Gut Flora Research Articles

Exosomes in Autoimmune Diseases: A Review of Mechanisms and Diagnostic Applications.

Exosomes, small extracellular vesicles secreted by various cell types, have emerged as key players in the pathophysiology of autoimmune diseases. These vesicles serve as mediators of intercellular communication, facilitating the transfer of bioactive molecules such as proteins, lipids, and nucleotide. In autoimmune diseases, exosomes have been implicated in modulating immune responses, oxidative stress, autophagy, gut microbes, and the cell cycle, contributing to disease initiation, progression, and immune dysregulation. Recent advancements in exosome isolation techniques and their molecular characterization have paved the way for exploring their clinical potential as biomarkers and therapeutic targets. This review focuses on the mechanisms by which exosomes influence autoimmune disease development and their potential clinical applications, particularly in diagnosis. The role of exosomes in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), inflammatory bowel disease (IBD), and Sjögren's syndrome (SS), is discussed in relation to their involvements in antigen presentation, T-cell activation, and the induction of inflammatory pathways. Additionally, exosome-based biomarkers offer promising non-invasive diagnostic tools for early diagnostic, disease monitoring, and therapeutic response assessment. However, challenges such as standardization of exosome isolation protocols and validation of their clinical significance remain. This review highlights the potential of exosomes as both diagnostic biomarkers and therapeutic targets in autoimmune diseases, emphasizing the need for further research to overcome current limitations and fully harness their clinical value.

Lactobacillus gasseri prevents ibrutinib-associated atrial fibrillation through butyrate.

Ibrutinib, a widely used anti-cancer drug, is known to significantly increase the susceptibility to atrial fibrillation (AF). While it is recognized that drugs can reshape the gut microbiota, influencing both therapeutic effectiveness and adverse events, the role of gut microbiota in ibrutinib-induced AF remains largely unexplored. Utilizing 16S rRNA gene sequencing, fecal microbiota transplantation, metabonomics, electrophysiological examination, and molecular biology methodologies, we sought to validate the hypothesis that gut microbiota dysbiosis promotes ibrutinib-associated AF and to elucidate the underlying mechanisms. We found that ibrutinib administration predisposes rats to AF. Interestingly, ibrutinib-associated microbial transplantation conferred increased susceptibility to AF in rats. Notably, ibrutinib induced a significantly decrease in the abundance of Lactobacillus gasseri (L. gasseri), and oral supplementation of L. gasseri or its metabolite, butyrate, effectively prevented rats from ibrutinib-induced AF. Mechanistically, butyrate inhibits the generation of reactive oxygen species (ROS), thereby ameliorating atrial structural remodeling. Furthermore, we demonstrated that ibrutinib inhibited the growth of L. gasseri by disrupting the intestinal barrier integrity. Collectively, our findings provide compelling experimental evidence supporting the potential efficacy of targeting gut microbes in preventing ibrutinib-associated AF, opening new avenues for therapeutic interventions.

Spatial variations in the microbiota: comparative analysis of microbial composition and predicted functions across different intestinal segments and feces in donkeys

Donkeys, as single-stomach herbivores, have a complex and diverse microbial community in their digestive tracts. The intestinal bacterial community is crucial for maintaining intestinal homeostasis, as well as the host’s overall nutrition and health. However, research on donkey gut microbes is relatively limited, particularly regarding the microbial colonization patterns in different intestinal segments of adult donkeys. Therefore, this study examined the abundance and function of microbiota across various sites of the intestinal tract (duodenum, jejunum, ileum, cecum, colon) and feces of healthy adult Dezhou male donkeys using 16S rRNA gene sequencing and PICRUSt analysis. The results indicate that donkeys have a rich gut microbial diversity and a large microbial population. No significant differences in the indices of alpha diversity were observed among the donkey’s duodenum, jejunum, ileum, cecum, colon, and feces. A Venn diagram analysis revealed the presence of both unique (Duodenum: 4645; Jejunum: 3586; Ileum: 4904; Cecum: 4253; Colon: 6135; Feces: 4885) and shared (339) ASVs among the different sections. A principal coordinate analysis (PCoA) revealed significant differences (R2 = 0.2076, p < 0.007) across the six intestinal segments of the donkeys. At the phylum level, Firmicutes (63.64%), Bacteroidetes (20.72%), Verrucomicrobiota (9.16%), Patescibacteria (1.95%), Spirochaetota (1.87%), Actinobacteriota (1.13%), and Proteobacteria (0.42%) were the dominant bacteria in all samples. The Wilcoxon rank-sum test revealed significant differences in the proportions of genera among different intestinal segments. Specific genera were significantly enriched in various segments: Lachnospiraceae_UCG-008 and Sphaerochaeta in the duodenum; Christensenellaceae_R-7_group and Bacillus in the jejunum; NK4A214_group and Alloprevotella in the ileum; UCG-005 and Lactobacillus in the cecum; Clostridium_sensu_stricto_1 and Chlamydia in the colon; and Rikenellaceae_RC9_gut_group and Prevotellaceae_UCG-004 in the feces. A PICRUSt2 functional prediction analysis indicated that carbohydrate metabolism, prokaryotic cellular communities, antimicrobial drug resistance, immune diseases, membrane transport, signal transduction, and transcription exhibited significant differences among the different intestinal segments. This study provided critical primary data on the differences in donkey gut microbiota and the synergistic effects between gut microbiota and host functions. These findings can be used to assess donkey health status, improve breeding, and develop microbial additives.

Microbially produced imidazole propionate impairs prostate cancer progression through PDZK1

BackgroundA close relationship exists between castration-resistant prostate cancer (CRPC) and histidine metabolism by gut microbes. However, the effects of the histidine metabolite imidazole propionate (IMP) on prostate cancer (PCa) and its underlying mechanisms are not well understood.MethodsWe first assessed the effects of IMP on cell proliferation and migration at the cellular level. Subsequently, we investigated the mechanism of action of IMP using transcriptome sequencing, qPCR, and Western blot analysis. Finally, we validated our findings in vivo using a mouse model.ResultsHistidine had no effect on PCa cell proliferation; however, IMP significantly inhibited the proliferation and migration of PC3 and DU145 cells. Mechanistic studies indicate that IMP exerts its effects by upregulating PDZK1 expression, which subsequently inhibits the phosphorylation of the PI3K-AKT pathway.ConclusionsIn conclusion, IMP significantly inhibits the progression of PCa, offering new insights into potential treatments for CRPC.

Core microbe Bifidobacterium in the hindgut of calves improves the growth phenotype of young hosts by regulating microbial functions and host metabolism

BackgroundThe growth and health of young ruminants are regulated by their gut microbiome, which can have lifelong consequences. Compared with subjective grouping, phenotypic clustering might be a more comprehensive approach to revealing the relationship between calf growth state and core gut microbes. However, the identification of beneficial gut bacteria and its internal mechanisms of shaping host phenotype differentiation remains unclear.ResultsIn this study, calves were divided into two clusters, cluster1 and cluster2, based on 29 phenotypic indicators using cluster analysis. Calves in cluster2 showed better growth performance, including higher body weight (BW), average daily gain (ADG), and dry matter intake (DMI), as well as better serum indicators with a high level of total superoxide dismutase (T-SOD), interleukin-6 (IL-6), and insulin-like growth factor-1 (IGF-1) compared to those in cluster1. Multi-omics was used to detect microbial features among calves in different phenotypic clusters. Distinct differences were observed between the two clustered gut microbiomes, including microbial diversity and composition. The close relationships between growth performance, blood metabolites, and microbiome were also confirmed. In cluster2, Bifidobacterium members were the dominant contributors to microbial metabolic functions with a higher abundance. Furthermore, pathways involved in carbohydrate degradation, glycolysis, and biosynthesis of propionate and proteins were active, while methane production was inhibited. In addition, the diversity and richness of hindgut resistome in cluster2 were lower than those in cluster1. The isolation and culture of Bifidobacterium strain, as well as the mice experiment, indicated that B. longum 1109 from calf feces in cluster2 could promote the growth of young hosts, enhance their blood immunity and antioxidation, and improve the development of hindgut.ConclusionsIn summary, cluster analysis has proved to be a feasible and reliable approach for identifying phenotypic subgroups of calves, prompting further exploration of host-microbiome interactions. Bifidobacterium as a core microbe in the hindgut of calves may play a crucial probiotic role in host phenotypic differentiation. This study enhances our comprehension of how gut core microbe shapes the host phenotype and provides new insights into the manipulation of beneficial gut colonizers to improve the growth performance and productivity of young ruminants.EbRLLe7F-yvVZ5Dd-FAxmeVideo

Metagenome-guided culturomics for the targeted enrichment of gut microbes

The gut microbiome significantly impacts human health, yet cultivation challenges hinder its exploration. Here, we combine deep whole-metagenome sequencing with culturomics to selectively enrich for taxa and functional capabilities of interest. Using a modified commercial base medium, 50 growth modifications were evaluated, spanning antibiotics, physico-chemical conditions, and bioactive compounds. Whole-metagenome sequencing identified medium additives, like caffeine, that enhance taxa often associated with healthier subjects (e.g., Lachnospiraceae, Oscillospiraceae, Ruminococcaceae). We also explore the impact of modifications on the composition of cultured communities and establish a link between medium preference and microbial phylogeny. Leveraging these insights, we demonstrate that combinations of media modifications can further enhance the targeted enrichment of taxa and metabolic functions, such as Collinsella aerofaciens, or strains harboring biochemical pathways involved in dopamine metabolism. This streamlined, scalable approach unlocks the potential for selective enrichment, advancing microbiome research by understanding the impact of different cultivation parameters on gut microbes.

Gut colonization of Bacteroides plebeius suppresses colitis-associated colon cancer development.

Colon cancer development may be initiated by multiple factors, including chronic inflammation, genetic disposition, and gut dysbiosis. The loss of beneficial bacteria and increased abundance of detrimental microbes exacerbates disease progression. Bacteroides plebeius (B. plebeius) is a human gut microbe, and its colon colonization is enhanced by a seaweed-supplemented diet. We found that mice orally administered with B. plebeius and fed a diet containing 1% seaweed developed a unique gut microbial composition. By linear discriminant analysis effect size analysis, we found that B. plebeius colonization increased the abundance of Blautia coccoides and reduced the abundance of Akkermansia sp. and Dubosiella sp. We also showed that colonization of B. plebeius suppressed the colon tumor development induced by azoxymethane/dextran sulfate sodium in specific-pathogen-free mice, coinciding with a reduced abundance of Muribaculaceae sp., Closteridale sp., and Bilophila sp. Moreover, B. plebeius colonization in gnotobiotic mice resulted in enhanced production of selected metabolites, including propionic, taurocholic, cholic, alpha-, and beta-muricholic, as well as ursodeoxycholic acids. Importantly, some of these metabolites show anti-inflammatory and tumor-suppressive effects. We conclude that B. plebeius is able to restructure the gut microbial community and produce beneficial metabolites, leading to inhibition of colitis-associated colon cancer development.IMPORTANCEThis work delves into the pivotal role of gut microbiota in suppressing the progression of colitis-associated colon cancer. By investigating the impact of Bacteroides plebeius that can be colonized in mouse gut by feeding the animal with seaweed diet, we unveil a novel mechanism through which this beneficial bacterium reshapes the gut microbial community and produces metabolites with anti-inflammatory and tumor-suppressive properties. Such findings underscore the potential of harnessing specific microbes, like B. plebeius shown in this study, to modulate the gut ecosystem and mitigate the risk of colitis-associated colon cancer.

Relationship Between Depression and Epigallocatechin Gallate from the Perspective of Gut Microbiota: A Systematic Review

Depression, a serious mental illness, is characterized by high risk, high incidence, persistence, and tendency to relapse, posing a significant burden on global health. The connection between depression and gut microbiota is an emerging field of study in psychiatry and neuroscience. Understanding the gut–brain axis is pivotal for understanding the pathogenesis and treatment of depression. Gut microbes influence depression-like behaviors by impacting the hypothalamic–pituitary–adrenal axis (HPA), monoamine neurotransmitters, immune responses, cell signaling, and metabolic pathways. Tea, widely used in clinical practice to improve neuropsychiatric disorders, contains Epigallocatechin gallate (EGCG), a major ingredient of green tea, which effectively regulates intestinal flora. This review examined the risks and causes of depression, the complications associated with intestinal flora, their role in the development and treatment of depression, and how EGCG may alleviate depression through interactions with gut microbiota and other mechanisms.

Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface.

The gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health. Variation in bacterial load and composition along the GI tract may influence the mucosal microenvironment and thus be reflected its interstitial fluid (IF). Characterization of the segment-specific microenvironment is challenging and largely unexplored because of lack of available tools. Here, we developed methods, namely tissue centrifugation and elution, to collect IF from the mucosa of different intestinal segments. These methods were first validated in rats and mice, and the tissue elution method was subsequently translated for use in humans. These new methods allowed us to quantify microbiota-derived metabolites, mucosa-derived cytokines, and proteins at their site-of-action. Quantification of short-chain fatty acids showed enrichment in the colonic IF. Metabolite and cytokine analyses revealed differential abundances within segments, often significantly increased compared to plasma, and proteomics revealed that proteins annotated to the extracellular phase were site-specifically identifiable in IF. Lipopolysaccharide injections in rats showed significantly higher ileal IL-1β levels in IF compared to the systemic circulation, suggesting the potential of local as well as systemic effect. Collection of IF from defined segments and the direct measurement of mediators at the site-of-action in rodents and humans bypasses the limitations of indirect analysis of faecal samples or serum, providing direct insight into this understudied compartment.

Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis

Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid. Levels of these metabolites were negatively associated with atherosclerosis burden. Furthermore, we show that 3,4-DHBA prevented lipopolysaccharide (LPS)-induced decrease in transendothelial electrical resistance (TEER). These results suggest that the effects of quercetin on atherosclerosis are influenced by gut microbes and are potentially mediated by bacterial metabolites derived from the flavonoid.

Non‐differential gut microbes contribute to hypertension and its severity through co‐abundances: A multi‐regional prospective cohort study

AbstractMicrobial dysbiosis, characterized by an imbalanced microbial community structure and function, has been linked to hypertension. While prior research has primarily focused on differential abundances, our study highlights the role of non‐differential microbes in hypertension. We propose that non‐differential microbes contribute to hypertension through their ecological interactions, as defined by co‐abundances (pairs of microbes exhibiting correlated abundance patterns). Using gut microbiome data from the Guangdong Gut Microbiome Project, which includes 2355 hypertensive and 4644 non‐hypertensive participants across 14 regions, we identified replicable hypertension‐related microbial interactions. Notably, most co‐abundances involved non‐differential microbes, which were found to correlate with both hypertension severity and hypertension‐related microbial metabolic pathways. These findings emphasize the importance of microbial interactions in hypertension pathogenesis and propose a novel perspective for microbiome‐based therapeutic strategies.

Investigating Causal Associations of Gut Microbiota and Blood Metabolites on Stroke and its Subtypes: A Mendelian Randomization Study.

The causal relationships between gut microbiota, blood metabolites, and stroke and its subtypes remain unclear. This study aims to uncover the causal associations using Mendelian randomization. We initially identify Single-Nucleotide Polymorphisms (SNPs) correlated with gut microbiota and blood metabolites as instrumental variables (IVs) from the summary statistics in Genome-Wide Association Study (GWAS) to evaluate their potential causal associations with stroke and its subtypes. We proceed with a two-step Mendelian randomization analysis aiming to determine whether blood metabolites mediate the relationships between gut microbiota and stroke or its subtypes. We identified the genetic predictions of 12, 11, and 10 particular gut microbiota were associated with stroke, ischemic stroke, and intracerebral hemorrhage respectively. Inverse variance weighted (IVW) analysis disclosed Alistipes (OR [95%CI]: 1.11[1.00,1.23]), Streptococcus (OR [95%CI]: 1.17[1.05,1.30]), and Porphyromonadaceae (OR [95%CI]: 2.41[1.09,5.31]) as the primary causal effects on stroke, ischemic stroke, and ICH, respectively. We determined that 8, 11, and 1 blood metabolites were causally related to stroke, ischemic stroke, and ICH, respectively. Among these metabolites, Citrate (OR [95%CI]: 2.39[1.32,4.34]) and Beta-hydroxyisovalerate (OR [95%CI]: 2.54[1.62,3.97]) had the foremost causal effect on stroke and ischemic stroke, respectively, whereas Glutaroyl carnitine evidenced a causal effect on ICH. Furthermore, our study revealed that Tetradecanedioate marginally mediated the causal effects of Paraprevotella on stroke and ischemic stroke. This study established a causal link between gut microbiota, plasma metabolites, and stroke. It revealed a marginal pathway, shedding new light on the intricate interactions among gut microbes, blood metabolites, stroke, and their underlying mechanisms.

Sequential Versus Continuous Feeding and Its Effect on the Gut Microbiota in Critically Ill Patients: A Randomized Controlled Trial.

Gut microbiota disturbance may worsen critical illnesses and is responsible for the progression of multiple organ dysfunction syndrome. In our previous study, there was a trend towards a higher α-diversity of the gut microbiota in sequential feeding (SF) than in continuous feeding (CF) for critically ill patients. We designed this non-blinded, randomized controlled study to confirm these results. All the enrolled patients received continuous feeding in the beginning. After achieving ≥80% of the nutrition target calories (25-30 kcal/kg/d), the patients were randomized into the SF group or the CF group. In the SF group, continuous feeding was changed into intermittent feeding. The total daily dosage of enteral nutrition was equally distributed during three periods at 7-9:00, 11-13:00 and 17-19:00. After 7 days of randomization, fresh stool and serum were collected for 16S rRNA gene sequencing and untargeted metabolomics analysis respectively. Meanwhile, routine blood test indicators and metabolic indicators were recorded. Finally, data from 65 patients in the SF group and 69 patients in the CF group were used for intention-to-treat analysis. There was no difference in the Shannon index between the SF group and CF group [2.5 (1.7-3.4) vs. 2.6 (1.5-3.5), P =0.934]. However, at the genus level, the abundances of Erysipelotrichaceae_UCG-003 and Howardella increased in the SF group. Some metabolic indicators (the albumin level, total cholesterol level and total bile acid level) and the increases in lymphocyte counts in the SF group were different from those in the CF group (P <0.05). In untargeted metabolomic analysis, 58 differentially abundant metabolites between the two groups were found. The pathway with the highest enrichment factors was primary bile acid biosynthesis according to the Kyoto Encyclopedia of Genes and Genomes Database classification. Regarding adverse events, the gut tolerance, average glucose and incidence of hyperglycemia and hypoglycemia were similar between the SF group and CF group. The mortality rate in the SF group was lower than that in the CF group, but there was no statistical difference (9.2% vs. 13.0%, P=0.484). SF did not increase the diversity of gut microbiota in critically ill patients. However, it did alter the abundances of some gut microbes and affect some metabolites. Its clinical significance requires further exploration. In addition, the gut tolerance and safety of SF were similar to that of CF. www. gov, registration number NCT04443335. Registered 21 June, 2020.

Developmental & Comparative Immunology Lipoxin B4 and lipocalin play a crucial role in insect immune-priming induced by a gut microbial commensal.

Host cabbage possesses an endophyte, Bacillus subtilis, which induced immune-priming of the diamondback moth, Plutella xylostella. In contrast, larvae raised under axenic conditions lost the chance to feed the bacteria and were highly susceptible to various pathogens. Addition of B. subtilis to axenic larvae significantly restored immune responses and enhanced survival rates following pathogen infections. The immune-priming factor(s) was determined among 18 apolipoprotein D (ApoD) genes identified as lipocalin candidates in P. xylostella, in which ApoD1 expression was functionally linked with B. subtilis-induced immune-priming. In addition, lipoxins were analyzed in immune-primed larvae via LC-MS/MS, in which LXB4 was detected, but not LXA4. The LXB4 titer was significantly higher than that that in the larvae reared under axenic conditions. Notably, LXB4 alone sufficiently induced significant immune responses. To support lipoxin biosynthesis in insects, this study identified a lipoxygenase-like peroxidase gene, HemP2. Its expression was induced in the immune-primed larvae. However, its suppression prevented LXB4 production under the immune-priming conditions. To explain the up-regulations of lipocalin/lipoxin by the gut commensal, Toll and IMD immune signaling pathways were analyzed. The up-regulation of ApoD1 and HemP2 expressions was mediated through the IMD, but not the Toll, immune signaling pathway in the larval gut of P. xylostella under B. subtilis-induced immune-priming conditions. This study highlights the potential role of commensal gut microbes including B. subtilis in driving immune-priming via an insect lipoxin-lipocalin complex through the IMD immune signaling pathway.

Gut microbes of the cecum versus the colon drive more severe lethality and multi-organ damage.

Intestinal perforations lead to a high risk of sepsis-associated morbidity and multi-organ dysfunctions. A perforation allows intestinal contents (IC) to enter the peritoneal cavity, causing abdominal infections. Right- and left-sided perforations have different prognoses in humans, but the mechanisms associated with different cecum and colon perforations remain unclear. This study investigates how gut flora influences outcomes from perforations at different sites in mice. Using fecal-induced peritonitis mouse model, isolated IC from the cecum or colon was injected peritoneally at 2mg/kg. Bacterial burden was quantified with quantitative PCR, and microbial communities were analyzed using 16S rRNA gene sequencing. Survival rates were monitored, and blood biochemical indices, histological changes, cytokines expression, immunological signaling and multiple-organ damage were assessed at 16h post-injections. The results showed cecum IC developed more severe sepsis than colon IC, with shorter median survival time and greater multi-organ damage. Mice treated with cecum IC displayed elevated tissue damage markers in the liver, heart, and kidneys, contributing to worsened pathology. This was likely driven by systematic inflammatory cytokines production and lung inflammation. Mechanistically, cecum IC triggered stronger cGAS-STING and TBK1-NF-κB signaling, promoting systemic inflammation compared to the colon IC. Moreover, bacterial analysis demonstrated that cecum IC carry a higher bacterial burden than colon IC and exhibit a different microbial community. A detailed microbiome comparison revealed an increased abundance of potentially pathogenic bacteria in the cecum IC. These findings suggest that the site of intestinal perforation influences sepsis severity, with the cecum being associated with a higher bacterial burden and a relatively increased abundance of potentially pathogenic bacteria compared to the colon. Our findings first compared the lethality associated with the microbial composition of the cecum and colon, indicating the perforation site could help providers predict the severity of sepsis, thereby introducing a novel perspective to microbiology and sepsis research.

Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives.

Flavonoids are naturally occurring dietary phytochemicals with significant antioxidant effects aside from several health benefits. People often consume them in combination with other food components. Compiling data establishes a link between bioactive flavonoids and prevention of several diseases in animal models, including cardiovascular diseases, diabetes, gut dysbiosis, and metabolic dysfunction-associated steatotic liver disease (MASLD). However, numerous clinical studies have demonstrated the ineffectiveness of flavonoids contradicting rodent models, thereby challenging the validity of using flavonoids as dietary supplements. This review provides a clinical perspective to emphasize the effective roles of dietary flavonoids as well as to summarize their specific mechanisms in animals briefly. First, this review offers an in-depth elucidation of the metabolic processes of flavonoids within human, encompassing the small, large intestine, and the liver. Furthermore, the review provides a comprehensive overview of the various functions of flavonoids in the gastrointestinal tract, including hindering the breakdown and assimilation of macronutrients, such as polysaccharides and lipids, regulating gut hormone secretion as well as inhibition of mineral iron absorption. In the large intestine, an unabsorbed major portion of flavonoids interact with the gut flora leading to their biotransformation. Once absorbed and circulated in the bloodstream, bioactive flavonoids or their metabolites exert numerous beneficial systemic effects. Lastly, we examine the protective effects of flavonoids in several metabolic disorders, including endothelial dysfunction, MASLD, cardiovascular disease, obesity, hyperlipidemia, and insulin resistance. In conclusion, this review outlines the safety and future prospects of flavonoids in the field of health, especially in the prevention of metabolic syndrome (MetS).

Oral amoxicillin treatment disrupts the gut microbiome and metabolome without interfering with luminal redox potential in the intestine of Wistar Han rats.

Oral antibiotic treatment is well known to be one of the main factors affecting gut microbiota composition by altering bacterial diversity. It decreases the abundance of butyrate-producing bacteria such as Lachnospiraceae and Ruminococcaceae, while increasing abundance of Enterobacteriaceae. The recovery time of commensal bacteria post-antibiotic treatment varies among individuals, and often, complete recovery is not achieved. Recently, gut microbiota disruption has been associated with increased gut oxygen levels and higher redox potential in faecal samples. Given that redox balance is crucial for microbial metabolism and gut health, influencing fermentation processes and maintaining anaerobic conditions, we investigated the impact of oral amoxicillin treatment on the redox potential in the caecum. We used 24 Wistar Han male rats and measured caecal redox potential in situ with a probe, before and after 7 days of amoxicillin treatment, as well as after 7 days of recovery. Additionally, we analysed caecal weight, pH, antioxidant capacity, caecal microbiota, metabolome, and colonic tissue expression of relevant genes involved in the redox potential state. Our findings show that oral amoxicillin treatment significantly reduced archaeal load, and decreased the bacterial alpha diversity and affected bacterial composition of the caecal microbiome. The caecal metabolome was also significantly affected, exemplified by reduced amounts of short chain fatty acids during amoxicillin treatment. While the caecal metabolome fully recovered seven days post amoxicillin treatment, the microbiome did not fully recover within this time frame. However, amoxicillin did not lead to an increase in luminal redox potential in the cecum during or post amoxicillin treatment. Limited differences were observed for colonic expression of genes involved in intestinal barrier function and generation of reactive oxygen species, except for the catalase gene, which was significantly upregulated post-amoxicillin treatment. Our results suggest that while oral amoxicillin disrupts the gut microbiome and metabolome, it does not directly interfere with gut luminal redox state.

Harnessing gut microbial communities to unravel microbiome functions.

The gut microbiome impacts human health in direct and indirect ways. While many associations have been discovered between specific microbiome compositions and diseases, establishing causality, understanding the underlying mechanisms, and developing successful microbiome-based therapies require novel experimental approaches. In this opinion, we discuss how in vitro cultivation of diverse communities enables systematic investigation of the individual and collective functions of gut microbes. Up to now, the field has relied mostly on simple, bottom-up assembled synthetic communities or more complex, undefined stool-derived communities. Although powerful for dissecting interactions and mapping causal effects, these communities suffer either from ignoring the complexity, diversity, coevolution, and dynamics of natural communities or from lack of control of community composition. These limitations can be overcome in the future by establishing personalized culture collections from stool samples of different donors and assembling personalized communities to investigate native interactions and ecological relationships in a controlled manner.

Seasonal Variations in the Structure and Function of the Gut Flora in Adult Male Rhesus Macaques Reared in Outdoor Colonies

Seasonal Variations in the Structure and Function of the Gut Flora in Adult Male Rhesus Macaques Reared in Outdoor Colonies

Deep learning-based differential gut flora for prediction of Parkinson's.

There had been extensive research on the role of the gut microbiota in human health and disease. Increasing evidence suggested that the gut-brain axis played a crucial role in Parkinson's disease, with changes in the gut microbiota speculated to be involved in the pathogenesis of Parkinson's disease or interfere with its treatment. However, studies utilizing deep learning methods to predict Parkinson's disease through the gut microbiota were still limited. Therefore, the goal of this study was to develop an efficient and accurate prediction method based on deep learning by thoroughly analyzing gut microbiota data to achieve the diagnosis of Parkinson's disease. This study proposed a method for predicting Parkinson's disease using differential gut microbiota, named the Parkinson Gut Prediction Method (PGPM). Initially, differential gut microbiota data were extracted from 39 Parkinson's disease (PD) patients and their corresponding 39 healthy spouses. Subsequently, a preprocessing method called CRFS (combined ranking using random forest scores and principal component analysis contributions) was introduced for feature selection. Following this, the proposed LSIM (LSTM-penultimate to SVM Input Method) approach was utilized for classifying Parkinson's patients. Finally, a soft voting mechanism was employed to predict Parkinson's disease patients. The research results demonstrated that the Parkinson gut prediction method (PGPM), which utilized differential gut microbiota, performed excellently. The method achieved a mean accuracy (ACC) of 0.85, an area under the curve (AUC) of 0.92, and a receiver operating characteristic (ROC) score of 0.92. In summary, this method demonstrated excellent performance in predicting Parkinson's disease, allowing for more accurate predictions of Parkinson's disease.