Metabolomic and gut-microbial responses of earthworms exposed to microcystins and nano zero-valent iron in soil.

The earthworm-based vermiremediation facilitated with benign chemicals such as nano zero-valent iron (nZVI) is a promising approach for the remediation of a variety of soil contaminants including cyanotoxins. As the most toxic cyanotoxin, microcystin-LR (MC-LR) enter soil via runoff, irrigated surface water and sewage, and the application of cyanobacterial biofertilizers as part of the sustainable agricultural practice. Earthworms in such remediation systems must sustain the potential risk from both nZVI and MC-LR. In the present study, earthworms (Eisenia fetida) were exposed up to 14 days to MC-LR and nZVI (individually and in mixture), and the toxicity was investigated at both the organismal and metabolic levels, including growth, tissue damage, oxidative stress, metabolic response and gut microbiota. Results showed that co-exposure of MC-LR and nZVI is less potent to earthworms than that of separate exposure. Histological observations in the co-exposure group revealed only minor epidermal brokenness, and KEGG enrichment analysis showed that co-exposure induced earthworms to regulate glutathione biosynthesis for detoxification and reduced adverse effects from MC-LR. The combined use of nZVI promoted the growth and reproduction of soil and earthworm gut bacteria (e.g., Sphingobacterium and Acinetobacter) responsible for the degradation of MC-LR, which might explain the observed antagonism between nZVI and MC-LR in earthworm microcosm. Our study suggests the beneficial use of nZVI to detoxify pollutants in earthworm-based vermiremediation systems where freshwater containing cyanobacterial blooms is frequently used to irrigate soil and supply water for the growth and metabolism of earthworms.

RG-I pectic polysaccharides and hesperidin synergistically modulate gut microbiota: An in vitro study targeting the proportional relationship.

In this study, we investigated how different proportions blends of Rhamnogalacturonan-I pectic polysaccharides and hesperidin impact the gut microbiota and metabolites using an in vitro simulated digestion and fermentation model. The results indicated that both of them could modulate the gut microbiota and produce beneficial metabolites. However, their blends in particular proportions (such as 1:1) exhibited remarkable synergistic effects on modulating the intestinal microenvironment, surpassing the effects observed with individual components. Specifically, these blends could benefit the host by increasing short-chain fatty acids production (such as acetate), improving hesperidin bioavailability, producing more metabolites (such as hesperetin, phenolic acids), and promoting the growth of beneficial bacteria. This synergistic and additive effect was inseparable from the role of gut microbiota. Certain beneficial bacteria, such as Blautia, Faecalibacterium, and Prevotella, exhibited strong preferences for those blends, thereby contributing to host health through participating in carbohydrate and flavonoid metabolism.

Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic ß-cell dysfunction for T2DM management.

Insulin resistance and pancreatic ß-cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet ß-cell and enhanced pancreatic ß-cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.

Causal Effects of Gut Microbiota and Metabolites on Chronic Obstructive Pulmonary Disease: A Bidirectional Two Sample Mendelian Randomization Study.

Background: Recent evidence suggests that the gut microbiome and metabolites are intricately involved in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis, yet the precise causal relationships remain unclear due to confounding factors and reverse causation. This study employs bidirectional two-sample Mendelian Randomization (MR) to clarify these connections. Methods: Summary data from publicly available Genome-Wide Association Studies (GWAS) concerning the gut microbiome, metabolites, and COPD were compiled. The selection of genetic instrumental variables (Single Nucleotide Polymorphisms, or SNPs) for MR analysis was conducted meticulously, primarily utilizing the Inverse Variance Weighting (IVW) method, supplemented by MR-Egger regression and the Weighted Median (WM) approach. The evaluation of heterogeneity and horizontal pleiotropy was performed using Cochran's Q test, the MR-Egger intercept test, and the MR-PRESSO global test. Sensitivity analyses, including leave-one-out tests, were conducted to verify the robustness of our results. And the mediation effect of gut microbiota-mediated changes in metabolites on the causal relationship with COPD was analyzed. Results: Our study identified nine significant gut microbiota taxa and thirteen known metabolites implicated in COPD pathogenesis. Moreover, associations between the onset of COPD and the abundance of five bacterial taxa, as well as the concentration of three known metabolites, were established. These findings consistently withstood sensitivity analyses, reinforcing their credibility. Additionally, our results revealed that gut microbiota contribute to the development of COPD by mediating changes in metabolites. Conclusion: Our bidirectional Two-Sample Mendelian Randomization analysis has revealed reciprocal causal relationships between the abundance of gut microbiota and metabolite concentrations in the context of COPD. This research holds promise for identifying biomarkers for early COPD diagnosis and monitoring disease progression, thereby opening new pathways for prevention and treatment. Further investigation into the underlying mechanisms is essential to improve our understanding of COPD onset.

From gut to brain: unveiling probiotic effects through a neuroimaging perspective-A systematic review of randomized controlled trials.

The gut-brain axis, a bidirectional communication network between the gastrointestinal system and the brain, significantly influences mental health and behavior. Probiotics, live microorganisms conferring health benefits, have garnered attention for their potential to modulate this axis. However, their effects on brain function through gut microbiota modulation remain controversial. This systematic review examines the effects of probiotics on brain activity and functioning, focusing on randomized controlled trials using both resting-state and task-based functional magnetic resonance imaging (fMRI) methodologies. Studies investigating probiotic effects on brain activity in healthy individuals and clinical populations (i.e., major depressive disorder and irritable bowel syndrome) were identified. In healthy individuals, task-based fMRI studies indicated that probiotics modulate brain activity related to emotional regulation and cognitive processing, particularly in high-order areas such as the amygdala, precuneus, and orbitofrontal cortex. Resting-state fMRI studies revealed changes in connectivity patterns, such as increased activation in the Salience Network and reduced activity in the Default Mode Network. In clinical populations, task-based fMRI studies showed that probiotics could normalize brain function in patients with major depressive disorder and irritable bowel syndrome. Resting-state fMRI studies further suggested improved connectivity in mood-regulating networks, specifically in the subcallosal cortex, amygdala and hippocampus. Despite promising findings, methodological variability and limited sample sizes emphasize the need for rigorous, longitudinal research to clarify the beneficial effects of probiotics on the gut-brain axis and mental health.

Low-frequency Transcranial Magnetic Stimulation Ameliorates Anhedonic Behaviors and Regulates the Gut Microbiome in Mice Exposed to Chronic Unpredictable Mild Stress.

Objective: This paper presents a preliminary study on whether low-frequency transcranial magnetic stimulation (LF-TMS) can modulate the gut microbiota in mice with chronic unpredictable mild stress (CUMS). Methods: Mice received LF-TMS (1 Hz, 20 mT) for 28 consecutive days under chronic unpredictable mild stress (CUMS). The composition of gut microbiota of stool samples were tested. Results: CUMS caused significant changes in gut microbiotas, specifically in community diversity of gut microbiotas (P < .05). Compared with the stressed group mice, the Chao1 index (P < .05), Observed species index (P < .05), Faith's PD index (P < .05) and Shannon index (P < .05) of the LF-TMS treatment group were significantly increased. Furthermore, 1 Hz LF-TMS-treatment partially recovered chronic stress induced changes of microbiotas, such as the abundance of Chloroflexi, Actinobacteria. Conclusion: These results manifested that LF-TMS treatment can improve the anhedonic behaviors caused by CUMS in mice, which are connected with regulating the related intestinal microbial community disturbance, including species diversity, structure of gut microbiota, and species composition.

The marine environmental microbiome mediates physiological outcomes in host nematodes.

BACKGROUND: Nematodes are the most abundant metazoans in marine sediments, many of which are bacterivores; however, how habitat bacteria affect physiological outcomes in marine nematodes remains largely unknown.  RESULTS: Here, we used a Litoditis marina inbred line to assess how native bacteria modulate host nematode physiology. We characterized seasonal dynamic bacterial compositions in L. marina habitats and examined the impacts of 448 habitat bacteria isolates on L. marina development, then focused on HQbiome with 73 native bacteria, of which we generated 72 whole genomes sequences. Unexpectedly, we found that the effects of marine native bacteria on the development of L. marina and its terrestrial relative Caenorhabditis elegans were significantly positively correlated. Next, we reconstructed bacterial metabolic networks and identified several bacterial metabolic pathways positively correlated with L. marina development (e.g., ubiquinol and heme b biosynthesis), while pyridoxal 5'-phosphate biosynthesis pathway was negatively associated. Through single metabolite supplementation, we verified CoQ10, heme b, acetyl-CoA, and acetaldehyde promoted L. marina development, while vitamin B6 attenuated growth. Notably, we found that only four development correlated metabolic pathways were shared between L. marina and C. elegans. Furthermore, we identified two bacterial metabolic pathways correlated with L. marina lifespan, while a distinct one in C. elegans. Strikingly, we found that glycerol supplementation significantly extended L. marina but not C. elegans longevity. Moreover, we comparatively demonstrated the distinct gut microbiota characteristics and their effects on L. marina and C. elegans physiology. CONCLUSIONS: Given that both bacteria and marine nematodes are dominant taxa in sedimentary ecosystems, the resource presented here will provide novel insights to identify mechanisms underpinning how habitat bacteria affect nematode biology in a more natural context. Our integrative approach will provide a microbe-nematodes framework for microbiome mediated effects on host animal fitness.

The modulation of intestinal commensal bacteria possibly contributes to the growth and immunity promotion in Epinephelus akaara after feeding the antimicrobial peptide Scy-hepc.

BACKGROUND: Our previous study revealed that feeding the antimicrobial peptide (AMP) product Scy-hepc significantly enhances the growth of mariculture fish through the activation of the GH-Jak2-STAT5-IGF1 axis. However, the contribution of gut microbiota to this growth enhancement remains unclear. This study aimed to elucidate the potential mechanism involved in intestinal absorption and modulation of gut microbiota in Epinephelus akaara following Scy-hepc feeding. RESULTS: The results showed that a 35 day regimen of Scy-hpec markedly promoted the growth of E. akaara compared to groups supplemented with either florfenicol, B. subtilis, or a vector. The growth enhancement is likely attributed to alterations in microbiota colonization in the foregut and midgut, characterized by an increasing abundance of potential probiotics (Rhizobiaceae and Lysobacter) and a decreased abundance of opportunistic pathogens (Psychrobacter and Brevundimonas) as determined by 16S rRNA analysis. Additionally, similar to the effect of florfenicol feeding, Scy-hepc significantly improved host survival rate by over 20% in response to a lethal dose challenge with Edwardsiella tarda. Further investigations demonstrated that Scy-hepc is absorbed by the fish foregut (20-40 min) and midgut (20-30 min) as confirmed by Western blot, ELISA, and Immunofluorescence. The absorption of Scy-hepc affected the swimming, swarming and surfing motility of Vibrio harveyi and Bacillus thuringiensis isolated from E. akaara's gut. Moreover, Scy-hepc induced the downregulation of 40 assembly genes and the upregulation expression of 5, with the most significant divergence in gene expression between opportunistic pathogens and probiotics concentrated in their motility genes (PomA/B, MotA/B). CONCLUSIONS: In summary, this study shows that feeding AMP Scy-hepc can promote growth and bolster immunity in E. akaara. These beneficial effects are likely due to the absorption of Scy-hepc in the fish's foregut and midgut, which modulates the colonization and motility of commensal bacteria, leading to favorable changes in the composition of the foregut and midgut microbiota. Therefore, a profound understanding of the mechanisms by which antimicrobial peptides affect host gut microbiota will contribute to a comprehensive assessment of their advantages and potential application prospects as substitutes for antibiotics in fish health and improving aquaculture practices.

Sulfated fucans from algae Saccharina japonica promotes intestinal stem cell-mediated intestinal development in juvenile mouse by modulating the gut microbiota.

Intestinal development has a crucial role in the absorption of nutrients and the ability to resist infections in the early stages of life. This study utilized a 3-week-old C57BL/6 mice model to evaluate the beneficial impacts of sulfated fucans from Saccharina japonica (SJ-FUC) on the growth and development of the intestines. SJ-FUC enhanced the dimensions of the intestine, specifically the length, height of villi, and depth of the crypts. Additionally, it raised the mRNA expression of ZO-1 and Occludin, hence enhancing the structural integrity of the intestinal epithelium. SJ-FUC significantly increased mRNA expression of Lyz1, Muc2, and Math1, which resulted in the promotion of intestinal epithelial development. Furthermore, SJ-FUC augmented the mRNA levels of the ISC markers (Lgr5, Olfm4, and Ascl2). Our further research uncovered that SJ-FUC has a positive impact on the growth of beneficial bacteria, such as Akkermansia, Dubosiella, and Lactobacillus, which in turn promotes epithelial development of the intestine. In summary, our research indicates that SJ-FUC has a beneficial impact on the growth of the intestines in young mice. This is achieved by enhancing the stemness of intestinal stem cells (ISCs) and promoting the formation of the intestinal epithelium through the regulation of gut bacteria.

The Gut Health Revolution: Herbs and Dietary Phytochemicals in Balancing Gut Microbiota for Optimal Human Health.

The gut microbiota is a varied population of microorganisms that live in the human gastrointestinal system. Emerging research emphasizes the importance of this microbial ecology in general health and its influence on a variety of disorders. The review explores the synergy between herbal treatment and traditional medicine, emphasizing their cultural significance and therapeutic benefits. It delves into the intricate relationship between herbal remedies, traditional healing practices, and their sustained usage over centuries. The review highlights the pivotal role of the gut microbiota in herbal medicine, elucidating how treatments influence the gastrointestinal microorganisms, impacting overall health. Dietary phytochemicals are underscored for their significance in herbal medicine and nutritional well-being, along with the interdependence of plant extracts and botanicals. The investigation explores the molecular connections between phytoconstituents and gut microbiota, aiming to deepen the understanding of herbal medicine's tailored approach to specific health challenges. The summary concludes by emphasizing herbal treatments' unique ability to regulate gut flora, contributing to overall gastrointestinal wellbeing. In closing, the review provides a concise overview, serving as a valuable resource for integrative medicine research, with recommendations for future exploration of herbal medicine's potential in healthcare.

5-aminosalicylic acid alleviates colitis and protects intestinal barrier function by modulating gut microbiota in mice.

5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella, which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter, which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.

Combination of Lactiplantibacillus Plantarum ELF051 and Astragalus Polysaccharides Improves Intestinal Barrier Function and Gut Microbiota Profiles in Mice with Antibiotic-Associated Diarrhea.

The purpose of this study was to investigate the improvement of the intestinal barrier and gut microbiota in mice with antibiotic-associated diarrhea (AAD) using Lactiplantibacillus plantarum ELF051 combined with Astragalus polysaccharides. The amoxicillin, clindamycin, and streptomycin triple-mixed antibiotic-induced AAD models were administered with L. plantarum ELF051 or Astragalus polysaccharides or L. plantarum ELF051 + Astragalus polysaccharides for 14 days. Our findings revealed that the combination of L. plantarum ELF051 and Astragalus polysaccharides elevated the number of goblet cells and enhanced the proportion of mucous within the colon tissue. Furthermore, the expression of sIgA and IgG were upregulated, while the levels of IL-17A, IL-4, DAO, D-LA, LPS, and TGF-ß1 were downregulated. L. plantarum ELF051 combined with Astragalus polysaccharides elevated the expression of tight junction (TJ) proteins, facilitating intestinal mucosal repair via Smad signaling nodes. Furthermore, their combination effectively increased the relative abundance of lactic acid bacteria (LAB) and Allobaculum, and decreased the relative abundance of Bacteroides and Blautia. Spearman rank correlation analysis demonstrated that LAB were closely related to permeability factors, immune factors, and indicators of intestinal barrier function. In summary, the effect of combining L. plantarum ELF051 and Astragalus polysaccharides on AAD mice was achieved by enhancing intestinal barrier function and regulating the composition of the gut microbiota.

The gut microbiota of wild birds undergoing rehabilitation as a reservoir of multidrug-resistant enterococci in a metropolitan area in Brazil.

Enterococci are ubiquitous usually commensal bacteria that can act as opportunistic pathogens frequently associated with resistance to multiple antimicrobial classes. A variety of animals may carry potentially harmful enterococci. In the present work, the occurrence and characteristics of enterococci recovered from the fecal microbiota of wild birds belonging to four families (Accipitridae, Cathartidae, Falconidae and Strigidae) were investigated. Enterococci were recovered from 104 (92.0%) fecal samples obtained from 113 birds, and 260 strains were selected for additional characterization. Enterococcus faecalis was the predominant species (63.8%), followed by Enterococcus hirae (16.2%), Enterococcus faecium (11.5%), Enterococcus gallinarum (5.4%), Enterococcus avium (1.5%), Enterococcus casseliflavus (0.8%), and Enterococcus raffinosus and Enterococcus cecorum (0.4% each). Major percentages (11.9% 75.0%) of nonsusceptibility were observed to quinolones (particularly to enrofloxacin), erythromycin, rifampin, nitrofurantoin, tetracycline and streptomycin. Gentamicin and ampicillin resistances (13.3% each) were only detected among E. faecium. A total of 133 (51.2%) strains were MDR, showing a large variety of MDR profiles, composed by simultaneous resistance encompassing 3 to 12 antimicrobials. MDR strains were found in 68.2% of the birds. Antimicrobial resistance was associated with the presence of the aac(6')-aph(2″)-Ia, aph(2″)-Id, ant(6)-Ia, ant(9)-Ia, ant(9)-Ib, tet(M), tet(L), tet(S), erm(B), mef(A/E), msrC, and vat(D) genes. The most common virulence genes were efaA, gelE, ace, eeP, and asa1. PFGE analysis revealed a large genetic diversity among most of the strains. MLST performed for 35 E. faecalis strains revealed 23 different STs, whereas 14 STs were found among 18 E. faecium strains. Hospital-associated lineages ST22, ST25, ST56, ST1274 were identified. The results show that the wild birds investigated can carry a diversity of potentially hazardous enterococcal strains displaying multiple antimicrobial resistance and virulence genes, reinforcing the assumption that these animals provide an important target to monitor the circulation of microorganisms that deserve consideration under the One Health perspective.

Gut microbiota of miR-30a-5p-deleted mice aggravate high-fat diet-induced hepatic steatosis by regulating arachidonic acid metabolic pathway.

BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) often exhibit hepatic steatosis and dyslipidemia. Studies have shown that intestinal microorganisms are closely related to the occurrence of NAFLD and atherosclerosis. Our previous study has underscored the protective role of microRNA-30a-5p (miR-30a-5p) against atherosclerosis. METHODS AND RESULTS: In the present study, we aimed to elucidate the effect and underlying mechanism of the intestinal microorganisms of miR-30a-5p knockout (KO) mice on NAFLD. Our findings demonstrated that KO exacerbated high-fat diet (HFD)-induced hepatic steatosis and disrupted liver function, as evidenced by elevated levels of total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, and total bile acids in serum. Fecal microbiota from HFD-fed KO mice induced hepatic steatosis, dyslipidemia, and higher levels of enzymes indicative of liver damage in wild-type mice. Remarkably, KO mice significantly intensified the above effects. 16s rDNA sequencing and metabolomics of the intestinal microbiota in the HFD-treated KO and WT mice showed that the loss of miR-30a-5p resulted in intestinal microbiota imbalance and was highly related to the arachidonic acid metabolic pathway. Targeted metabolomic in the liver tissues unveiled upregulation of COX-related (PGF2a, 8-iso-PGF2a and PGF2) and LOX-related (LTB4, LTD4, 12S-HETE and 15S-HETE) factors in HFD-treated KO mice. Immunohistochemistry and transcriptional analyses showed that miR-30a-5p affected arachidonic acid metabolism through the LOX/COX pathways. Besides, COX/LOX pathways and hepatic steatosis were reversed after reintroducing miR-30a-5p in HFD-treated KO mice. CONCLUSIONS: This study reveals the pivotal mechanism by which miR-30a-5p and intestinal microbes regulate hepatic steatosis and abnormal lipid metabolism, offering promising avenues for NAFLD and atherosclerosis therapeutics. HIGHLIGHTS: MiR-30a-5p deletion aggravated hepatic steatosis and lipid disorder induced by an HFD in mice. Gut microbiota participated in the regulation of hepatic steatosis in the context of miR-30a-5p. Gut microbiota metabolism-related arachidonic acid metabolic pathway contributed to miR-30a-5p-regulated hepatic steatosis and lipid disorder. Reintroducing miR-30a-5p reversed hepatic steatosis and arachidonic acid metabolism disorder caused by HFD and miR-30a-5p deletion.

Global Insights and Key Trends in Gut Microbiota Research for Premature Infants: A Bibliometric and Visualization Study.

Background: Premature infants, defined as those born before 37 weeks of gestation, face numerous health challenges due to their underdeveloped systems. One critical aspect of their health is the gut microbiota, which plays a vital role in their immune function and overall development. This study provides a comprehensive bibliometric analysis of research trends, influential contributors, and evolving themes in the study of gut microbiota in premature infants over the past two decades. Methods: We conducted a bibliometric analysis using the Web of Science Core Collection database, covering publications from January 1, 2004, to June 17, 2024. We employed VOSviewer, the R package "bibliometrix", and Citespace for data visualization and analysis, focusing on co-authorship, co-citation, and keyword co-occurrence networks. Results: The temporal analysis revealed a significant increase in research output on gut microbiota in premature infants, particularly in the last decade. Early research primarily focused on characterizing the gut microbiota of premature infants, identifying less diversity and a higher prevalence of pathogenic bacteria compared to full-term infants. Key research themes identified include probiotics, necrotizing enterocolitis (NEC), and breastfeeding. Probiotic studies highlighted the potential of strains like Bifidobacterium and Lactobacillus in reducing NEC and sepsis incidences. Breastfeeding research consistently showed the benefits of human milk in fostering a healthier gut microbiota profile. Co-authorship and co-citation analyses identified key contributors and influential studies, emphasizing strong international collaborations, particularly among researchers from the United States, China, and European countries. Conclusion: This bibliometric analysis underscores the growing recognition of the gut microbiota's crucial role in the health of premature infants. The field has seen significant advancements, particularly in understanding how interventions like probiotics and breastfeeding can modulate gut microbiota to improve health outcomes. Continued research and international collaboration are essential to further unravel the complexities of gut microbiota in premature infants and develop effective therapeutic strategies.

Integrated metabolomics and gut microbiota analysis to explore potential mechanism of Qi-Huo-Yi-Fei formula against chronic obstructive pulmonary disease.

Metabolic disorders and gut microbiota dysbiosis contribute to the complicated pathology of chronic obstructive pulmonary disease (COPD). Qi-Huo-Yi-Fei formula (QHYFF) is a Chinese medicine prescription for COPD treatment and has showed beneficial clinical effects, but the underlying mechanism remains elusive. This study integrated metabolomics and gut microbiota analysis to explore potential mechanism of QHYFF against COPD. The therapeutic effects of QHYFF were evaluated using a murine model of COPD induced by cigarette smoke and lipopolysaccharide. QHYFF effectively improved pulmonary function, suppressed inflammation, and relieved lung pathological changes. Serum and urine metabolomics analysis identified 19 differential metabolites, such as L-tyrosine, epinephrine, dopamine, hypotaurine, citric acid, L-tryptophan and indoleacrylic acid, involving tyrosine metabolism, taurine and hypotaurine metabolism, citrate cycle and tryptophan metabolism. QHYFF also enriched Bifidobacterium, Blautia, Faecalibaculum and Parasutterella. Moreover, Spearman's correlation analysis showed that discriminative metabolites and bacteria were closely correlated with efficacy indices. The findings indicated that QHYFF could be an effective therapeutic measure against COPD by regulating metabolism and gut microbiota.

Flavonoids, gut microbiota and cardiovascular disease: Dynamics and interplay.

Cardiovascular disease (CVD) remains the leading cause of global morbidity and mortality. Extensive efforts have been invested to explicate mechanisms implicated in the onset and progression of CVD. Besides the usual suspects as risk factors (obesity, diabetes, and others), the gut microbiome has emerged as a prominent and essential factor in the pathogenesis of CVD. With its endocrine-like effects, the microbiome modulates many physiologic processes. As such, it is not surprising that dysbiosis-by generating metabolites, inciting inflammation, and altering secondary bile acid signaling- could predispose to or aggravate CVD. Nevertheless, various natural and synthetic compounds have been shown to modulate the microbiome. Prime among these molecules are flavonoids, which are natural polyphenols mainly present in fruits and vegetables. Accumulating evidence supports the potential of flavonoids in attenuating the development of CVD. The ascribed mechanisms of these compounds appear to involve mitigation of inflammation, alteration of the microbiome composition, enhancement of barrier integrity, induction of reverse cholesterol transport, and activation of farnesoid X receptor signaling. In this review, we critically appraise the methods by which the gut microbiome, despite being essential to the human body, predisposes to CVD. Moreover, we dissect the mechanisms and pathways underlying the cardioprotective effects of flavonoids.

Combination of lipopolysaccharide and polygalacturonic acid exerts antitumor activity and augments anti-PD-L1 immunotherapy.

Polygalacturonic acid (PGA) restored the alpha-diversity of gut microbiota and promoted T cells infiltration in tumors. Here, we investigated whether oral administration of PGA could improve the anti-cancer effect of lipopolysaccharide-encapsulated PLGA-PEG-PLGA (LPS/PPP) in mice bearing CT26 tumors. Hydrogels with rapid thermogelling properties can achieve localized and controlled release of LPS, thus retaining the anti-cancer effect of LPS and avoiding a robust inflammatory storm. LPS/PPP promoted M1 macrophage polarization, TLR4 expression, and phagocytosis in tumors. The combination of PGA and LPS/PPP (PGA_LPS) notably repressed CT26 tumor growth and the inhibition rate reached 67.6 %. PGA_LPS triggered the recruitment of helper and cytotoxic T cells, IFN-γ level, decreased the proportion of immunosuppressive regulatory T cells. PGA_LPS also restored the beta-diversity of gut microbiota and increased short chain fatty acids abundance (butyric acid, 608.93 % vs. model group, P < 0.01). PGA_LPS followed by αPD-L1 resulted in obvious inhibition of both CT26 and 4T1 tumor growth, promoted cleaved-caspase 3 and Bax expression, T cell responses and the rescue of T cells exhaustion. These results confirmed that PGA_LPS reinforced the anticancer effect of αPD-L1, probably by reshaping the tumor microenvironment and intestinal flora, which sheds light on the combination approach to intensify the effect of immune checkpoint inhibitors.

Increasing degree of substitution inhibits acetate while promotes butyrate production during in vitro fermentation of citric acid-modified rice starch.

Citric acid-modified starch functions as a resistant starch, while the combined effects of its fine molecular structure and degree of substitution on gut microbiota are not well understood. To this end, citric acid-modified starches with varying degrees of substitution were synthesized from rice starches with distinct molecular structures and their impact on gut microbiota composition and short-chain fatty acid (SCFA) production was analyzed. Notably, rice starch with a higher degree of substitution significantly reduced acetate production, while promoting butyrate production. Correlation analysis further suggested that amylopectin chains with 12 < DP ≤ 36 and amylose chains with 100 < DP ≤ 500 alter the growth of Faecalibacterium_prausnitzii and Bacteroides_vulgatus, consequentially determining the production of SCFAs. Collectively, these findings indicate that citric acid-modified rice starch with different degrees of substitution can target specific gut bacteria and SCFA production, thus conferring beneficial impact on human health.

Fibroblast growth factor 1 (FGF1) improves glucose homeostasis, modulates gut microbial composition, and reduces inflammatory responses in rainbow trout (Oncorhynchus mykiss) fed a high-fat diet.

High-fat diets (HFDs) are widely used in aquaculture due to their lipid and protein-conserving effects, thereby reducing feed costs. However, prolonged feeding of HFD often leads to metabolic disorders in fish, such as disruption of hepatic lipid homeostasis, liver injury, and disruption of glucose homeostasis. Fibroblast growth factor 1 (FGF1) plays an essential role in controlling glucose levels in the body and dampening immune reactions. However, its impact on teleosts remains poorly researched. The therapeutic potential of recombinant FGF1 (rFGF1) was examined in a 6-week culture experiment involving rainbow trout (Oncorhynchus mykiss) that were fed an HFD. The results revealed that rFGF1 significantly reduced serum glucose levels and hepatic PEPCK and G6PC activities, but improved hepatic glycogen (P < 0.05), compared to the HFD + PBS group. Further experiments indicated that the inhibitory effect of rFGF1 on hepatic gluconeogenesis was mediated by the cAMP signaling pathway and was dependent on the high expression of PDE4. In addition, rFGF1 increased hepatic glycogen content, which involves the AKT-GSK3ß axis. Despite this increase, rFGF1 did not lead to glycogen storage disease, as shown by reduced hepatic inflammation as a result of decreased GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), and elevated SOD (superoxide dismutase) in the rFGF1-treated group, accompanied by decreased il-1ß, il-6, and xbp-1, and elevated nrf2 and number of hepatocyte autophagosomes. Alterations in gut microbes and short-chain fatty acids (SCFAs) were noted, indicating that rFGF1 caused a notable rise in intestinal Lactobacillus, acetic acid, and butyric acid levels. This study investigated the molecular mechanisms of rFGF1 on glucose metabolism and inflammatory responses in an HFD-fed rainbow trout model, providing new insights to improve the regulation of glucose metabolism in carnivorous fish.