Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials.

This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment.

Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.

The interplay between the gut microbiota and gastrointestinal hormones plays a pivotal role in the health of the host and the development of diseases. As a vital component of the intestinal microecosystem, the gut microbiota influences the synthesis and release of many gastrointestinal hormones through mechanisms such as modulating the intestinal environment, producing metabolites, impacting mucosal barriers, generating immune and inflammatory responses, and releasing neurotransmitters. Conversely, gastrointestinal hormones exert feedback regulation on the gut microbiota by modulating the intestinal environment, nutrient absorption and utilization, and the bacterial biological behavior and composition. The distributions of the gut microbiota and gastrointestinal hormones are anatomically intertwined, and close interactions between the gut microbiota and gastrointestinal hormones are crucial for maintaining gastrointestinal homeostasis. Interventions leveraging the interplay between the gut microbiota and gastrointestinal hormones have been employed in the clinical management of metabolic diseases and inflammatory bowel diseases, such as bariatric surgery and fecal microbiota transplantation, offering promising targets for the treatment of dysbiosis-related diseases.

Microbiome science has greatly expanded our understanding of the diverse composition and function of gut microorganisms over the past decades. With its rich microbial composition, the microbiome hosts numerous functionalities essential for metabolizing food ingredients and nutrients, resulting in the production of active metabolites that affect food fermentation or gut health. Most of these processes are mediated by microbial enzymes such as carbohydrate-active enzymes and amino acid metabolism enzymes. Metatranscriptomics enables the capture of active transcripts within the microbiome, providing invaluable functional insights into metabolic activities. Given the inter-kingdom complexity of the microbiome, metatranscriptomics could further elucidate the activities of fungi, archaea, and bacteriophages in the microbial ecosystem. Despite its potential, the application of metatranscriptomics in food and nutrition sciences remains limited but is growing. This review highlights the latest advances in food science (e.g., flavour formation and food enzymology) and nutrition science (e.g., dietary fibres, proteins, minerals, and probiotics), emphasizing the integration of metatranscriptomics with other technologies to address key research questions. Ultimately, metatranscriptomics represents a powerful tool for uncovering the microbiome activity, particularly in relation to active metabolic processes.

Post-stroke depression (PSD) is one of the most common and devastating neuropsychiatric complications in stroke patients, affecting more than one-third of survivors of ischemic stroke (IS). Despite its high incidence, PSD is often overlooked or undertreated in clinical practice, and effective preventive measures and therapeutic interventions remain limited. Although the exact mechanisms of PSD are not fully understood, emerging evidence suggests that the gut microbiota plays a key role in regulating gut-brain communication. This has sparked great interest in the relationship between the microbiota-gut-brain axis (MGBA) and PSD, especially in the context of cerebral ischemia. In addition to the gut microbiota, another important factor is the gut barrier, which acts as a frontline sensor distinguishing between beneficial and harmful microbes, regulating inflammatory responses and immunomodulation. Based on this, this paper proposes a new approach, the microbiota-immune-barrier axis, which is not only closely related to the pathophysiology of IS but may also play a critical role in the occurrence and progression of PSD. This review aims to systematically analyze how the gut microbiota affects the integrity and function of the barrier after IS through inflammatory responses and immunomodulation, leading to the production or exacerbation of depressive symptoms in the context of cerebral ischemia. In addition, we will explore existing technologies that can assess the MGBA and potential therapeutic strategies for PSD, with the hope of providing new insights for future research and clinical interventions.

Chicken gut microbiota plays an important role in maintaining their physiological health. However, the cultivability of chicken gut microbiota is not well understood, limiting the exploration of certain key gut bacteria in regulating intestinal health and nutritional metabolism. This study aimed to examine the cultivability of chicken cecal microbiota and to provide guidance for future chicken gut microbiota cultivation. A total of 58 different culture conditions were applied to culture broiler cecal microbiota, and the culture-dependent (CD; pooled colonies form each plate) and culture-independent (CI; broiler cecal contents) samples were collected for 16S rRNA gene sequencing and microbial analysis. The CD methods detected higher microbial richness (3,636 vs 2,331 OTUs) than CI methods, and the recovery rates of bacterial OTUs and genera reached 43.6% and 68.9%, respectively. The genera of Bacteroides (19.9%), Alistipes (11.0%) and Barnesiella (10.7%) were highly abundant detected by CI methods, however, there occupied a small proportion (<1.0%) of total cultured microbiota in CD methods. We then developed reference figures and tables showing optimal cultivation conditions for different gut bacteria taxa. Moreover, 81 different lactic acid bacteria strains covering 5 genera were isolated, and 15 strains had less than 97.0% similarity to known bacteria in the national center for biotechnology information (NCBI) online database. Overall, this study provides preliminary guidance in culturing specific gut microbiota from chickens, which will contribute to future studies to characterize the biological functions of key microbes in chicken nutritional metabolism and health.

Breast cancer is a widespread cancer with a high death rate globally. The incidence of breast cancer is expected to increase, particularly in low and middle-income countries due to environmental factors and lifestyle changes. Several risk factors, such as age, family history, hormonal and reproductive factors, have been identified to influence breast cancer development. Metabolic syndrome, is a metabolic disorder that has also been linked to breast cancer risk. The gut microbiome has been suggested as one of the environmental factors leading to breast cancer. The human microbiome is mainly colonized in the intestine by various bacterial species, including Lactobacillus, Bifidobacterium, and Streptococcus and protect the host against pathogenic microorganisms and regulate the immune system. This study included 50 female breast cancer patients and 50 healthy controls with matched ages. Stool fresh samples were taken from test and control groups and stored at - 20 °C until further investigations. DNA of the bacteria in stool samples was extracted using reverse transcription-quantitative polymerase chain reaction to check for the bacterial 16s rRNA gene. The exclusion criteria included other malignancies, recent intestinal surgery, infectious diarrhea, prolonged use of antibiotics, substance addiction, and pregnancy or lactation. Our findings exhibited that breast cancer patients had a higher incidence of metabolic syndrome (60%) compared to cancer-free controls (40%). Furthermore, breast cancer patients had significantly lower Bifidobacterium and Lactobacillus counts than the controls. No significant difference was found in Streptococcus counts between groups. These findings support the relationship between breast cancer and metabolic syndrome and suggest the potential involvement of Lactobacillus and Bifidobacterium in breast cancer pathophysiology. Our study supports the relation between breast cancer and disorder of metabolic syndrome and suggests the potential involvement of Lactobacillus and Bifidobacterium in breast cancer pathophysiology. Further research is necessary to investigate the complex interactions between genes, the environment, and the gut microbiome in breast cancer development. Understanding these interactions could lead to the progress of novel strategies for breast cancer prevention and treatment.

The gut microbiome, or the community of microorganisms residing in the gastrointestinal tract, has emerged as an important factor in breast cancer etiology and treatment. Specifically, the impact of gut bacterial populations on breast cancer therapeutic outcomes is an emerging area of research. The microbiota's role in modifying the pharmacokinetics of chemotherapy and endocrine-targeting therapies can alter drug efficacy and toxicity profiles. In addition, the gut microbiome's capacity to regulate systemic inflammation and immune responses may influence the effectiveness of both conventional and immunotherapeutic strategies for the treatment of breast cancer. Overall, while the bidirectional interactions between the gut microbiome and breast cancer therapies are still being studied, its impact is increasingly recognized. Future research may provide more definitive insights and help develop personalized therapeutic strategies to harness the microbiome to improve breast cancer treatment outcomes.

This study investigated the oral microbiome signatures associated with upper gastrointestinal (GI) and pancreaticobiliary cancers.

Saliva samples from cancer patients and age- and sex-matched healthy controls were analyzed using 16S rRNA-targeted sequencing, followed by comprehensive bioinformatics analysis.

Significant dissimilarities in microbial composition were observed between cancer patients and controls across esophageal cancer (EC), gastric cancer (GC), biliary tract cancer (BC), and pancreatic cancer (PC) groups (R2 = 0.067, = 0.075, = 0.068, and = 0.044; p = 0.001, = 0.001, = 0.002, and = 0.004, respectively). Additionally, the oral microbiome composition significantly differed by the four cancer sites (p = 0.001 for EC vs. GC, EC vs. BC, EC vs. PC, GC vs. BC, and GC vs. PC; p = 0.013 for BC vs. PC). We built oral metagenomic classifiers to predict cancer and selected specific microbial taxa with diagnostic properties. For EC, the classifier differentiated cancer patients and controls with good accuracy (area under the curve [AUC] = 0.791) and included three genera: Akkermansia, Escherichia-Shigella, and Subdoligranulum. For GC, the classifier exhibited high discriminative power (AUC = 0.961); it included five genera (Escherichia-Shigella, Gemella, Holdemanella, Actinomyces, and Stomatobaculum) and three species (Eubacterium sp. oral clone EI074, Ruminococcus sp. Marseille-P328, and Leptotrichia wadei F0279). However, microbial taxa with diagnostic features for BC and PC were not identified.

These findings suggested that the oral microbiome composition may serve as an indicator of tumorigenesis in upper GI and pancreaticobiliary cancers. The development of oral metagenomic classifiers for EC and GC demonstrates the potential value of microbial biomarkers in cancer screening.

In recent years, a growing body of research has highlighted the significant influence of the microbiota on tumor immunity within the tumor microenvironment (TME). While much attention has been given to bacteria, emerging evidence suggests that fungi also play crucial roles in tumor development. The present review aimed to consolidate the latest findings on the mechanisms governing the interactions between fungi and the immune system or TME. By elucidating these intricate mechanisms, novel insights into the modulation of tumor immunity and therapeutic strategies may be uncovered. Ultimately, a deeper understanding of the interplay between fungi and the TME holds promise for the development of innovative management strategies and targeted drugs to enhance tumor therapy efficacy.

The coal mine workplace environment is a significant factor in inducing occupational health issues, such as intestinal dysfunction in coal miners. However, the mechanism by which the coal mine workplace environment induces intestinal dysfunction is still unclear. Therefore, we applied the Coal Mine Workplace Environment Biological Simulation (CEBS) model which was previously constructed to detect the intestinal pathological manifestations and changes in the gut microbiota of mice from the perspectives of intestinal function, tissue morphology, and cell molecules. CEBS mice showed increased fecal water content, shortened colon length, significant activation of MPO+ and CD11b+ numbers, and significant changes in IL-1b, IL-6, and IL-12 expression levels. In addition, we also found an imbalance in the proportions of Firmicutes, Bacteroidetes, Lactobacillus, and Parabacteroides in CEBS mice, resulting in significant changes in gut microbial diversity. After intervention with compound probiotics, the intestinal function of CEBS + Mix mice was improved and inflammation levels were reduced. Results indicated that stress in the coal mine workplace environment can lead to intestinal dysfunction and inflammatory damage of the colon and use of compound probiotics can improve intestinal dysfunction in CBES mice. In our study, we revealed that there is a correlation between coal mine workplace environment and diversity disorders of gut microbiota. This discovery has enhanced the relevant theories on the causes of intestinal dysfunction in coal miners and has suggested a new approach to intervention.

The symbiotic gut microbiota is pivotal for human health, with its composition linked to various diseases and metabolic disorders. Despite its significance, there remains a gap in systematically evaluating how host phenotypes, such as gender, age, and body mass index (BMI), influence gut microbiota.

We conducted an analysis of the gut microbiota of 185 Chinese adults based on whole-metagenome shotgun sequencing of fecal samples. Our investigation focused on assessing the effects of gender, age, and BMI on gut microbiota across three levels: diversity, gene/phylogenetic composition, and functional composition. Our findings suggest that these phenotypes have a minor impact on shaping the gut microbiome compared to enterotypes, they do not correlate significantly within- or between-sample diversity. We identified a substantial number of phenotype-associated genes and metagenomic linkage groups (MLGs), indicating variations in gut microflora composition. Specifically, we observed a decline in beneficial Firmicutes microbes, such as Eubacterium, Roseburia, Faecalibacterium and Ruminococcus spp., in both older individuals and those with higher BMI, while potentially harmful microbes like Erysipelotrichaceae, Subdoligranulum and Streptococcus spp. increased with age. Additionally, Blautia and Dorea spp. were found to increase with BMI, aligning with prior research. Surprisingly, individuals who were older or overweight exhibited a lack of Bacteroidetes, a dominant phylum in the human gut microbiota that includes opportunistic pathogens, while certain species of the well-known probiotics Bifidobacterium were enriched in these groups, suggesting a complex interplay of these bacteria warranting further investigation. Regarding gender, several gender-associated MLGs from Bacteroides, Parabacteroides, Clostridium and Akkermansia were enriched in females. Functional analysis revealed a multitude of phenotype-associated KEGG orthologs (KOs).

Our study underscores the influence of gender, age, and BMI on gut metagenomes, affecting both phylogenetic and functional composition. However, further investigation is needed to elucidate the precise roles of these bacteria, including both pathogens and probiotics.

Evidence suggests that changes in the composition of gut microbiota may be linked to metabolic disorders including type 2 diabetes (T2D). The present study aims to evaluate the compositional changes of the intestinal microbiota in patients with T2D as compared to healthy individuals.

In this case-control study, there were 18 T2D patients and 18 healthy individuals who served as controls. To profile the gut microbiota in both groups, bacterial DNA was extracted from fecal samples and analyzed using quantitative real-time polymerase chain reaction (qPCR).

The study discovered that diabetics had significantly greater frequencies of the genus Bacteroides and the phylum Bacteroidetes than did controls (P = 0.03 and P < 0.001, respectively). Conversely, the Actinobacteria and Firmicutes phyla were significantly more abundant in the controls (P=0.01 for both). No significant differences were observed in the fecal populations of the genus Enterococcus, Clostridium clusters IV and XIVa, phylum Proteobacteria, and all bacteria between the studied groups (P=0.88, P=0.56, P=0.8, P=0.99, and P=0.7, respectively).

Our findings confirm that T2D may be associated with the gut microbiota fluctuations. These findings may be valuable for developing strategies to control or treatment T2D by restoring the intestinal microbiota through the strategic administration of specific probiotics/prebiotics and lifestyle and dietary modifications.

Bioactive peptides (BPs) are protein fragments with beneficial effects on metabolism, physiology, and diseases. This review focuses on proteolytic BPs, which are produced by the action of gut microbiota on proteins in food and have demonstrated to influence the composition of gut microbes. And gut microbiota are candidate targets of BPs to alleviate oxidative stress, enhance immunity, and control diseases, including diabetes, hypertension, obesity, cancer, and immune and neurodegenerative diseases. Despite promising results, further research is needed to understand the mechanisms underlying the interactions between BPs and gut microbes, and to identify and screen more BPs for industrial applications. Overall, BPs offer potential as therapeutic agents for various diseases through their interactions with gut microbes, highlighting the importance of continued research in this area.

Gut microbiota plays a crucial role in maintaining host homeostasis, impacting the progression and therapeutic outcomes of diseases, including inflammatory bowel disease, cancer, hepatic conditions, obesity, cardiovascular pathologies, and neurologic disorders, via immune, neural, and metabolic mechanisms. Hence, the gut microbiota is a promising target for disease therapy. The safety and precision of traditional microbiota regulation methods remain a challenge, which limits their widespread clinical application. This limitation has catalyzed a shift toward the development of multifunctional delivery systems that are predicated on microbiota modulation. Guided by bioinspired strategies, an extensive variety of naturally occurring materials and mechanisms have been emulated and harnessed for the construction of platforms aimed at the monitoring and modulation of gut microbiota. This review outlines the strategies and advantages of utilizing bioinspired principles in the design of gut microbiota intervention systems based on traditional regulation methods. Representative studies on the development of bioinspired therapeutic platforms are summarized, which are based on gut microbiota modulation to confer multiple pharmacological benefits for the synergistic management of diseases. The prospective avenues and inherent challenges associated with the adoption of bioinspired strategies in the refinement of gut microbiota modulation platforms are proposed to augment the efficacy of disease treatment.

The gastrointestinal (GI) tract harbors trillions of microorganisms known to influence human health and disease, and next-generation sequencing (NGS) now enables the in-depth analysis of their diversity and functions. Although a significant amount of research has been conducted on the GI microbiome, comprehensive metagenomic datasets covering the entire tract are scarce due to cost and technical challenges. Despite the widespread use of fecal samples, integrated datasets encompassing the entire digestive process, beginning at the mouth and ending with feces, are lacking. With this study, we aimed to fill this gap by analyzing the complete metagenome of the GI tract, providing insights into the dynamics of the microbiota and potential therapeutic avenues. In this study, we delved into the complex world of the GI microbiota, which we examined in five healthy Japanese subjects. While samples from the whole GI flora and fecal samples provided sufficient bacteria, samples obtained from the stomach and duodenum posed a challenge. Using a principal coordinate analysis (PCoA), clear clustering patterns were identified; these revealed significant diversity in the duodenum. Although this study was limited by its small sample size, the flora in the overall GI tract showed unwavering consistency, while the duodenum exhibited unprecedented phylogenetic diversity. A visual heat map illustrates the discrepancy in abundance, with Fusobacteria and Bacilli dominating the upper GI tract and Clostridia and Bacteroidia dominating the fecal samples. Negativicutes and Actinobacteria were found throughout the digestive tract. This study demonstrates that it is possible to continuously collect microbiome samples throughout the human digestive tract. These findings not only shed light on the complexity of GI microbiota but also provide a basis for future research.

Polycystic ovary syndrome (PCOS) is a multifaceted disease with an intricate etiology affecting reproductive-aged women. Despite attempts to unravel the pathophysiology, the molecular mechanism of PCOS remains unknown. There are no effective or suitable therapeutic strategies available to ameliorate PCOS; however, the symptoms can be managed. In recent years, a strong association has been found between the gut microbiome and PCOS, leading to the formulation of novel ideas on the genesis and pathological processes of PCOS. Further, gut microbiome dysbiosis involving microbial metabolites may trigger PCOS symptoms via many mechanistic pathways including those associated with carbohydrates, short-chain fatty acids, lipopolysaccharides, bile acids, and gut-brain axis. We present the mechanistic pathways of PCOS-related microbial metabolites and therapeutic opportunities available to treat PCOS, such as prebiotics, probiotics, and fecal microbiota therapy. In addition, the current review highlights the emerging treatment strategies available to alleviate the symptoms of PCOS.

Despite considerable advancements achieved using next-generation sequencing technologies in exploring microbial diversity, several species of the gut microbiome remain unknown. In this transformative era, culturomics has risen to prominence as a pivotal approach in unveiling realms of microbial diversity that were previously deemed inaccessible. Utilizing innovative strategies to optimize growth and culture medium composition, scientists have successfully cultured hard-to-cultivate microbes. This progress has fostered the discovery and understanding of elusive microbial entities, highlighting their essential role in human health and disease paradigms. In this review, we emphasize the importance of culturomics research on the gut microbiome and provide new theories and insights for expanding microbial diversity via the optimization of cultivation conditions.

The hair coat status of cattle serves as an easily observed indicator of economic value in livestock production; however, the underlying mechanism remains largely unknown. Therefore, the objective of the current study was to determine differences in the intestinal microbiota and metabolome of cattle based on a division of with either slick and shining (SHC) or rough and dull (MHC) hair coat in Simmental cows.

Eight SHC and eight MHC late-pregnancy Simmental cows (with similar parities, body weights, and body conditions) were selected based on their hair coat status, and blood samples (plasma) from coccygeal venipuncture and fecal samples from the rectum were collected. The intestinal microbiota (in the fecal samples) was characterized by employing 16S rRNA gene sequencing targeting the V3-V4 hypervariable region on the Illumina MiSeq PE300 platform, and plasma samples were subjected to LC-MS/MS-based metabolomics with Progenesis QI 2.3. Plasma macromolecular metabolites were examined for differences in the metabolism of lipids, proteins, mineral elements, and hormones.

Notable differences between the SHC and MHC groups related to host hair coat status were observed in the host metabolome and intestinal microbiota (P < 0.05). The host metabolome was enriched in histidine metabolism, cysteine and methionine metabolism, and purine metabolism in the SHC group, and the intestinal microbiota were also enriched in histidine metabolism (P < 0.05). In the MHC group, the symbiotic relationship transitioned from cooperation to competition in the MHC group, and an uncoupling effect was present in the microbe-metabolite association of intestine microbiota-host interactions. The hubs mediating the relationships between intestinal microbiota and plasma metabolites were the intestinal bacterial genus g__norank_f__Eubacterium_coprostanoligenes_group, plasma inosine, triiodothyronine, and phosphorus, which could be used to differentiate cows' hair coat status (P < 0.05).

Overall, the present study identified the relationships between the features of the intestinal microbiota and host hair coat status, thereby providing evidence and a new direction (intestine microbiota-host interplay) for future studies aimed at understanding the hair coat status of cattle.

It is becoming increasingly clear that the human microbiota, also known as "the hidden organ", possesses a pivotal role in numerous processes involved in maintaining the physiological functions of the host, such as nutrient extraction, biosynthesis of bioactive molecules, interplay with the immune, endocrine, and nervous systems, as well as resistance to the colonization of potential invading pathogens. In the last decade, the development of metagenomic approaches based on the sequencing of the bacterial 16s rRNA gene via Next Generation Sequencing, followed by whole genome sequencing via third generation sequencing technologies, has been one of the great advances in molecular biology, allowing a better profiling of the human microbiota composition and, hence, a deeper understanding of the importance of microbiota in the etiopathogenesis of different pathologies. In this scenario, it is of the utmost importance to comprehensively characterize the human microbiota in relation to disease pathogenesis, in order to develop novel potential treatment or preventive strategies by manipulating the microbiota. Therefore, this perspective will focus on the progress, challenges, and promises of the current and future technological approaches for microbiome profiling and analysis.

Three Gram-positive, obligately anaerobic bacterial strains, namely CSJ-1T, CSJ-3T, and CSJ-4T, were isolated from faeces of healthy persons. They were characterized through a combination of whole-genome sequencing, phenotypic traits, and metabolomic analysis. The genome sizes of CSJ-1T, CSJ-4T, and CSJ-3T were 3.3, 3.8, and 6.1 Mbp, with DNA G+C contents of 47.2, 48.3, and 48.8 mol%, respectively. Strain CSJ-3T was identified as representing a novel species, Diplocloster hominis (type strain CSJ-3T=CGMCC 1.18033T=JCM 36512T) of the genus Diplocloster. The 16S rRNA gene sequence similarity and whole genome average nucleotide identity (gANI) of CSJ-4T to its closest related species, Diplocloster modestus ASD 4241T, were 98.3 and 91.4 %, respectively. Comparative analysis of 16S rRNA gene sequences showed 91.6 % similarity between CSJ-1T and its closest phylogenetic neighbour, Catenibacillus scindens DSM 106146T, and 93.3 % similarity between CSJ-4T and its closest relative strain, Clostridium fessum SNUG30386T. Based on the polyphasic taxonomic results, we proposed two novel genera and three novel species. Strain CSJ-1T was identified as representing a novel species of novel genus, Anaerolentibacter hominis gen. nov. sp. nov. (type strain CSJ-1T=CGMCC 1.18046T=JCM 36511T) of the family Lachnospiraceae, and strain CSJ-4T was identified as representing a novel species of novel genus Pilosibacter fragilis gen. nov. sp. nov. (type strain CSJ-4T=CGMCC 1.18026T= JCM 36513T) of the family Clostridiaceae.

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

Different dietary interventions, especially intermittent fasting, are widely used and promoted by physicians; these regimens have been studied lately for their impact on the gut microbiota composition/function and, consequently, on the general physiopathological processes of the host. Studies are showing that dietary components modulate the microbiota, and, at the same time, the host metabolism is deeply influenced by the different products resulting from nutrient transformation in the microbiota compartment. This reciprocal relationship can potentially influence even drug metabolism for chronic drug regimens, significantly impacting human health/disease. Recently, the influence of various dietary restrictions on the gut microbiota and the differences between the effects were investigated. In this review, we explored the current knowledge of different dietary restrictions on animal and human gut microbiota and the impact of these changes on human health.

This study evaluated the effects of dietary supplementation with a postbiotic extract of Bifidobacterium breve BB091109 on pro-inflammatory cytokines levels and markers of endocrine function. A prospective, double-blind, placebo-controlled, randomized, single-centered, parallel study was conducted on a group of 40-55-year-old females. The study included 30 healthy females, divided into two groups: a supplement (n = 20) and a placebo (n = 10) groups. Blood and saliva samples were collected at baseline (wk0), after 4 weeks (wk 4) and 12 weeks (12wk) of daily supplementation (500 mg), and 4 weeks (wk 16) after termination of supplementation. The levels of fasting CRP, IL-6, IL-10, TNF-α, IFN-γ, DHEA, estradiol, estriol, progesterone, cortisol and human growth hormone were analysed. The results revealed a significant effect of the 90-day supplementation with B. breve postbiotic extract on changes in CRP, IL-6 levels, DHEA, estradiol and estriol. In conclusion, the supplementation with the B. breve postbiotic extract improved endocrine function in females over 40 years old and induced protective changes in inflammatory markers. These findings highlight the potential health benefits of this supplementation in promoting hormonal balance and reducing inflammation in this population.

Several observational studies have reported the correlation between gut microbiota and the risk of erectile dysfunction (ED). However, the causal association between them remained unestablished owing to intrinsic limitations, confounding factors, and reverse causality. Therefore, the two-sample Mendelian randomization (MR) study was performed to determine the causal effect of gut microbiota on the risk of ED.

The MR analysis utilized the publicly available genome-wide association study (GWAS) summary-level data to explore the causal associations between gut microbiota and ED. The gut microbiota data were extracted from the MiBioGen study (N = 18,340), and the ED data were extracted from the IEU Open GWAS (6,175 ED cases and 217,630 controls). The single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) by two thresholds of P-values, the first P-value setting as <1e-05 (locus-wide significance level) and the second P-value setting as <5e-08 (genome-wide significance level). The inverse variance weighted approach was used as the primary approach for MR analysis, supplemented with the other methods. In addition, sensitivity analyses were performed to evaluate the robustness of the MR results, including Cochran's Q test for heterogeneity, the MR-Egger intercept test for horizontal pleiotropy, the Mendelian randomization pleiotropy residual sum, and outlier (MR-PRESSO) global test for outliers, and the forest test and leave-one-out test for strong influence SNPs.

Our results presented that the increased abundance of Lachnospiraceae at family level (OR: 1.265, 95% CI: 1.054-1.519), Senegalimassilia (OR: 1.320, 95% CI: 1.064-1.638), Lachnospiraceae NC2004 group (OR: 1.197, 95% CI: 1.018-1.407), Tyzzerella3 (OR: 1.138, 95% CI: 1.017-1.273), and Oscillibacter (OR: 1.201, 95% CI: 1.035-1.393) at genus level may be risk factors for ED, while the increased abundance of Ruminococcaceae UCG013 (OR: 0.770, 95% CI: 0.615-0.965) at genus level may have a protective effect on ED. No heterogeneity or pleiotropy was found based on the previously described set of sensitivity analyses.

Our MR analysis demonstrated that the gut microbiota had inducing and protective effects on the risk of ED. The results provide clinicians with novel insights into the treatment and prevention of ED in the future. Furthermore, our study also displays novel insights into the pathogenesis of microbiota-mediated ED.

The gut microbiota has been gaining attention due to its interactions with the human body and its role in pathophysiological processes. One of the main interactions is the "gut-liver axis," in which disruption of the gut mucosal barrier seen in portal hypertension and liver disease can influence liver allograft function over time. For example, in patients who are undergoing liver transplantation, preexisting dysbiosis, perioperative antibiotic use, surgical stress, and immunosuppressive use have each been associated with alterations in gut microbiota, potentially impacting overall morbidity and mortality. In this review, studies exploring gut microbiota changes in patients undergoing liver transplantation are reviewed, including both human and experimental animal studies. Common themes include an increase in Enterobacteriaceae and Enterococcaceae species and a decrease in Faecalibacterium prausnitzii and Bacteriodes, while a decrease in the overall diversity of gut microbiota after liver transplantation.

As a long-term condition that affects the airways and lungs, chronic obstructive pulmonary disease (COPD) is characterized by inflammation, emphysema, breathlessness, chronic cough, and sputum production. Currently, the bronchodilators and anti-inflammatory drugs prescribed for COPD are mostly off-target, warranting new disease management strategies. Accumulating research has revealed the gut-lung axis to be a bidirectional communication system. Cigarette smoke, a major exacerbating factor in COPD and lung inflammation, affects gut microbiota composition and diversity, causing gut microbiota dysbiosis, a condition that has recently been described in COPD patients and animal models. For this review, we focused on the gut-lung axis, which is influenced by gut microbial metabolites, bacterial translocation, and immune cell modulation. Further, we have summarized the findings of preclinical and clinical studies on the association between gut microbiota and COPD to provide a basis for using gut microbiota in therapeutic strategies against COPD. Our review also proposes that further research on probiotics, prebiotics, short-chain fatty acids, and fecal microbiota transplantation could assist therapeutic approaches targeting the gut microbiota to alleviate COPD.

Sepsis stands as a dire medical condition, arising when the body's immune response to infection spirals into overdrive, paving the way for potential organ damage and potential mortality. With intestinal flora's known impact on sepsis but a dearth of comprehensive data, our study embarked on a two-sample Mendelian randomization analysis to probe the causal link between gut microbiota and their metabolites with severe sepsis patients who succumbed within a 28-day span.

Leveraging data from Genome-wide association study (GWAS) and combining it with data from 2,076 European descendants in the Framingham Heart Study, single-nucleotide polymorphisms (SNPs) were employed as Instrumental Variables (IVs) to discern gene loci affiliated with metabolites. GWAS summary statistics for sepsis were extracted from the UK Biobank consortium.

In this extensive exploration, 93 distinct genome-wide significant SNPs correlated with gut microbial metabolites and specific bacterial traits were identified for IVs construction. Notably, a substantial link between Coprococcus2 and both the incidence (OR of 0.80, 95% CI: 0.68-0.94, P=0.007) and the 28-day mortality rate (OR 0.48, 95% CI: 0.27-0.85, P=0.013) of sepsis was observed. The metabolite α-hydroxybutyrate displayed a marked association with sepsis onset (OR=1.08, 95% CI: 1.02-1.15, P=0.006) and its 28-day mortality rate (OR=1.17, 95% CI: 1.01-1.36, P=0.029).

This research unveils the intricate interplay between the gut microbial consortium, especially the genus Coprococcus, and the metabolite α-hydroxybutyrate in the milieu of sepsis. The findings illuminate the pivotal role of intestinal microbiota and their metabolites in sepsis' pathogenesis, offering fresh insights for future research and hinting at novel strategies for sepsis' diagnosis, therapeutic interventions, and prognostic assessments.

The circulation is a closed system that has been assumed to be free from bacteria, but evidence for the existence of a low-density blood microbiota is accumulating. The present study aimed to map the blood microbiota of outpatients with Crohn's disease (CD) or with ulcerative colitis (UC) by 16S metagenomics. A diverse microbiota was observed in the blood samples. Regardless of the type of disease, the alpha diversity of the microbiota was positively associated with C-reactive protein (CRP). The blood microbiota had a surprisingly high proportion of Proteobacteria in comparison with human oral and colonic microbiotas. There was no clear difference in the overall pattern of the microbiota between CD and UC. A non-template control (NTC) was included in the whole process to control for the potential contamination from the environment and reagents. Certain bacterial taxa were concomitantly detected in both blood samples and NTC. However, Acinetobacter, Lactobacillus, Thermicanus and Paracoccus were found in blood from both CD and UC patients but not in NTC, indicating the existence of a specific blood-borne microbiota in the patients. Achromobacter dominated in all blood samples, but a minor amount was also found in NTC. Micrococcaceae was significantly enriched in CD, but it was also detected in high abundance in NTC. Whether the composition of the blood microbiota could be a marker of a particular phenotype in inflammatory bowel disease (IBD) or whether the blood microbiota could be used for diagnostic or therapeutic purposes deserves further attention.

The real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D.

We leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy.

At the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P _FDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P _FDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10^-4, P _FDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected.

The present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa's role in the pathophysiology of T1D.

Recent studies had provided evidence that the gut microbiota is associated with sepsis. However, the potential causal relationship remained unclear.

The present study aimed to explore the causal effects between gut microbiota and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association study (GWAS) summary-level data. Gut microbiota GWAS (N = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for sepsis were gained from the UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies were used to select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5) and the genome-wide statistical significance threshold (5 × 10-8) were chosen as instrumental variables (IVs). The inverse variance weighted (IVW) was used as the primary method for MR study, supplemented by a series of other methods. Additionally, a set of sensitivity analysis methods, including the MR-Egger intercept test, Mendelian randomized polymorphism residual and outlier (MR-PRESSO) test, Cochran's Q test, and leave-one-out test, were carried out to assess the robustness of our findings.

Our study suggested that increased abundance of Deltaproteobacteria, Desulfovibrionales, Catenibacterium, and Hungatella were negatively associated with sepsis risk, while Clostridiaceae1, Alloprevotella, LachnospiraceaeND3007group, and Terrisporobacter were positively correlated with the risk of sepsis. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy.

This study firstly found suggestive evidence of beneficial or detrimental causal associations of gut microbiota on sepsis risk by applying MR approach, which may provide valuable insights into the pathogenesis of microbiota-mediated sepsis and strategies for sepsis prevention and treatment.

Phage therapy, the use of bacteriophage viruses for bacterial infection treatment, has been around for almost a century, but with the increase in antibiotic use, its importance has declined rapidly. There has been renewed interest in revisiting this practice due to the general decline in the effectiveness of antibiotics, combined with improved understanding of human microbiota and advances in sequencing technologies. Phage therapy has been proposed as a clinical alternative to restore the gut microbiota in the absence of an effective treatment. That is due to its immunomodulatory and bactericidal effects against its target bacteria. In the gastrointestinal diseases field, phage therapy has been studied mainly as a promising tool in infectious diseases treatment, such as cholera and diarrhea. However, many studies have been conducted in non-communicable diseases, such as the targeting of adherent invasive Escherichia coli in Crohn's disease, the treatment of Clostridioides difficile in ulcerative colitis, the eradication of Fusobacterium nucleatum in colorectal cancer, the targeting of alcohol-producing Klebsiella pneumoniae in non-alcoholic fatty liver disease, or Enterococcus faecalis in alcohol-associated hepatitis. This review will summarize the changes in the gut microbiota and the phageome in association with some gastrointestinal and liver diseases and highlight the recent scientific advances in phage therapy as a therapeutic tool for their treatment.

Acute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.

The complex microbial community found in the human gut consist of members of multiple kingdoms, among which are bacteria and fungi. Microbiome research mainly focuses on the bacterial part of the microbiota, thereby neglecting interactions that can take place between bacteria and fungi. With the rise of sequencing techniques, the possibilities to study cross-kingdom relationships has expanded. In this study, fungal-bacterial relationships were investigated using the complex, dynamic computer-controlled in vitro model of the colon (TIM-2). Interactions were investigated by disruption of either the bacterial or fungal community by the addition of antibiotics or antifungals to TIM-2, respectively, compared to a control without antimicrobials. The microbial community was analyzed with the use of next generation sequencing of the ITS2 region and the 16S rRNA. Moreover, the production of SCFAs was followed during the interventions. Correlations between fungi and bacteria were calculated to investigate possible cross-kingdom interactions. The experiments showed that no significant differences in alpha-diversity were observed between the treatments with antibiotics and fungicide. For beta-diversity, it could be observed that samples treated with antibiotics clustered together, whereas the samples from the other treatments were more different. Taxonomic classification was done for both bacteria and fungi, but no big shifts were observed after treatments. At the level of individual genera, bacterial genus Akkermansia was shown to be increased after fungicide treatment. SCFAs levels were lowered in samples treated with antifungals. Spearman correlations suggested that cross-kingdom interactions are present in the human gut, and that fungi and bacteria can influence each other. Further research is required to gain more insights in these interactions and their molecular nature and to determine the clinical relevance.

In clinical practice, antidepressant drugs are widely used to treat depression. Previous studies have attention to the impact of antidepressants on the bacterial microbiome, while the role of these drugs in the gut virome is still unclear.

In this study, we estimated the effects of antidepressant amitriptyline (Ami), fluoxetine (Flu), and traditional Chinese medicine Xiaoyaosan (XYS) administration on gut viral composition and function in a chronic unpredictable mild stress (CUMS)-induced depression rat model based on shotgun metagenomic sequencing.

The results showed that treatment with Ami, Flu, and XYS significantly changed the gut viral composition compared with the CUMS-induced rats. At the family level, the abundance of f_unclassified_Caudovirales in CUMS rats was remarkably lower than in the HC rats, nevertheless, XYS significantly recovered the abundance of Caudovirales. Meanwhile, the abundance of Podoviridae was expanded in CUMS rats compared with the HC rats, and the profile was then significantly reduced after XYS treatment. Furthermore, both antidepressants and XYS increased the abundance of Siphoviridae compared with the CUMS rats, but only Ami treatments had significant differences. Subsequent function annotation further implied that Ami, Flu, and XYS showed to involve an alteration of the diverse viral functions, such as carbohydrate metabolism, xenobiotics biodegradation and metabolism, community-prokaryotes, translation, and neurodegenerative disease. Additionally, the co-occurrence network displayed that there are complex interactions between viral operational taxonomic units (vOTUs) represented by temperate phages and the majority of bacterial genera in the intestine ecosystem.

Our study proved for the first time that depression is characterized by massive alterations and functional distortion of the gut viruses, and after oral administration of Ami, Flu, and XYS could affect disordered gut virome, which could be a novel target in depression.

Irritable Bowel Syndrome (IBS) is the most common gastrointestinal (GI) disorder in Western populations and therefore a major public health/economic concern. However, despite extensive research, psychological and physiological factors that contribute to the aetiology of IBS remain poorly understood. Consequently, clinical management of IBS is reduced to symptom management through various suboptimal options. Recent evidence has suggested human milk oligosaccharides (HMOs) as a potential therapeutic option for IBS. Here, we review literature concerning the role of HMOs in IBS, including data from intervention and in vitro trials. HMO supplementation shows promising results in altering the gut microbiota and improving IBS symptoms, for instance by stimulating bifidobacteria. Further research in adults is required into HMO mechanisms, to confirm the preliminary results available to date and recommendations of HMO use in IBS.

Despite advances in treatment strategies, breast cancer (BC) remains one of the most prevalent cancers worldwide. Recent studies implicate the gut microbiome as a potential risk factor for BC development. Alterations in gut microbial diversity resulting in dysbiosis have been linked to breast carcinogenesis by modulating host immune responses and inflammatory pathways, favoring tumorigenesis and progression. Moreover, gut microbiota populations are different between women with BC vs those that are cancer free, further implicating the role of the gut microbiome in cancer development. This alteration in gut microbiota is also associated with changes in estrogen metabolism, which strongly correlates with BC development. Gut microbiota that express the enzyme β-glucuronidase (GUS) may increase estrogen bioavailability by deconjugating estrogen-glucuronide moieties enabling reabsorption into circulation. Increased circulating estrogens may, in turn, drive estrogen receptor-positive BC. GUS-expressing microbiota also affect cancer therapy efficacy and toxicity by modifying glucuronide-conjugated drug metabolites. Therefore, GUS inhibitors have emerged as a potential antitumor treatment. However, the effectiveness of GUS inhibitors is still exploratory. Further studies are needed to determine how oral endocrine-targeting therapies may influence or be influenced by the microbiota and how that may affect carcinogenesis initiation and tumor recurrence.

Functional dyspepsia (FD) is a common and debilitating gastrointestinal disorder attributed to altered gut-brain interactions. While the etiology of FD remains unknown, emerging research suggests the mechanisms are likely multifactorial and heterogenous among patient subgroups. Small bowel motor disturbances, visceral hypersensitivity, chronic microinflammation, and increased intestinal tract permeability have all been linked to the pathogenesis of FD. Recently, alterations to the gut microbiome have also been implicated to play an important role in the disease. Changes to the duodenal microbiota may either trigger or be a consequence of immune and neuronal disturbances observed in the disease, but the mechanisms of influence of small intestinal flora on gastrointestinal function and symptomatology are unknown.

This review summarizes and synthesizes the literature on the link between the microbiota, low-grade inflammatory changes in the duodenum and FD. This review is not intended to provide a complete overview of FD or the small intestinal microbiota, but instead outline some of the key conceptual advances in understanding the interactions between altered gastrointestinal bacterial communities; dietary factors; host immune activation; and stimulation of the gut-brain axes in patients with FD versus controls. Current and emerging treatment approaches such as dietary interventions and antibiotic or probiotic use that have demonstrated symptom benefits for patients are reviewed, and their role in modulating the host-microbiota is discussed. Finally, suggested opportunities for diagnostic and therapeutic improvements for patients with this condition are presented.