Restriction of dietary carbohydrates, fat and/or protein is often used to reduce body weight and/or treat (metabolic) diseases. Since diet is a key modulator of the human gut microbiome, which plays an important role in health and disease, this review aims to provide an overview of current knowledge of the effects of macronutrient-restricted diets on gut microbial composition and metabolites. A structured search strategy was performed in several databases. After screening for inclusion and exclusion criteria, thirty-six articles could be included. Data are included in the results only when supported by at least three independent studies to enhance the reliability of our conclusions. Low-carbohydrate (<30 energy%) diets tended to induce a decrease in the relative abundance of several health-promoting bacteria, including Bifidobacterium, as well as a reduction in short-chain fatty acid (SCFA) levels in faeces. In contrast, low-fat diets (<30 energy%) increased alpha diversity, faecal SCFA levels and abundance of some beneficial bacteria, including Faecalibacterium prausnitzii. There were insufficient data to draw conclusions concerning the effects of low-protein (<10 energy%) diets on gut microbiota. Although the data of included studies unveil possible benefits of low-fat and potential drawbacks of low-carbohydrate diets for human gut microbiota, the diversity in study designs made it difficult to draw firm conclusions. Using a more uniform methodology in design, sample processing and sharing raw sequence data could foster our understanding of the effects of macronutrient restriction on gut microbiota composition and metabolic dynamics relevant to health. This systematic review was registered at https://www.crd.york.ac.uk/prospero as CRD42020156929.

Immunosenescence is the loss and change of immunological organs, as well as innate and adaptive immune dysfunction with ageing, which can lead to increased sensitivity to infections, age-related diseases, and cancer. Emerging evidence highlights the role of gut-vitamin D axis in the regulation of immune ageing, influencing chronic inflammation and systemic health. This review aims to explore the interplay between the gut microbiota and vitamin D in mitigating immunosenescence and preventing against chronic inflammation and age-related diseases.

Gut microbiota dysbiosis and vitamin D insufficiency accelerate immunosenescence and risk of chronic diseases. Literature data reveal that vitamin D modulates gut microbiota diversity and composition, enhances immune resilience, and reduce systemic inflammation. Conversely, gut microbiota influences vitamin D metabolism to promote the synthesis of active vitamin D metabolites with implications for immune health.

These findings underscore the potential of targeting gut-vitamin D axis to modulate immune responses, delay the immune ageing, and mitigate age-related diseases. Further research is needed to integrate vitamin D supplementation and microbiome modulation into strategies aimed at promoting healthy ageing.

Research on Bacillus thuringiensis (Bt)-pest interactions has prioritized Cry toxin receptors, with limited attention to gut bacteria's role in modulating Bt sensitivity. This study identified two Enterobacter strains in Plutella xylostella with opposing effects on Cry1Ac susceptibility. Enterobacter hormaechei (PxG15) degraded Cry1Ac protoxin and activated the proPO-AS and JNK pathway, which reduced Cry1Ac's damage to the midgut while limiting the invasion of gut bacteria into the hemolymph. Although Enterobacter asburiae (PxG1) rapidly activated the proPO-AS, the JNK pathway was activated in a much slower and weaker mode when compared to PxG15, which attenuated the repairing efficiency of the midgut under the treatment of Cry1Ac, leading to death resulting from sepsis from the quick invasion of gut bacteria into the hemolymph. This study illustrates the intricate interrelationships among Cry1Ac, the pest's midgut bacteria, and its immune system, offering novel insights into how gut bacteria shape pest survival following Cry1Ac exposure.

The growth of different grafted guava was different as affected by grafting on different rootstock varieties, which also influenced the damage degree of Spodoptera litura larvae. The co-regulation of the pest gut by rhizosphere microorganisms and root exudates may contribute to this differential damage. In this study, the microorganisms of soil, plants, S. litura larvae and root exudates of guava grafted on different rootstock varieties were analysed and compared. The activities of superoxide dismutase, peroxidase and catalase in the midgut of S. litura larvae feeding on heterograft leaves of guava (where rootstock and scion are of the different variety) were significantly higher than those in the midgut of S. litura larvae feeding on homograft leaves of guava (where rootstock and scion are of the same variety), and glutathione s-transferase activity showed an opposite result. Enterococcus spp. and Escherichia spp. were the two bacterial genera with the greatest difference in abundance in the midgut of S. litura larvae and exhibited a negative correlation with each other. The root system of guava influenced the root structure, soil nutrients and the population structure and diversity of rhizosphere microorganisms by regulating the type and amount of root exudates. Root exudates also influenced the physiological and biochemical status of S. litura larvae by regulating the rhizosphere microorganisms driving the tritrophic interaction of plant-microbes-insects. Based on our results and the observed differences in pest occurrence among different grafted plants, improving varieties through grafting may become an effective strategy to reduce the impact of insect pests on guava.

Systemic lupus erythematosus (SLE) has been associated with gut microbiota in some studies. There is no clear evidence that cytokines act as mediators.

We first assessed the differences in gut microbiota between SLE patients and healthy controls using 16S rDNA sequencing. Subsequently, we used the summary statistics of gut microbiota, cytokines, and SLE from large genome-wide association studies. To explore the causal relationships between gut microbiota and SLE and identify potential mediating cytokines, we performed bidirectional Mendelian randomization analyses. Finally, the levels of potentially mediating cytokines were determined by ELISA.

Fecal 16S rDNA sequencing showed that there was gut microbiota disorder in SLE patients. Based on two-sample analysis, seven gut microbiota taxa were causally associated with SLE. SLE influenced the relative abundance of two gut microbiota taxa in our large-scale MR study. Mediation analyses revealed that the causal relationship between genus Lachnospiraceae UCG001 and SLE was exclusively mediated by fibroblast growth factor 19 (FGF19) levels and the causal relationship between order Lactobacillales and SLE was exclusively mediated by tumor necrosis factor receptor superfamily member 9 (TNFRSF9) levels. Elevated levels of FGF19 affected the association between the reduced relative abundance of the genus Coprobacter and SLE, mediating by a proportion of 10.64% (P = 0.030). Furthermore, ELISA showed that circulating TNFRSF9 and FGF19 levels were higher in SLE patients than healthy controls.

Our study demonstrated that there is a causal link between some gut microbiota taxa and SLE. In addition, we revealed possible mediating effects in this relationship. Key Points • We first demonstrate a causal association between gut microbiota, cytokines, and SLE comprehensively. • Our experiments also confirmed that TNFRSF9 and FGF19 may play a role in SLE. These results provide new ideas for microbiome-based investigation of new mechanisms and therapies for SLE.

Immune-mediated skin disorders arise from dysfunctional immune responses, instigating inflammatory dermatoses and a reduced quality of life. The complex pathogenesis likely involves genetic risks, environmental triggers and aberrant immune activation. An emerging body of evidence suggests that bile acid disturbances may critically promote immune pathology in certain skin conditions. Bile acids synthesised from cholesterol regulate nutrient metabolism and immune cell function via nuclear receptors and G protein-coupled receptors (GPCRs). Altered bile acid profiles and receptor expression have been identified in psoriasis, atopic dermatitis (AD) and autoimmune blistering diseases. Disruptions in bile acid signalling affect the inflammatory and metabolic pathways linked to these disorders. Targeting components of the bile acid axis represents a promising therapeutic strategy. This review elucidates the intricate links between bile acid homeostasis and immune dysfunction in inflammatory skin diseases, synthesising evidence that targeting bile acid pathways may unlock innovative therapeutic avenues. This study compiles clinical and experimental data revealing disrupted bile acid signalling and composition in various immune-mediated dermatoses, highlighting the emerging significance of bile acids in cutaneous immune regulation.

While growing evidence highlights the role of gut microbiota and inflammatory proteins in cancer, with cancer-related inflammation now considered the seventh hallmark of cancer, the direct causal relationships between specific microbiota, cancer, and the potential mediating effects of inflammatory proteins have not been fully established.

We employed Mendelian randomization (MR) to assess the causal relationships between gut microbiota, inflammatory proteins, and eighteen distinct cancers using data from extensive genome-wide association studies (GWAS). The primary statistical method utilized was inverse variance weighting (IVW). We also investigated whether inflammatory proteins could mediate the effects of gut microbiota on cancer development.

Our findings revealed 42 positive and 49 inverse causal impacts of gut microbiota on cancer risk (P < 0.05). Additionally, we identified 32 positive and 28 inverse causal relationships between inflammatory proteins and cancer risk. Moreover, genus Collinsella decreased the risk of lung cancer by decreasing levels of T-cell surface glycoprotein CD5 (mediating effect = 16.667%), while genus Ruminococcaceae UCG005 increased the risk of mesothelioma by increasing levels of CCL4 (mediating effect = 5.134%).

Our study provides evidence for a causal association between gut microbiota, inflammatory proteins, and eighteen different cancer types. Notably, the T-cell surface glycoprotein CD5 and CCL4 were identified as mediators linking the genus Collinsella with lung cancer and the genus Ruminococcaceae UCG005 with mesothelioma, respectively.

Although evolutionary medicine has produced several novel insights for explaining prevalent health issues, it has yet to sufficiently address possible adverse mental health effects of humans during long-term space missions While evolutionary applications to medicine have increased over the past 20 years, there is scope for the integration of evolutionary applications in the new branch of space medicine called bioastronautics, which analyses the effects on human bodies when in outer space. Evolutionary principles may explain what kinds of space environments increase mental health risks to astronauts, both in the short and long term; secondly, evolutionary principles may provide a more informed understanding of the evolutionary mismatch between terrestrial and space environments in which astronauts exist. This information may assist in developing frameworks for improving mental health of astronauts and future space colonists. Consequently, this paper will focus on some of the major evolutionary mismatches currently confronting astronauts' mental health, with an aim to improve medical knowledge. It will also provide possible therapeutic countermeasures based on evolutionary principles for reducing adverse mental effects on astronauts.

Background/Objectives: Infertility is a multifactorial condition influenced by various factors, including dysbiosis and alterations in the genital tract microbiome. Recent studies emphasize the microbiome's significant role in influencing a woman's fertility potential, thereby affecting the chances of spontaneous conception and the outcomes of assisted reproductive treatments. Understanding the microbial characteristics and unique features of a healthy genital microbiome, as well as how changes in its composition can impact fertility, would allow for a more comprehensive and personalized approach to managing assisted reproductive treatments. The microbiome also influences pregnancy outcomes, and restoring its balance has been shown to improve fertility in infertile couples. The human microbiome plays a key role in maintaining the body's overall health. Disruptions in microbiome balance among women of reproductive age can contribute to a range of pregnancy-related complications, with notable consequences for both maternal and fetal well-being. Emerging research has highlighted a connection between the reproductive tract microbiome and outcomes of assisted reproductive technologies (ART), suggesting that re-establishing a healthy microbial environment may enhance fertility in couples facing infertility. Methods: We conducted a search on PubMed using the keywords "microbiome", "infertility", and "ART" over the past 10 years. This article aims to provide an updated overview of the role of the microbiome in female reproductive health, with a focus on its implications for fertility treatment. Results: The microbiome has a significant role in influencing women's fertility. Conclusions: Understanding the microbiome's impact on fertility and pregnancy outcomes may lead to more effective and personalized approaches in fertility treatments, improving the chances of successful conception and pregnancy.

As a significant mental health disorder worldwide, the treatment of depression has long faced the challenges of a low treatment rate, significant drug side effects and a high relapse rate. Recent studies have revealed that the gut microbiota and neuronal mitochondrial dysfunction play central roles in the pathogenesis of depression: the gut microbiota influences the course of depression through multiple pathways, including immune regulation, HPA axis modulation and neurotransmitter metabolism. Mitochondrial function serves as a key hub that mediates mood disorders through mechanisms such as defective energy metabolism, impaired neuroplasticity and amplified neuroinflammation. Notably, a bidirectional regulatory network exists between the gut microbiota and mitochondria: the flora metabolite butyrate enhances mitochondrial biosynthesis through activation of the AMPK-PGC1α pathway, whereas reactive oxygen species produced by mitochondria counteract the flora composition by altering the intestinal epithelial microenvironment. In this study, we systematically revealed the potential pathways by which the gut microbiota improves neuronal mitochondrial function by regulating neurotransmitter synthesis, mitochondrial autophagy, and oxidative stress homeostasis and proposed the integration of probiotic supplementation, dietary fiber intervention, and fecal microbial transplantation to remodel the flora-mitochondrial axis, which provides a theoretical basis for the development of novel antidepressant therapies targeting gut-brain interactions.

Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD pathogenesis and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.

Background: Previous studies have demonstrated that the gut microbiota (GM) and rheumatoid arthritis (RA) are significantly associated, but the causal relationship has not been fully elucidated. Methods: We investigated the association between GM and RA using Mendelian randomization (MR) with two independent samples. Our study aimed to determine the causal relationship between gut microbiota and RA, including its seronegative and seropositive subtypes. Using data from a genome-wide association study (GWAS), we identified instrumental variables for 211 gut bacteria types. We then analyzed the FinnGen GWAS dataset, which included 3877 seronegative RA cases and 285,035 controls, along with 4290 seropositive RA cases and 368,362 controls, employing the inverse variance weighted (IVW) method and rigorous tests for pleiotropy and heterogeneity to ensure reliability. Results: The IVW results revealed that Prevotella 9, Sutterella, and Christensenellaceae R.7 exhibited an adverse correlation with seronegative RA (p < 0.05). Additionally, Lachnospira, Slackia, Roseburia, Barnesiella, and Prevotella 7 were associated with a reduced occurrence of seropositive RA (p < 0.05). Conversely, Ruminococcaceae UCG002 and Ruminococcus gauvreauii were linked to an increased susceptibility to seropositive RA (p < 0.05). Notably, no significant heterogeneity (p > 0.05) or pleiotropy (p > 0.05) was detected in the analysis of the significant MR estimates. Conclusions: Our study suggested significant associations between several gut bacteria and RA subtypes, indicating a potential microbial influence on RA development. These findings enhance our understanding of the gut-joint axis in RA and highlight promising targets for future microbiota-based therapies.

The gut-liver axis is essential in animal disease and health. However, the role of the gut-liver axis in the anti-disease mechanism of disease-resistant grass carp (DRGC) derived from the backcross of female gynogenetic grass carp (GGC) and male grass carp (GC) remains unclear. This study analyzed the changes in gut histopathology, fecal intestinal microflora and metabolites, and liver transcriptome between GC and DRGC. Histological analysis revealed significant differences in the gut between DRGC and GC. In addition, microbial community analyses indicated that hybridization induced gut microbiome variation by significantly increasing the proportion of Firmicutes and Bacteroidota in DRGC. Metabolomic data revealed that the hybridization-induced metabolic change was probably characterized by being related to taurocholate and sphinganine in DRGC. Transcriptome analysis suggested that the enhanced disease resistance of DRGC was primarily attributed to immune-related genes (SHMT2, GOT1, ACACA, DLAT, GPIA, TALDO1, G6PD, and FASN). Spearman's correlation analysis revealed a significant association between the gut microbiota, immune-related genes, and metabolites. Collectively, the gut-liver axis, through the interconnected microbiome-metabolite-gene pathway, may play a crucial role in the mechanism of greater disease resistance in DRGC, offering valuable insights for advancing the grass carp cultivation industry.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants known for their environmental persistence and bioaccumulation, posing significant health risks. This study examines the toxic effects of a representative PCBs (Aroclor 1254) on yellowfin seabream (Acanthopagrus latus) exposured for 30 days through a multi-omics approach. Histopathological examinations revealed structural damage to the intestinal structure and hepatic steatosis, along with elevated serum lipopolysaccharide levels, indicating compromised intestinal barrier integrity and liver inflammation. Metabolomic profiling showed significant alterations in lipid metabolites, including elevated lysophosphatidylcholines and arachidonic acid derivatives. Transcriptomic analysis unveiled 2272 differentially expressed genes in the liver, with notable changes in immune response and metabolic pathways. Gut microbiome analysis showed dysbiosis characterized by an increase in Proteobacteria and a decrease in Firmicutes and Actinobacteria. Remarkably, Tetranor-12S-HETE and LPC 15:1 emerged as key biomarkers for the disruption of the gut-liver axis, correlating with immune gene expression and gut microbiota composition. The integration of transcriptomic, metabolomic, and microbiome data highlighted the complex interplay between A1254 exposure and the gut-liver axis, emphasizing the central role played by PPAR signaling in mediating these effects. Collectively, these results indicate that exposure to A1254 results in bioaccumulation in the liver and gut, leading to severe tissue injury, microbiota dysbiosis, and dysregulation of the gut-liver axis, ultimately disrupting lipid metabolism. These findings underscore the metabolic health risks posed by PCBs exposure in aquatic environments.

Psychiatric disorders pose substantial global burdens on public health, yet therapeutic options remain limited. Recently, gut microbiota is in the spotlight of new research on psychiatric disorders, as emerging discoveries have highlighted the importance of gut microbiome in the regulation of central nervous system via mediating the gut-brain-axis bidirectional communication. While metagenomics studies have accumulated for psychiatric disorders, few systematic efforts were dedicated to integrating these high-throughput data across diverse phenotypes, interventions, geographical regions, and biological species. To present a panoramic view of global data and provide a comprehensive resource for investigating the gut microbiota dysbiosis in psychiatric disorders, we developed the PsycGM, a manually curated and well-annotated database that provides the literature-supported associations between gut microbiota and psychiatric disorders or intervention measures. In total, PsycGM incorporated 559 studies from 31 countries worldwide, encompassing research involving humans, rats, mice, and non-human primates. PsycGM documented 8907 curated associations between 1514 gut microbial taxa and 11 psychiatric disorders, as well as 4050 associations between 869 taxa and 232 microbiota-based and non-microbiota-based interventions. Moreover, PsycGM provided a user-friendly web interface with comprehensive information, enabling browsing, retrieving and downloading of all entries. In the application of PsycGM, we panoramically depicted the intestinal microecological imbalance in depression. Additionally, we identified 9 microbial taxa consistently altered in patients with depression, with the most common dysregulations observed for Parabacteroides, Alistipes, and Faecalibacterium; in animal models of depression, consistent changes were observed in 21 microbial taxa, most frequently reported as Helicobacter, Lactobacillus, Roseburia, and the ratio of Firmicutes/Bacteroidetes. PsycGM is a comprehensive resource for future investigations on the role of gut microbiota in mental and brain health, and for therapeutic target innovations based on modifications of gut microbiota. PsycGM is freely accessed at http://psycgmomics.info .

The microbiota, a complex assembly of microorganisms residing in various body systems, including the gastrointestinal tract, plays a crucial role in influencing various physiological processes in the human body. The dynamic nature of gut microbiota is especially pronounced in children and is influenced by factors like breastfeeding and antibiotic use. Dysbiosis, characterized by alterations in microbiota composition or function, is associated with several pediatric endocrine disorders, such as precocious puberty, polycystic ovarian syndrome, and diabetes mellitus. This review focuses on the intricate relationship between gut microbiota and the pediatric endocrine system. The aim of this narrative review is to critically examine the existing literature to elucidate the impact of gut microbiota on the pediatric endocrine system and associated disorders. Additionally, potential interventions, such as probiotics and current gaps in knowledge, will be discussed. Despite emerging treatments like probiotics, further research is needed to understand and validate their effectiveness in treating pediatric endocrine disorders associated with dysbiosis.

Density is an important aquaculture parameter. When the pearl gentian grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) is farmed intensively, it could lead to a degradation in genetic resources and an increase in disease outbreaks. The composition of the intestinal microbiota plays a key role in creating a specific intestinal microecosystem, which is essential for the survival, growth, and immune response of the host under environmental stress like overcrowding. This study utilized 16S rRNA sequencing and metabolomics analysis techniques to investigate the differences in intestinal microbial community stability of grouper under different stocking time and density pressure conditions. The research results showed that compared to the low-density group, the high-density group of groupers experienced an increase in mortality rate and feed coefficient in the early stages of culture, while the weight gain rate decreased. Differential analysis of intestinal microbial communities revealed significant differences in the gut microbiota of grouper between different density groups after 10 days of culture, but no significant differences were observed after 20 days of culture. At the same time, intestinal histopathology showed that the high-density group of groupers exhibited a reduction in intestinal villi length and thickness of the intestinal wall after 10 days of culture. However, the intergroup differences had reduced after 20 days of culture. Furthermore, high density cultivation upregulated the expression of inflammatory factors like IL-1β, TNF-α, IL-8, and IL-6 in the intestinal tract of groupers after 10 days of culture. However, after 20 days of culture, the expression levels of intestinal inflammatory factors in both the high-density and low-density groups of groupers were significantly reduced, and the differences between the intergroup diminished. Through correlation analysis of differential metabolites and species in the intestine, multiple metabolites significantly upregulated and associated with the upregulation of the Staphylococcus genus were identified in the intestinal tract of groupers after 20 days of high-density cultivation. The selected four associated metabolites (including creatine, fosinopril, 4-aminobutyric acid, and guanidinopropanoic acid) were validated to significantly reduce the expression of cellular inflammatory factors using the self-established grouper head kidney (HK) cell line. In conclusion, density pressure in the early culture period could affect the stability of the intestinal microbial environment of grouper. As aquaculture time increases, the intestinal microbial community of grouper drives the body's anti-inflammatory response and enhanced its adaptation to density pressure by regulating own structure and secretion of metabolites.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

The traditional view of sterile urine has been challenged by advancements in next-generation sequencing, revealing that the urinary microbiome significantly influences individual health and various urinary system diseases. Urinary tract infections in patients with neurogenic bladder are highly prevalent, recurrent, and lifelong. If frequent urinary tract infections are not adequately managed, they may ultimately lead to chronic renal failure. The excessive use of antibiotics to prevent and treat urinary tract infections may lead to increased bacterial resistance, limiting future therapeutic options. This review summarizes commonly used microbiome research techniques and urine collection methods, compiles current studies on the urinary microbiome in neurogenic bladder patients, and discusses the potential implications of urinary microbiome composition for preventing, diagnosing, and treating urinary tract infections. By summarizing current research findings, we aim to enhance understanding of the urinary microbiome in neurogenic bladder patients and promote the standardization and clinical translation of microbiome research.

The interplay between nutrition and infectious diseases has been a central theme in health sciences for the last decades due to its great impact on the pediatric population, especially in immunocompromised patients and critically ill children. As conventional treatment and the development of antimicrobials for most infections standard treatment is either limited or not possible, alternative treatment options should be explored. Recent research shows that early enteral nutrition and nutritional supplements (such as probiotics and symbiotics) could have a pivotal role in promoting a healthy microbiome and subsequently preventing and improving outcomes for certain pediatric infectious diseases. However, understanding the specific mechanism of action and tailoring nutritional interventions remains a significant challenge. The optimal dose range for different probiotic strains and prebiotics and the most effective combination for each treatment indication needs further investigation and is yet to be defined. Additionally, in the era of personalized medicine, goal- and patient-directed treatment are key to optimizing and improving outcomes and minimizing potential complications and side effects, especially in complex and immunocompromised patients. The main objectives of this narrative review are 1. to explore the relationship and the complex interactions between microbiota and the human immune system; 2. to describe the influence of nutrition on infectious diseases; 3. to evaluate the impact of supplementation with probiotics and symbiotics in the prevention and treatment of the most relevant infections in children; and 4. to identify knowledge gaps and potential research priorities regarding the use of these supplements in pediatric patients.

Background/Objectives: Anthocyanins (ACNs) derived from mulberry (Morus alba L.) exhibit potent antioxidant and anti-inflammatory activities. However, their low stability and bioavailability in physiological environments limit their therapeutic potential. This study aimed to enhance the stability and controlled release ACNs using a hot-melt extrusion drug delivery system (HME-DDS) formulation, HME-MUL-F2, and evaluate its effects on gut barrier function and microbiota composition in a DSS-induced colitis model. Methods: The anthocyanin content of HME-MUL-F2 was quantified and compared with that of raw mulberry extract. The formulation's protective effects were assessed in Caco-2 and RAW 264.7 cells, confirming its biocompatibility and anti-inflammatory properties. The therapeutic efficacy was further evaluated in a dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) model, focusing on gut barrier integrity, inflammatory cytokine modulation, and gut microbiota composition. Results: HME-MUL-F2 significantly improved gut barrier function by upregulating tight junction proteins and reducing inflammatory cytokine levels in the colitis model. Moreover, the formulation modulated gut microbiota composition, promoting beneficial bacteria while suppressing pathogenic strains. HME-MUL-F2 administration led to a significant increase in the Bacteroidetes-to-Firmicutes ratio, which is associated with improved gut health. These results indicate that HME-MUL-F2 significantly enhances anthocyanin bioavailability, leading to improved gut health and potential therapeutic applications for inflammatory conditions. Conclusions: This study highlights the potential of HME technology for improving the stability, bioavailability, and therapeutic efficacy of anthocyanins. HME-MUL-F2 is a sustained-release formulation that enhances gut barrier function and modulates intestinal microbial balance in a DSS-induced inflammatory bowel disease model. These findings strongly suggest that the observed therapeutic effects of HME-MUL-F2 are primarily due to enhanced anthocyanin bioavailability and targeted delivery to the colon, although further clinical studies will provide more definitive confirmation.

Recent advancements in multi-omics technologies have provided unprecedented opportunities to identify biomarkers associated with prediabetes, offering novel insights into its diagnosis and management. This review synthesizes the latest findings on prediabetes from multiple omics domains, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and radiomics. We explore how these technologies elucidate the molecular and cellular mechanisms underlying prediabetes and analyze potential biomarkers with predictive value in disease progression. Integrating multi-omics data helps address the limitations of traditional diagnostic methods, enabling early detection, personalized interventions, and improved patient outcomes. However, challenges such as data integration, standardization, and clinical validation and translation remain to be resolved. Future research leveraging artificial intelligence and machine learning is expected to further enhance the predictive power of multi-omics technologies, contributing to the precision diagnosis and tailored management of prediabetes.

The intestinal microbiota has major influence on human physiology and modulates health and disease. Complex host-microbe interactions regulate various homeostatic processes, including metabolism and immune function, while disturbances in microbiota composition (dysbiosis) are associated with a plethora of human diseases and are believed to modulate disease initiation, progression and therapy response. The vast complexity of the human microbiota and its metabolic output represents a great challenge in unraveling the molecular basis of host-microbe interactions in specific physiological contexts. To increase our understanding of these interactions, functional microbiota research using animal models in a reductionistic setting are essential. In the dynamic landscape of gut microbiota research, the use of germ-free and gnotobiotic mouse technology, in which causal disease-driving mechanisms can be dissected, represents a pivotal investigative tool for functional microbiota research in health and disease, in which causal disease-driving mechanisms can be dissected. A better understanding of the health-modulating functions of the microbiota opens perspectives for improved therapies in many diseases. In this review, we discuss practical considerations for the design and execution of germ-free and gnotobiotic experiments, including considerations around germ-free rederivation and housing conditions, route and timing of microbial administration, and dosing protocols. This comprehensive overview aims to provide researchers with valuable insights for improved experimental design in the field of functional microbiota research.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.

Condomless receptive anal intercourse stands out as the sexual practice with highest risk of HIV-1 infection. Recent studies have suggested that the gut microbiome influences susceptibility to HIV transmission. This review explores recent research on host risk factors, the rectal microbiome composition, local inflammation, and bacteria-derived mediators that may affect HIV transmission.

Constitutive host factors such as rectal mucosal structure and immune cell populations in the rectum contribute to increased susceptibility. Changes in the composition of the rectal microbiota, influenced by sexual practices and HIV infection modulate immune activation and inflammation, impacting HIV susceptibility. Bacteria-derived mediators may further influence immune responses and HIV replication in the rectal mucosa.

Understanding the role of the rectal microbiome in HIV transmission has important clinical implications. Targeted interventions that modulate the microbiome may reduce susceptibility to HIV transmission by regulating immune responses and inflammation. Further research into the host-microbiome interactions could lead to novel preventive and therapeutic strategies to mitigate HIV transmission.

As a significant cause of global mortality, the cancer has also economic impacts. In the era of cancer therapy, mitigating side effects and costs and overcoming drug resistance is crucial. Microbial species can grow inside the tumor microenvironment and inhibit cancer growth through direct killing of tumor cells and immunoregulatory effects. Although microbiota or their products have demonstrated anticancer effects, the possibility of acting as pathogens and exerting side effects in certain individuals is a risk. Hence, several genetically modified/engineered bacteria (GEB) have been developed to this aim with ability of diagnosing and selective targeting and destruction of cancers. Additionally, GEB are expected to be considerably more efficient, safer, more permeable, less costly, and less invasive theranostic approaches compared to wild types. Potential GEB strains such as Escherichia coli (Nissle 1917, and MG1655), Salmonella typhimurium YB1 SL7207 (aroA gene deletion), VNP20009 (∆msbB/∆purI) and ΔppGpp (PTet and PBAD), and Listeria monocytogenes Lmat-LLO have been developed to combat cancer cells. When used in tandem with conventional treatments, GEB substantially improve the efficacy of anticancer therapy outcomes. In addition, public acceptance, optimal timing (s), duration (s), dose (s), and strains identification, interactions with other strains and the host cells, efficacy, safety and quality, and potential risks and ethical dilemmas include major challenges.

Dietary polyphenols are garnering attention in the scientific community due to their potential health-beneficial properties and preventative effects against chronic diseases, viz. cardiovascular diseases, diabetes, obesity, and neurodegenerative diseases. Polyphenols are antioxidants that change microbial composition by suppressing pathogenic bacteria and stimulating beneficial bacteria. The interaction of polyphenols with dietary fibers affects their bioaccessibility in the upper and lower parts of the digestive tract. Dietary fibers, polyphenols, their conjugates, and their metabolites modulate microbiome population and diversity. Consuming polyphenol-rich dietary fibers such as pomegranate, cranberry, berries, and tea improves gut health. A complex relationship exists between polyphenol-rich diets and gut microbiota for functioning in human health. In this review, we provide an overview of the interactions of dietary polyphenols, fibers, and gut microbiota, improving the understanding of the functional properties of dietary polyphenols.

Inflammatory Bowel Disease (IBD) is increasing worldwide and has become a global emergent disease. Probiotics have been reported to be effective in relieving colitis. Previous studies found ripened Pu-erh tea (RPT) promoted gut microbiota resilience against dextran sulfate sodium (DSS)-induced colitis in mice by increasing relative abundance of Lactobacillus. However, whether and how it alleviated DSS-induced colitis in mice need to be explored. Here, we screened a probiotic Lactobacillus johnsonii GLJ001 from feces of ripened Pu-erh tea (RPT)-administrated mice. In this study, L. johnsonii GLJ001 attenuated symptoms of DSS-induced colitis in mice, including weight loss, increased disease activity index (DAI), colon shortening and colon tissue damage, as well as high expression of inflammatory cytokines and disturbances of intestine barrier function. Furthermore, abundances of short-chain fatty acids (SCFAs)-producing bacteria (i.e. Clostridium cluster IV and XIVa, Lachnospiracea_incertae_sedis and Ruminococcus) were enhanced in the cecum of mice treated with L. johnsonii GLJ001, accompanying by an increase of SCFAs. It was also found that SCFAs inhibited mRNA expression of M1 macrophage markers (Inos and CD86), inflammatory cytokines (TNF-α and Il-1β) and SCFAs receptors (Gpr41 and Gpr43) induced by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in THP-1 cell line. Collectively, L. johnsonii GLJ001 prevented DSS-induced colitis in mice by inhibiting M1 macrophage polarization via gut microbiota-SCFAs axis, and can be administered for management of colitis.

Several studies have suggested that probiotics could play a role in the management of patients with chronic bacterial prostatitis (CBP). In this randomized, placebo-controlled clinical study, we evaluated the efficacy and safety of consumption of probiotics containing human Lactobacillus casei DG® as an add-on treatment in patients with clinical recurrences of CBP, through gut microbiota modification analysis. Enrolled patients with CBP were randomized to receive for 3 months probiotics containing human Lactobacillus casei DG® or placebo following 1 month treatment with ciprofloxacin. During the enrollment and follow-ups, urological examinations analyzed symptoms and quality of life, while microbiological tests analyzed gut and seminal microbiota. During the study, the development of adverse drug reactions was evaluated through the Naranjo scale. Twenty-four patients with CBP were recruited and treated for 3 months with placebo (n. 12) or with Lactobacillus casei DG® (n. 12). Lactobacillus casei DG® induced a significantly (p < 0.01) faster recovery of symptoms than placebo (2 days vs. 8 days) and an increased time free from symptoms (86 days vs. 42 days) without the occurrence of adverse events. In the probiotic group, the appearance of Lactobacilli after 30 days (T1) was higher vs. the placebo group, and a significant reduction in Corynebacterium, Peptoniphilus, Pseudomonas, Veillonella, Staphylococcus, and Streptococcus was also observed. These preliminary data suggest that in patients with CBP, the use of Lactobacillus casei DG after an antimicrobial treatment improves the days free of symptoms and the quality of life, without the development of adverse drug reactions.

While Drosophila melanogaster serves as a crucial model for investigating both the circadian clock and gut microbiome, our understanding of their relationship in this organism is still limited. Recent analyses suggested that the Drosophila gut microbiome modulates the host circadian transcriptome to minimize rapid oscillations in response to changing environments. Here, we examined the composition and abundance of the gut microbiota in wild-type and arrhythmic per01 flies, under 12 h:12 h light: dark (12:12 LD) and constant darkness (DD) conditions. The gut microbiota of wild-type and per01 flies showed differences in composition, suggesting that the D. melanogaster circadian gene per has a role in shaping the gut microbiome. In 12:12 LD and DD conditions, per01 mutants showed significant daily variations in gut bacterial quantity, unlike wild-type flies. This suggests that per is involved in maintaining the daily stability of gut microbiome load in D. melanogaster. Expanding these analyses to other fly strains with disrupted circadian clocks will clarify whether these effects originate from a circadian function of per or from its possible pleiotropic effects. Finally, some gut bacteria exhibited significant 24 h fluctuations in their relative abundance, which appeared independent from the fly circadian clock, suggesting that certain gut commensal bacteria in Drosophila may possess a host-independent circadian clock.

Growing evidence suggests that the gut-brain axis influences brain function, particularly the role of intestinal microbiota in modulating cognitive processes. Probiotics may alter brain function and behavior by modulating gut microbiota, with implications for neurodegenerative diseases like Alzheimer's disease (AD). The purpose of this review is to systematically review the current literature exploring the effects of probiotic supplementation on gut microbiota and cognitive function in AD and mild cognitive impairment (MCI).

A comprehensive literature search was conducted across PubMed/Medline, Embase, and Scopus to identify relevant randomized controlled trials (RCTs) from inception to 20 August 2024. The search focused on comparing outcomes between intervention and control/placebo groups. Data searches, article selection, data extraction, and risk of bias assessment were performed in accordance with Cochrane guidelines.

PROSPERO registration no: CRD42023446796.

Data from four RCTs involving 293 Individuals (AD and MCI patients) receiving mainly Lactobacillus and Bifidobacterium strains showed some beneficial effects on cognitive function, altered gut microbiota composition, and positively affected metabolic biomarkers. However, variability in microbiota assessment across studies limits the interpretation of results. The limited number and quality of the existing studies make it difficult to draw definitive conclusions from the data. Additional high-quality research is clearly needed.

Probiotics show promise as an adjunctive intervention for cognitive decline, but larger, long-term trials are needed to confirm their efficacy and clinical applicability in neurodegenerative diseases like AD.

The human bowel is exposed to numerous biotic and abiotic external noxious agents. Accordingly, the digestive tract is frequently involved in malfunctions within the organism. Together with the commensal intestinal flora, it regulates the immunological balance between inflammatory defense processes and immune tolerance. Pathological changes in this system often cause chronic inflammatory bowel diseases including Crohn's disease and ulcerative colitis. This review article highlights the complex interaction between commensal microorganisms, the intestinal microbiome, and the intestinal epithelium-localized local immune system. The main functions of the human intestinal microbiome include (i) protection against pathogenic microbial colonization, (ii) maintenance of the barrier function of the intestinal epithelium, (iii) degradation and absorption of nutrients and (iv) active regulation of the intestinal immunity. The local intestinal immune system consists primarily of macrophages, antigen-presenting cells, and natural killer cells. These cells regulate the commensal intestinal microbiome and are in turn regulated by signaling factors of the epithelial cells and the microbiome. Deregulated immune responses play an important role and can lead to both reduced activity of the commensal microbiome and pathologically increased activity of harmful microorganisms. These aspects of chronic inflammatory bowel disease have become the focus of attention in recent years. It is therefore important to consider the immunological-microbial context in both the diagnosis and treatment of inflammatory bowel diseases. A promising holistic approach would include the most comprehensive possible diagnosis of the immune and microbiome status of the patient, both at the time of diagnostics and during therapy.

The human body constitutes a living environment for trillions of microorganisms, which establish the microbiome and, the largest population among them, reside within the gastrointestinal tract, establishing the gut microbiota. The term "gut microbiota" refers to a set of many microorganisms [mainly bacteria], which live symbiotically within the human host. The term "microbiome" means the collective genomic content of these microorganisms. The number of bacterial cells within the gut microbiota exceeds the host's cells; collectively and their genes quantitatively surpass the host's genes. Immense scientific research into the nature and function of the gut microbiota is unraveling its roles in certain human health activities such as metabolic, physiology, and immune activities and also in pathologic states and diseases. Interestingly, the microbiota, a dynamic ecosystem, inhabits a particular environment such as the human mouth or gut. Human microbiota can evolve and even adapt to the host's unique features such as eating habits, genetic makeup, underlying diseases, and even personalized habits. In the past decade, biologists and bioinformaticians have concentrated their research effort on the potential roles of the gut microbiome in the development of human diseases, particularly immune-mediated diseases and colorectal cancer, and have initiated the assessment of the impact of the gut microbiome on the host genome. In the present chapter, we focus on the biological features of gut microbiota, its physiology as a biological factory, and its impacts on the host's health and disease status.

The gut's symbiome, a hidden metabolic organ, has gained scientific interest for its crucial role in human health. Acting as a biochemical factory, the gut microbiome produces numerous small molecules that significantly impact host metabolism. Metabolic profiling facilitates the exploration of its influence on human health and disease through the symbiotic relationship. Fecal metabolomics-based analysis is an indisputably valuable tool for elucidating the biochemistry of digestion and absorption in the gastrointestinal system, serving as the most suitable specimen to study the symbiotic relationship between the host and the intestinal microbiota. It is well-established that the balance of the intestinal microbiota changes in response to various stimuli, both physiological, such as gender, age, diet, and exercise, and pathological, such as gastrointestinal and hepatic diseases. Fecal samples have been analyzed using widely adopted analytical techniques, including NMR spectroscopy, GC-MS, and LC-MS/MS. Rat fecal samples are frequently used and particularly useful substrates for metabolomics-based studies in related fields.The complexity and diversity of fecal samples necessitate careful and skillful handling to extract metabolites, while avoiding their deterioration, effectively and quantitatively. Several determinative factors, such as the fecal sample weight to extraction solvent solution volume, the nature and pH value of the extraction solvent, and the homogenization process, play crucial roles in achieving optimal extraction for obtaining high-quality metabolic fingerprints, whether for untargeted or targeted metabolomics.

Intestinal microbiota has profound effects on host health and adaptation to environmental changes. Bufo gargarizans and Rana chensinensis coexist in the same habitat and have been paid much attention to economically because of their medicinal value. To date, no comparison of differences between single and mixed populations has been made. In our study, differences in the structure and function of the intestinal microbial of B. gargarizans and R. chensinensis in environments of single-species and mixed-species growth were investigated by high-throughput sequencing. Our results suggest that the cogrowth of B. gargarizans and R. chensinensis could lead to the decrease of the abundance of pathogenic bacteria (Bosea) and the introduction or increase of beneficial bacteria (Kaistia, Cetobacterium and Erysipelatoclostridium). The Tax4Fun-based functional predictions revealed that the level of pathways involved in the metabolism of R. chensinensis in mixed-species aquaria is greatly up-regulated. This study provides useful information for ecologists, ecosystem policy makers and wildlife conservationists to promote more effective conservation measures.

The intricate Gut microbiome is evolving as an important system and is hypothesized to be a "metabolic organ" within the host. Alterations in Gut microbiota and inflammation associated with several diseases play a crucial role in drug transformation through microbiota-host co-metabolism, modified pharmacokinetic and pharmacodynamics profiles, and may result in the formation of toxic metabolites with interference in drug response. In recent studies, a large number of drugs are reported that are co-metabolized by the host and the Gut microbial enzymes. we summarize the direct and indirect involvement of Gut microbiome promotion or inhibition of cardiovascular diseases, mechanisms on bioavailability, and therapeutic outcomes of cardiovascular drugs, particularly pharmacokinetics and pharmacodynamics profiles in light of AUC, Tmax, Cmax, and bioavailability and drug transportation via immune cells, inter-individual variations in intestinal microbial taxonomy, influence of drugs on diversity and richness of microflora, high lightening limitations and significance of in personalized medicine. Recent advances in target-drug delivery by nanoparticles with limitations and challenges in application are discussed. The cross-talk between Gut microbiota and cardiovascular drugs signifies a better understanding and rationale for targeting the Gut microbiota to improve the therapeutic outcome for cardiovascular diseases, with present-day limitations.

The substitution of fishmeal with high-level soybean meal in the diet of crustaceans usually induces lipid accumulation and oxidative stress in the hepatopancreas. Therefore, it is essential to alleviate these adverse effects. In the present study, SBPs were used to alleviate the negative effects of a fishmeal decrease on the growth performance, lipid metabolism, antioxidant capacity, and gut microbiota of oriental river prawn (Macrobrachium nipponense) in an 8-week feeding trial. Three isonitrogenic and isolipidic diets were prepared as follows: R (reference diet with 32% fishmeal), CT (control diet with 22% fishmeal), and SBP (22% fishmeal with 1.25 g/kg soybean bioactive peptides). The prawns (initial biomass per tank 17 g) were randomly divided into three groups with four replicates. The results showed that the low-fishmeal diet induced the following: (1) the inhibition of growth performance and survival of prawns; (2) an increase in triglyceride content in the hepatopancreas and hemolymph and downregulation of carnitine palmitoyl transferase 1 (cpt1) gene expression; (3) a reduction in antioxidant enzymes' activities and their genes expression levels and an increase malondialdehyde (MDA) content; and (4) an increase in the abundance of the conditional pathogen Pseudomonas in the gut. SBPs supplementation in the CT diet effectively alleviated most of the above adverse effects. SBPs enhanced inducible nitric oxide synthase (iNOS) activity to synthesize nitric oxide (NO) by activating the imd-relish pathway. Most importantly, SBPs increased the potential probiotic Rikenellaceae_RC9_gut_group abundance and decreased the abundance of the conditional pathogen Pseudomonas in the gut. In conclusion, SBPs supplementation can improve low-fishmeal-diet-induced growth inhibition by regulating the gut microbiota composition to ameliorate lipid deposition and oxidative stress and strengthen immune status in oriental river prawn.