of this article are as follows: Firstly, it provides an overview of the systematic assessment and analysis methods regarding the importance of amphibians and their symbiotic microbiota, detailing the primary research techniques currently employed. Secondly, it discusses the impacts of environmental and biological factors on the characteristics of amphibian symbiotic microbial communities, including dimensions such as altitude, temperature fluctuations, and host dietary habits. Finally, the future directions of research on amphibian symbiotic microbiota are examined, with five recommendations presented: (1) Establish a comprehensive sample library and database of amphibians and their symbiotic microbiota to create a solid foundation for scientific research. (2) Explore the coevolutionary paths between amphibians and symbiotic microbiota to clarify the dynamic evolutionary patterns and principles of their interactions. (3) Strengthen research on specific areas of amphibians, especially the microbial communities in the oral cavity and cloaca. (4) Enhance research on the symbiotic microbiota of the Gymnophiona. (5) Strengthen international cooperation to build cross-border research platforms and jointly promote the rapid development of global amphibian symbiotic microbiology. This article summarizes the current research progress on the interaction between amphibians and their symbiotic microbiota (not necessarily mutualistic). It discusses the conservation of amphibian biodiversity from the perspective of their symbiotic microbial communities and provides a forward-looking analysis of future research directions. It aims to provide rich background information for understanding the complexity of this symbiotic system, while also having significant value in enhancing the effectiveness of amphibian biodiversity conservation.

Music intervention is gaining recognition as a cost-effective therapeutic for improving human health. Despite its growing application, the mechanisms through which music exerts beneficial health effects remain largely unexplored. Here, we show that music can exert beneficial effects in mice through modulating gut microbiome composition. Adult mice were exposed to ambient noise, Mozart's Flute Quartet in D Major, K. 285, or white noise over a three-week period. Afterward, we observed treatment-specific changes in the community of gut commensal bacteria in these animals. Upon subsequent challenge with the bacterial pathogen Salmonella typhimurium, control groups exhibited significant weight loss and increased Salmonella colonization, whereas the Mozart-treated group did not. 16S ribosomal RNA gene sequencing revealed that the Mozart group showed a significant increase in Lactobacillus salivarius, a probiotic known for its antibacterial properties. Further experiments confirmed that L. salivarius mitigated Salmonella infection in mice and that L. salivarius acidified local environments in in vitro culture, thus inhibiting Salmonella growth. Additionally, mice exposed to Mozart consumed more food but showed similar body weight compared to the control groups. Behavioral assessments, including open field and object location tests, revealed that Mozart-treated mice were more active, less anxious, and exhibited enhanced spatial memory. Finally, Mozart exposure was shown to significantly boost colonization of administered L. salivarius and alter gut metabolite profiles. These findings suggest that music exposure fosters healthier gut microbiota, enhancing resistance to bacterial infections and highlighting the potential of music therapy as a novel strategy to combat drug-resistant pathogen infections.

Music therapy is increasingly recognized as a low-cost approach to improving health, but how it works remains unclear. Our study demonstrates that music can positively influence health by altering the gut microbiome. In a mouse model, exposure to Mozart's Flute Quartet in D Major enhanced the gut microbiota, specifically increasing levels of the beneficial bacterium Lactobacillus salivarius. This probiotic protected mice from Salmonella infection by creating an acidic environment that inhibited pathogen growth. Mozart-treated mice also showed reduced anxiety, better spatial memory, and higher food intake without weight gain, suggesting the benefits of music exposure. These findings reveal a novel link between music, gut health, and disease resistance, suggesting that music therapy could be a promising strategy for enhancing gut microbiota and combating infections, including those caused by drug-resistant bacteria.

Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The gut microbiome interacts with the liver via a bidirectional relationship with the gut-liver axis. Microbial metabolites, sirtuins, and immune responses are pivotal in different metabolic diseases. This extensive review explores the complex and multifaceted interrelationship between sirtuins and gut microbiota, highlighting their importance in health and disease, particularly metabolic dysfunction and hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as a group of NAD+-dependent deacetylases, serve as crucial modulators of a wide spectrum of cellular functions, including metabolic pathways, the inflammatory response, and the process of senescence. Their subcellular localization and diverse functions link them to various health conditions, including NAFLD and cancer. Concurrently, the gut microbiota, comprising diverse microorganisms, significantly influences host metabolism and immune responses. Recent findings indicate that sirtuins modulate gut microbiota composition and function, while the microbiota can affect sirtuin activity. This bidirectional relationship is particularly relevant in metabolic disorders, where dysbiosis contributes to disease progression. The review highlights recent findings on the roles of specific sirtuins in maintaining gut health and their implications in metabolic dysfunction and HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked to metabolic dysregulation and liver pathology.

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.

The intricate interplay between natural compounds like curcumin and the gut microbiome has gained significant attention in recent years due to their potential therapeutic implications in various health conditions. Curcumin, a polyphenolic compound derived from turmeric, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, and anticancer effects. Understanding how curcumin modulates gut microbiota composition and function is crucial for elucidating its therapeutic mechanisms. This review examines the current literature on the interactions between curcumin and the gut microbiome. A systematic search of relevant databases was conducted to identify studies investigating the effects of curcumin on gut microbial diversity and abundance. Key findings from studies exploring curcumin's efficacy in neurological disorders, gastrointestinal diseases, and metabolic dysfunction are synthesized and discussed. Studies have demonstrated that curcumin supplementation can modulate gut microbiota composition and function, leading to beneficial effects on gut health and homeostasis. Mechanisms underlying curcumin's therapeutic effects include immune modulation, neuroprotection, and inflammation regulation. However, challenges such as poor bioavailability and safety concerns remain significant hurdles to overcome. The interactions between curcumin and the gut microbiome hold promise for therapeutic interventions in a diverse range of health conditions. Further research is needed to optimize curcumin formulations, improve bioavailability, and address safety concerns.

Immune checkpoint inhibition is a major component in today's cancer immunotherapy. In recent years, the FDA has approved a number of immune checkpoint inhibitors (ICIs) for the treatment of melanoma, non-small-cell lung, breast and gastrointestinal cancers. These inhibitors, which target cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1) checkpoints have assumed a leading role in immunotherapy. The same inhibitors exert significant antitumor effects by overcoming tumor cell immune evasion and reversing T-cell exhaustion. The initial impact of this therapy in cancer treatment was justly described as revolutionary, however, clinical as well as research data which followed demonstrated that these innovative drugs are costly, are associated with potentially severe adverse effects, and only benefit a small subset of patients. These limitations encouraged enhanced research and clinical efforts to identify predictive biomarkers to stratify patients who are most likely to benefit from this form of therapy. The discovery and characterization of this class of biomarkers is pivotal in guiding individualized treatment against various forms of cancer. Currently, there are three FDA-approved predictive biomarkers, however, none of which on its own can deliver a reliable and precise response to immune therapy. Present literature identifies the absence of precise predictive biomarkers and poor understanding of the mechanisms behind tumor resistance as the main obstacles facing ICIs immunotherapy. In the present text, we discuss the dual role of PD-L1 as a biomarker for response to immunotherapy and as an immune checkpoint. The contribution of mass spectrometry-based analysis, particularly the impact of protein post-translational modifications on the performance of this protein is underlined.

The gut microbiome and human body have co-evolved in a synergistic host-microbial relationship. The ideal composition of human gut microbiota is an elusive concept, but every individual has a unique gut microbiota profile with regional differences. Newer diagnostic techniques have helped identify different bacteria and their roles in health and disease. The gut microbiome composition is affected by various factors like age, diet, immune system, environmental factors, exercise, and drugs. The microbiome has varied roles in metabolism, immune response, immune tolerance and antimicrobial protection. Diet plays an important role in maintaining the gut microbial diversity. Loss of homoeostasis in the microbiome results in dysbiosis. Dysbiosis plays a role in many dermatological diseases like atopic dermatitis, psoriasis, acne, rosacea, hidradenitis suppurativa, connective tissue disorders and many other systemic conditions like obesity, diabetes, neurological disease and malignancy. Reconstitution of the gut microbiome ecology in the form of bacteriotherapy with the reintegration of certain strains of microbiota has a beneficial role in many of these disorders.

The human gut flora of trillions of bacteria is vital for general health and greatly influences digestion, immune system function, and brain development. Through neuronal, hormonal, and immunological channels, the gut-brain axis (GBA), a bidirectional communication network, links the gut microbiota to the central nervous system (CNS). This relationship has been linked to affective diseases, including depression and anxiety, as well as mental health issues. This review explores the intricate relationship between gut bacteria and mood disorders, focusing on how gut microbiota-host interactions, immune system modulation, and neurotransmitter control support mental health. The function of important microbial metabolites, including short-chain fatty acids (SCFAs), in preserving blood-brain barrier integrity and modulating neuroinflammation is covered in this review. It also examines the bidirectional impact between gut health and mental health, including how dysbiosis could aggravate mood disorders and how depressed states might change the composition of gut bacteria. Furthermore, we discuss how psychotropic drugs affect gut flora and consider other elements such as nutrition and lifestyle that affect gut microbiome composition. Potential paths for treating mood disorders through gut microbiota modification are presented as emerging treatment techniques, including probiotics, nutritional therapies, and precision medicine. The development of new therapeutic approaches for mood disorders depends on the awareness of the GBA. Gut bacteria significantly affect mental health through immune modulation, neurotransmitter generation, and other intricate processes. Future studies should concentrate on large, varied populations to better understand these interactions and to create customized treatments that combine gut microbiota modulation with conventional mental health therapies.

Capillaria hepatica, a zoonotic parasite, is present in the population of Brandt's voles (Lasiopodomys brandtii) and has been a central issue in ecological studies regarding its impact on host populations. Brandt's voles are known for their extremely high reproductive capacity, and the population explosion of Brandt's voles have occurred multiple times in the grasslands of Inner Mongolia over the past few decades. However, the mechanisms underlying the population dynamics of Brandt's voles, particularly in response to C. hepatica infection, remain poorly understood. Given the critical role of the gut microbiota in modulating hormones within the reproductive endocrine system, this study aims to explore how alterations in the gut microbiota influence the host's population dynamics in response to C. hepatica infection.

Female Brandt's voles were inoculated with eggs of infected C. hepatica, and BALB/C mice were used as a control. At the end of the experimental period, cecal contents were collected for 16 S rRNA amplicon sequencing, and the expression levels of reproductive-related hormones were determined using enzyme-linked immunosorbent assay (ELISA).

C. hepatica infection leads to an increased diversity of gut microbiota in Brandt's voles, with significant changes in microbial composition. The relative abundance of Muribaculaceae and Eubacteriaceae increased significantly, while that of Rikenellaceae and Lachnospiraceae decreased significantly. The expression level of estradiol in the serum of infected Brandt's voles shows a slight decrease without statistical significance. However, the expression of equol is significantly higher in the infected group compared to the uninfected group, and the expression of enterolactone is significantly lower in the infected group than in the uninfected group.

This study demonstrates that infection with C. hepatica indirectly affect the abundance of specific gut microbiota in Brandt's voles, which are associated with reproductive hormones. This indirect effect on hormone expression can subsequently impact the reproductive function of the host. By investigating the changes in specific gut microbiota, this study sheds light on the mechanisms through which parasites regulate population fluctuations in Brandt's voles.

Understanding changes to gut microbiota composition in response to hormonal birth control (HBC) may provide insight into the microbial mechanisms underlying the metabolic effects of HBC, for example, altered short-chain fatty acid (SCFA) production. Athletes' unique physiological demands may interact with these microbial mechanisms in distinct ways; however, there is limited research on HBC and gut microbiota diversity and composition across different menstrual cycle phases in physically active females. A pilot cohort of physically active females using HBC (oral contraceptives, hormone-based intrauterine devices, or arm implants) and a control group not using HBC (n = 12 per group; 22 ± 2 yr, 24 ± 4 kg/m2 vs. 22 ± 4 yr, 23 ± 4 kg/m2; Ps ≥ 0.496) provided fecal samples alongside self-reported menstrual phase and circulating sex hormones. α-diversity (microbial richness and evenness) was assessed using the Shannon index whereas β-diversity (microbial composition differences) was analyzed using PERMANOVA based on Bray-Curtis dissimilarity. Circulating estrogen and luteinizing hormone increased from early (days 1-5) to mid-cycle (days 12-17) in both groups (time effect Ps ≤ 0.01), with greater changes in Control (Ps ≤ 0.046) than HBC (Ps ≥ 0.231). Although no menstrual phase effect was observed on either diversity measure (Ps ≥ 0.473), β-diversity differed between Control and HBC groups (P = 0.015), reflecting distinct gut microbiota profiles irrespective of menstrual phase. Seven taxa linked to SCFA production were less abundant in the HBC group (unadjusted Ps ≤ 0.046), though significance was lost after adjusting for multiple comparisons. These findings suggest that in physically active females, hormonal contraception influences gut microbial composition, which may have downstream effects on metabolism and performance.NEW & NOTEWORTHY This study is the first to investigate interactions between hormonal contraception and the gut microbiota in a cohort of physically active young females across the menstrual cycle. Our findings suggest that hormonal contraception may influence gut microbiota composition, potentially through a reduced relative abundance of short-chain fatty acid-producing taxa. Experimental studies are needed to confirm these associations and explore their potential implications for metabolism, health, and performance.

Fecal metabolomics studies have garnered interest in recent years due to the potential for these samples to provide unique information about an individual. Stool is a dynamic mixture of human excrement, microbiota, and enzymes that yields a constantly changing metabolite profile. The main challenge in a fecal metabolomics study is ensuring that the metabolite profile changes as little as possible between sample collection and sample processing/analysis.

This study aimed to evaluate the efficacy of five solutions in preserving human fecal metabolites over a seven-day storage period at ambient temperature, enabling at-home collection, cost-effective ambient transport and sample storage.

Five solutions with varying chemical compositions were evaluated for their ability to stabilize fecal metabolites. Samples were stored at ambient temperature for seven days, and metabolites were analyzed using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS). The stabilizing efficacy of the solutions was assessed using total useful peak area (TUPA), absolute relative change (ARC) and compound class-based analyses, comparing the initial, stabilized, and unstabilized samples.

Different solutions demonstrated varied efficiencies for different compound classes. Overall, the results indicated that the use of stabilization solutions significantly minimized changes in the fecal metabolite profile compared to unstabilized samples left at room temperature for one week.

This study demonstrates that stabilization solutions are effective in preserving fecal metabolites during storage at ambient temperature, supporting the feasibility of at-home sample collection.

The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.

This study aimed to scrutinize variations in the intestinal microbiota of neonatal dogs born through natural birth versus elective cesarean section, focusing on evaluating the influence of vaginal seeding on the microbiota of cesarean-born neonates. Samples were collected from cesarean-sectioned females before anesthesia and from naturally birthing females during prodrome signs, along with neonates at eight time points from birth to 15 days of age. In the cesarean section group, seeding was performed in half of the neonates (cesarean section seeding group; seeding consisted of gently rubbing the gauze, obtained from the mother's vagina, onto the mouths, faces, and bodies of the newborns), while the other half underwent microbiological sample collection without seeding (cesarean section group). Another group (normal birth group) consisted of naturally born neonates. Microbiota analysis included counting for enterobacteria, Staphylococcus spp., and Streptococcus spp. The results suggested that vertical transmission played a crucial role, but the method of birth did not emerge as the primary determinant of observed differences. Under study conditions, vaginal seeding failed to effectively modulate the microbiota of neonates born through elective cesarean section. Further investigations into the gut-brain axis are suggested for understanding factors influencing the initial development of the canine intestinal microbiota in neonates born through different delivery routes.

Chitosan, a biopolymer derived from the deacetylation of chitin found in crustacean shells and certain fungi, has attracted considerable attention for its promising health benefits, particularly in gut microbiota maintenance and immune system modulation. This review critically examines chitosan's multifaceted role in supporting gut health and enhancing immunity, beginning with a comprehensive overview of its sources, chemical structure, and its dual function as a dietary supplement and biomaterial. Chitosan's prebiotic effects are highlighted, with a focus on its ability to selectively stimulate beneficial gut bacteria, such as Bifidobacteria and Lactobacillus, while enhancing gut barrier integrity and inhibiting the growth of pathogenic microorganisms. The review delves deeply into chitosan's immunomodulatory mechanisms, including its impact on antigen-presenting cells, cytokine profiles, and systemic immune responses. A detailed comparative analysis assesses chitosan's efficacy relative to other prebiotics and immunomodulatory agents, examining challenges related to bioavailability and metabolic activity. Beyond its role in gut health, this review explores chitosan's potential as a dual-action agent that not only supports gut microbiota but also fortifies immune resilience. It introduces emerging research on novel chitosan derivatives, such as chitooligosaccharides, and evaluates their enhanced bioactivity for functional food applications. Special attention is given to sustainability, with an exploration of alternative, plant-based sources of chitosan and their implications for both health and environmental stewardship. Also, the review identifies new research avenues, such as the growing interest in chitosan's role in the gut-brain axis and its potential mental health benefits through microbial interactions. By addressing these innovative areas, the review aims to shift the focus from basic health effects to chitosan's broader impact on public health. The findings encourage further exploration, particularly through human trials, and emphasize chitosan's untapped potential in revolutionizing health and disease management.

Individuals with inflammatory bowel disease (IBD) are at a higher risk of developing mental disorders, such as anxiety and depression. The imbalance between the intestinal microbiota and its host, known as dysbiosis, is one of the factors, disrupting the balance of metabolite production and their signaling pathways, leading to disease progression. A metabolomics approach can help identify the role of gut microbiota in mental disorders associated with IBD by evaluating metabolites and their signaling comprehensively. This narrative review focuses on metabolomics studies that have comprehensively elucidated the altered gut microbial metabolites and their signaling pathways underlying mental disorders in IBD patients. The information was compiled by searching PubMed, Web of Science, Scopus, and Google Scholar from 2005 to 2023. The findings indicated that intestinal microbial dysbiosis in IBD patients leads to mental disorders such as anxiety and depression through disturbances in the metabolism of carbohydrates, sphingolipids, bile acids, neurotransmitters, neuroprotective, inflammatory factors, and amino acids. Furthermore, the reduction in the production of neuroprotective factors and the increase in inflammation observed in these patients can also contribute to the worsening of psychological symptoms. Analyzing the metabolite profile of the patients and comparing it with that of healthy individuals using advanced technologies like metabolomics, aids in the early diagnosis and prevention of mental disorders. This approach allows for the more precise identification of the microbes responsible for metabolite production, enabling the development of tailored dietary and pharmaceutical interventions or targeted manipulation of microbiota.

Our study focused on a mouse model of obesity induced by a high-fat diet (HFD). We administered Semaglutide intraperitoneally (Ozempic ®-0.05 mg/Kg-translational dose) every seven days for six weeks. HFD-fed mice had higher blood glucose, lipid profile, and insulin resistance. Moreover, mice fed HFD showed high gut levels of TLR4, NF-kB, TNF-α, IL-1β, and nitrotyrosine and low levels of occludin, indicating intestinal inflammation and permeability, culminating in higher serum levels of IL-1β and LPS. Treatment with semaglutide counteracted the dyslipidemia and insulin resistance, reducing gut and serum inflammatory markers. Structural changes in gut microbiome were determined by 16S rRNA sequencing. Semaglutide reduced the relative abundance of Firmicutes and augmented that of Bacteroidetes. Meanwhile, semaglutide dramatically changed the overall composition and promoted the growth of acetate-producing bacteria (Bacteroides acidifaciens and Blautia coccoides), increasing hypothalamic acetate levels. Semaglutide intervention increased the number of hypothalamic GLP-1R+ neurons that mediate endogenous action on feeding and energy. In addition, semaglutide treatment reversed the hypothalamic neuroinflammation HDF-induced decreasing TLR4/MyD88/NF-κB signaling and JNK and AMPK levels, improving the hypothalamic insulin resistance. Also, semaglutide modulated the intestinal microbiota, promoting the growth of acetate-producing bacteria, inducing high levels of hypothalamic acetate, and increasing GPR43+ /POMC+ neurons. In the ARC, acetate activated the GPR43 and its downstream PI3K-Akt pathway, which activates POMC neurons by repressing the FoxO-1. Thus, among the multifactorial effectors of hypothalamic energy homeostasis, possibly higher levels of acetate derived from the intestinal microbiota contribute to reducing food intake.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by motor symptoms and non-motor symptoms. It has been found that intestinal issues usually precede motor symptoms. Microorganisms in the gastrointestinal tract can affect central nervous system through the microbiota-gut-brain axis. Accumulating evidence has shown that disturbances in the microbiota-gut-brain axis are linked with PD. Thus, this pathway appears to be a promising therapeutic target for treatment of PD.

In this review, we mainly described gut dysbiosis in PD and their underlying mechanisms for mediating neuroinflammation and peripheral immune response in PD pathology and futher discussed the potential small-molecule compounds and genic therapeutic strategies targeting the microbiota-gut-brain axis and their applications in PD.

Studies have found that some small molecule compounds and alterations of inflammation-related genes can improve the motor and non-motor symptoms of PD by improving the microbiota-gut-brain axis, which may provide potentially beneficial drugs and molecular targets for the therapies of PD.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and progressive neuronal damage. Recent research has highlighted the significant roles of the gut microbiota and microRNAs (miRNAs) in the pathogenesis of AD. This review explores the intricate interaction between gut microbiota and miRNAs, emphasizing their combined impact on Alzheimer's progression. First, we discuss the bidirectional communication within the gut-brain axis and how gut dysbiosis contributes to neuroinflammation and neurodegeneration in AD. Changes in gut microbiota composition in Alzheimer's patients have been linked to inflammation, which exacerbates disease progression. Next, we delve into the biology of miRNAs, focusing on their roles in gene regulation, neurodevelopment, and neurodegeneration. Dysregulated miRNAs are implicated in AD pathogenesis, influencing key processes like inflammation, tau pathology, and amyloid deposition. We then examine how the gut microbiota modulates miRNA expression, particularly in the brain, potentially altering neuroinflammatory responses and synaptic plasticity. The interplay between gut microbiota and miRNAs also affects blood-brain barrier integrity, further contributing to Alzheimer's pathology. Lastly, we explore therapeutic strategies targeting this gut microbiota-miRNA axis, including probiotics, prebiotics, and dietary interventions, aiming to modulate miRNA expression and improve AD outcomes. While promising, challenges remain in fully elucidating these interactions and translating them into effective therapies. This review highlights the importance of understanding the gut microbiota-miRNA relationship in AD, offering potential pathways for novel therapeutic approaches aimed at mitigating the disease's progression.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and significantly improved outcomes for patients with certain malignancies. However, immunotherapy with ICIs is only effective in a subset of patients and the gut microbiota have been identified as an important factor associated with response to ICI therapy. Polysaccharides from sea cucumber (Stichopus japonicus) (SCP) have been shown to modulate the gut microbiota and exhibit beneficial health functions, but whether SCP could synergize with anti-PD1 immunotherapy remains unexplored. In this study, mice with ICI-sensitive MC38 tumors were treated with anti-PD1 antibody after supplementation with or without SCP to examine the potential impact of SCP on the efficacy of immunotherapy. SCP strongly amplified the anti-tumor activity of anti-PD1 in MC38 tumor-bearing mice. Flow cytometry and immunohistological staining demonstrated that SCP treatment increased cytotoxic CD8+ T lymphocytes while decreasing regulatory Foxp3+ CD4+ T lymphocytes. Gut microbiota and metabolomic analysis revealed that SCP modulated the microbiota and increased the abundance of certain metabolites such as indole-3-carboxylic acid. Furthermore, fecal microbiota transplantation experiments justified that the synergistic effect of SCP with anti-PD1 was partially mediated through the gut microbiota. Mice receiving microbiota from SCP-treated mice showed a boosted response to anti-PD1, along with enhanced anti-tumor immunity. These findings indicate that SCP could be utilized as a dietary strategy combined with anti-PD1 therapy to achieve improved outcomes in patients.