Search Results (104)

Research on autism spectrum disorders (ASDs) has so far focused primarily on the gut–brain axis, whereas the role of the gut–liver axis remains insufficiently explored. The aim of this study was to evaluate whether microbiota derived from girls with ASD induces dysbiotic changes in gut microbiota composition and leads to alterations in gut–liver axis processes in pseudo-germ-free (PGF) BALB/c mice. We also examined whether these processes could be modulated by altering the gut microbiota using the probiotic strains Lactiplantibacillus plantarum CCM 7512 and Limosilactobacillus reuteri CCM 8617 in combination with ground flaxseed (Linum usitatissimum L.) as a source of omega-3 polyunsaturated fatty acids and fermentable fiber. Colonization with fecal microbiota derived from girls with ASD resulted in dysbiotic changes in the composition of the cecal microbiota, characterized by an increased relative abundance of Escherichia–Shigella, Fusobacterium, Alistipes, and the Ruminococcus gnavus group. These changes were accompanied by impaired intestinal mucosal integrity, altered metabolomic pathways related mainly to aromatic amino acids and lipid metabolism, increased hepatic immunoreactivity of iNOS and COX-2, and elevated activity of the liver-specific LDH-5 isoenzyme. These results suggest that synbiotic intervention contributed to remodeling of the cecal microbiota composition, restoration of intestinal epithelial integrity, and modulation of metabolomic pathways, which was reflected by reduced immunoreactivity of iNOS and COX-2 in liver tissue and decreased activity of the LDH-5 isoenzyme. These findings support the role of microbiota-mediated metabolic processes in communication between the gut and the liver within the gut–liver axis. Full article

Angiotensin-converting enzymes (ACE and ACE2) are key components of the renin–angiotensin–aldosterone system (RAAS) and are present in the gastrointestinal tract and intestinal content, preserving their catalytic activity, and may interact with the gut microbiota. The present study aimed to determine the origin of fecal ACE and ACE2 activity. Fecal pellets from germ-free, ACE and ACE2 knockout (KO) mice, and from the corresponding controls were analyzed using fluorimetric enzyme activity assays. ACE activity was assessed using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates; ACE2 activity was assessed using Mca-APK (Dnp), with and without the ACE2 inhibitor MLN-4760. Germ-free mice showed increased fecal ACE and ACE2 activity compared to controls. ACE2-KO mice lacked fecal ACE2 activity, whereas ACE activity was unaffected. In ACE-KO mice, fecal ACE activity was reduced, but not abolished, while ACE2 activity remained similar to controls. In ACE C- and N-domain KO mice, ACE activity was similar to controls, and inhibition with captopril completely abolished fecal ACE activity using Hippuryl-His-Leu, but not Z-Phe-His-Leu, in those animals. These findings indicate that fecal ACE and ACE2 activity results from combined intestinal shedding and microbiota-related mechanisms, supporting a modulatory role of the gut environment on luminal RAAS activity. Full article

Cheese is a complex fermented dairy food containing bioactive nutrients and microorganisms that can influence host physiology. However, most existing evidence of its health effects derives from observational studies or investigations of isolated components rather than the whole food matrix. The present study examined the impact of low-fat Cheddar cheese as a whole food on the gut microbiota using a human microbiota–associated (HMA) mouse model. Germ-free C57BL/6 mice were colonized with human fecal microbiota and randomly assigned to either a control diet or a diet supplemented with low-fat Cheddar cheese (7.5% w/w) for six weeks. Fecal samples were collected longitudinally and analyzed by 16S rRNA gene (V3–V4 region) amplicon sequencing. Human microbiota transplantation successfully established a stable, human-like gut microbial community in the mice. Cheese supplementation significantly increased alpha diversity (Shannon and Chao1 indices) and altered microbial composition, characterized by a higher relative abundance of Firmicutes and a reduction in Bacteroidetes (p < 0.001). At the genus level, Lactococcus and Streptococcus were enriched in cheese-fed mice, reflecting potential viable transfer of cheese-derived lactic acid bacteria. These findings provide experimental evidence that low-fat Cheddar cheese can beneficially influence the human-derived gut microbiota in an animal model and highlight the need for further clinical research to validate these effects in humans. Full article

Background/Objectives: The pathogenesis of ulcerative colitis (UC) is complex, and there is an urgent need for effective therapeutic agents with low side effects. Recent studies highlight the critical roles of abnormal bile acid (BA) metabolism and gut microbiota dysbiosis in UC progression. However, there is a significant knowledge gap about the relation between BA and gut microbiota. The BA derivative T3K exerts good anti-UC effect, and its mechanism is still unknown. In this study, we investigate how its anti-UC mechanism is involved in the modulation of the gut microbiota-BA axis and BA metabolism. Methods: Gene expression microarray GSE92415 of UC from the Gene Expression Omnibus was used to analyze BA metabolism. DSS-induced colitis mouse model, Caco-2 and IEC6 cells were used to confirm the anti-UC of T3K using intestinal permeability assay with FITC, Western-blot, immunohistochemical staining, immunofluorescenc and so on in vitro and in vivo. The changes in bile acid and microbiota were measured by 16S rRNA sequencing and bile acid analysis combined with pseudo-germ-free (PGF) models and fecal microbiota transplantation (FMT). Results: T3K demonstrated strong therapeutic effects, including reduced weight loss, lower disease activity index (DAI), and increased colon length. T3K also enhanced the expression of Occludin and Mucin2, and restored gut barrier integrity. Furthermore, T3K improved intestinal dysbiosis and abnormal BA metabolism in colitis mice. Through PGF models and FMT, we confirmed that T3K modulates BA metabolism via the gut microbiota. T3K specifically promotes the growth of beneficial bacteria, such as Akkermansia muciniphila, increases levels of hydrophilic BAs like muricholic acid (MCA), lithocholic acid (LCA) and its derivatives isoLCA and then repairs damaged intestinal mucosa. Conclusions: Bile acid derivative T3K, as a potential anti-UC candidate, effectively restores gut barrier integrity and then ameliorates colitis by improving gut microbiota composition and regulating BA metabolism, including increasing hydrophilic BAs. Full article

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis (UC), are characterized by chronic gastrointestinal inflammation and involve complex interactions of genetic, environmental, and immune factors. Enterococcus faecalis, a gut commensal bacterium, has been implicated in IBD pathogenesis. This study investigated the effects of monocolonization with a UC-derived E. faecalis strain on acute dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) mice, focusing on epithelial injury, inflammatory markers, hematologic indices, and bacterial translocation. In DSS-treated mice, monocolonization was associated with modest and mixed effects, including a higher colitis-related disease activity score, reduced anemia, increased fecal albumin and a trend towards reduced fecal calprotectin. Despite translocation of E. faecalis to mesenteric lymph nodes, no systemic dissemination was observed. Histological analysis revealed broadly similar inflammatory patterns between DSS-treated groups, with slightly more epithelial injury observed in colonized mice. These findings suggest that E. faecalis may influence discrete aspects of DSS injury in a strain-dependent and context-specific manner, rather than broadly altering overall disease severity. This study highlights the utility of GF models for examining strain-specific host–microbe interactions and underscores that individual bacterial isolates may exert heterogeneous and selective effects on acute colitis. Further research is needed to elucidate these complex mechanisms. Full article

Background: Agents with free radical-scavenging functions may act as radiation modifiers, protectors, or mitigators. Methods: We investigated whether supplementation with resveratrol (RSV) in mice, at different times after the beginning of X-irradiation, may influence sperm count and quality during the irradiation and recovery. Results: Irradiation importantly decreased the sperm count. RSV supplemented with 1 Gy since 24 h increased sperm count. The combination of low doses increased, whereas the combination of high doses reduced DNA damage. Coadministration of two high doses since the eighth day significantly increased DNA damage and slightly increased sperm count. The supplementation of RSV during recovery was toxic to irradiated males. The sperm parameters were a little better in the absence of RSV. The degree of DNA injury of germ cells was importantly lower in groups combined with 1 Gy. Conclusions: Resveratrol counteracted the radiation-induced death of germ cells and improved the sperm count. RSV may function as radioprotector (before or during exposure) and radiomitigator (after exposure) of lethal effects in male gametes. The combination of high doses of irradiation with RSV over 24 h mitigated DNA damage. Contrarily, supplementation during recovery is not recommended since it may be toxic during long-lasting irradiation. Full article

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically characterized by impaired social communication. Previous reports have postulated gut microbiota to be an important non-genetic factor affecting ASD-like phenotypes in mice, as germ-free (GF) mice show impaired social communication. Results: In this study, we identified hippuric acid (HA) as a metabolite generated via a gut microbiome-dependent mechanism that plays a role in the acquisition of social behavior during mouse development. We discovered that oral or intraperitoneal HA administration to GF mice normalizes their social behavior. Furthermore, HA administration restored oxytocin expression in the hypothalamic paraventricular nucleus and secretin expression in the subfornical organ, suggesting that HA may activate the secretin–oxytocin system to influence the social behavior of mice. Conclusions: These findings indicate that HA may serve as an important gut microbiome-dependent mediator affecting the brain mechanisms involved in regulating social behavior. Full article

This study explored the potential therapeutic effect and possible mechanism of Atractylodes macrocephala Koidz. Polysaccharide (AP) on pirarubicin chemotherapy-induced depression (CID) in breast cancer mice. This study utilized a variety of techniques to explore the potential of AP in mitigating behavioral abnormalities and elucidate the role of gut microbiota regulation in its therapeutic effects on chemotherapy in breast cancer mice. These included a chemotherapy mouse model, behavioral assessments, histological analysis using hematoxylin and eosin staining, ultrastructural examination, enzyme-linked immunosorbent assays, 16S rDNA sequencing, metabolomic profiling, Western blot analysis, and a pseudo-germ-free animal model. Oral administration of AP significantly improved depression-like behaviors in breast cancer chemotherapy mice while also reducing neuronal damage and inflammation in the hippocampus. AP prevented ferroptosis of intestinal tissues caused by chemotherapy and had a repairing effect on the intestinal barrier damage of chemotherapy-induced mice. Additionally, AP enhanced gut microbiota composition and altered intestinal metabolites in chemotherapy-treated mice. It notably decreased the abundance of certain microbes, such as Bacteroidaceae, Lachnospiraceae, Oscillospiraceae, and Clostridium, while significantly increasing the abundance of Alistipes. Moreover, AP efficiently modulated intestinal metabolites, including glycocholic acid, L-Phenylalanine, and palmitoylcarnitine. More importantly, depletion of gut microbiota through antibiotics diminished the effectiveness of AP. Our results suggest that AP alleviates depression-like behaviors in chemotherapy-treated mice by regulating the gut microbiota and microbial metabolism, as well as suppressing ferroptosis in intestinal tissues. Full article

Background: Type 2 diabetes (T2D) has become a serious global public health concern. Liubao tea (LBT) has demonstrated beneficial effects on gut microbiota and glucose-lipid metabolism, holding promising therapeutic potential for T2D; however, its underlying mechanisms remain unclear. This study aims to elucidate the potential mechanisms of Liubao tea extract (LBTE) against T2D. Methods: LC-MS technology was used to identify the chemical components of LBTE and combined with network pharmacology and molecular docking to screen its potential active ingredients and targets for improving T2D. Therapeutic efficacy was assessed in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice via serum biochemical analyses and histopathological examinations. Serum metabolomics, 16S rRNA sequencing, quantification of short-chain fatty acids (SCFAs), quantitative real-time PCR (qPCR), and antibiotic-treated pseudo-germ-free models were employed to elucidate the underlying mechanisms. Results: LBTE effectively reduced blood glucose levels and improved lipid metabolism, primarily by promoting hepatic glycogen synthesis and suppressing glycerophospholipid synthesis. LBTE also alleviated hepatic inflammation by modulating inflammatory cytokine expression. Additionally, LBTE reshaped the gut microbiota profiles by decreasing harmful bacteria and increasing SCFA-producing bacteria, resulting in elevated fecal SCFAs. SCFAs contributed to improving hepatic metabolism and inflammation, enhancing intestinal barrier function. Notably, these effects were abolished by antibiotic-induced microbiota depletion, confirming the microbiota-dependent mechanism of LBTE. Quercetin, luteolin, genistein, and kaempferol were considered as potential active ingredients contributing to the antidiabetic effects of LBTE. Conclusions: These findings provide novel perspectives on the viability of LBTE as a complementary strategy for T2D prevention and management. Full article

Polyphenols are compounds derived from plant-based food possessing numerous biological activities, including inhibiting oxidative stress, suppressing inflammation, and regulating gut microbiota. In this study, we investigated the effects of quinic acid, a phenolic acid from millet, on the regulation of gut microbiota and intestinal inflammation and further discussed the possible mechanism. The results showed that quinic acid could improve the microbiota composition of the feces of patients with inflammatory bowel disease (IBD) by in vitro anaerobic fermentation by increasing the abundance of beneficial genera including Bifidobacterium, Weissella, etc., and decreasing that of harmful genera like Escherichia-Shigella. Quinic acid treatment could alleviate the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice, maintain the intestinal barrier, down-regulate the expression of inflammatory factors such as IL-1β and TNF-α, and inhibit the activation of the MyD88/NF-κB signaling pathway. In addition, quinic acid also improved the diversity of gut microbiota in mice with colitis. Furthermore, pseudo-germ-free colitis mice proved that the effect of quinic acid on intestinal inflammation was diminished after removing most gut microbiota by antibiotic treatment, suggesting that gut microbiota play important roles during the regulation of colitis by quinic acid. In a word, our study verified the regulatory effects of quinic acid on intestinal inflammation, depending on gut microbiota regulation and NF-κB signaling suppression. Full article

Background: Low-dose antibiotic contamination in animal feed is a persistent global food safety challenge. Transient early-life exposure to low-dose penicillin (LDP) is known to induce metabolic syndrome (MetS) in adult mice, but the underlying mechanisms are unclear. Introduction: This study investigated the role of gut microbiota (GM) and intestinal immunity in mediating the long-term metabolic effects of early-life LDP exposure. Methods: Mice were exposed to LDP transiently during early life. GM composition was analyzed. Intestinal IgA responses were quantified. Bacterial encroachment, systemic and adipose tissue inflammation, and diet-induced MetS were assessed. Germ-free (GF) mice received GM transplants from LDP-exposed or control mice to test causality and persistence. Results: Early-life LDP exposure significantly disrupted GM composition, particularly in the ileum, in 30-day-old mice. These GM alterations caused persistent suppression of intestinal IgA responses, evidenced by reduced IgA-producing cells and sIgA levels. This suppression was constrained to early-life exposure: transferring LDP-modified GM to GF mice produced only a transient reduction in fecal sIgA. The LDP-induced sIgA reduction decreased IgA binding of bacteria, leading to increased bacterial encroachment and systemic and adipose tissue inflammation. These pathological changes exacerbated diet-induced MetS. Discussion: Our findings demonstrate that early-life LDP exposure induces persistent intestinal IgA deficiency through lasting GM alterations initiated in early development. This deficiency drives bacterial encroachment, inflammation, and ultimately exacerbates MetS. Conclusions: The exacerbation of diet-induced metabolic syndrome by early-life LDP exposure occurs through an intestinal sIgA-dependent pathway triggered by persistent GM disruption. This highlights a critical mechanism linking early-life antibiotic exposure, gut immune dysfunction, and long-term metabolic health, with significant implications for food safety. Full article

The human gastrointestinal tract is estimated to be populated by 38 trillion bacteria from almost 1000 different species. The dominant phyla are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. However, the diversity and amount of gut microbiota depends on various factors. The importance of gut microbiota is increasingly noticed due to the influence of bacteria on energy homeostasis, the immune system, general health, and metabolism. Bariatric surgery is the mainstay treatment for patients with obesity. Two of the most common mechanisms are reducing gastric volume and decreasing ghrelin secretion. This literature review aims to depict the diverse impact of different bariatric procedures on gut microbiota. The original research papers were collected from the PubMed, Cochrane, and Elsevier databases. This literature review is focused on human studies. However, several references include animal models, specifically rats and germ-free mice. The findings suggest that bariatric surgery causes changes in the diversity of gut microbiota. However, the specificity of the changes depends on the type of bariatric surgery. The Firmicutes/Bacteroidetes ratio is elevated in the groups of patients with obesity compared to lean individuals. Bariatric surgery lowers the ratios impact on metabolism and energy absorption. Gut microbiota produces short-chain fatty acids, of which butyrate is responsible for strengthening the gut barrier, and acetate is correlated with fat deposition and lipogenesis. Moreover, changes in short-chain fatty acids influence insulin resistance and inflammation. In conclusion, bariatric surgery impacts gut microbiota, resulting in metabolic changes in patients, and the need for further study regarding long-term microbiota alterations post-operation is notable. Full article

Cocaine use disorder remains a major global health concern, with growing evidence that the gut microbiome modulates drug-related behaviors. This study examines the microbiome’s role in cocaine-induced psychomotor activation and context-dependent reward responses using germ-free (GF) and antibiotic-treated (ABX) models. In GF mice, the absence of a microbiome blunted cocaine-induced psychomotor activation (p = 0.013), which was restored after conventionalization. GF mice also showed reduced cocaine-conditioned place preference (CPP) (p = 0.002), which normalized after conventionalization. Dopaminergic function, critical for psychomotor responses and reward, was microbiome-dependent, with increased dopamine levels (p = 0.009) and normalized turnover ratios after conventionalization. In the ABX model, microbiome depletion reduced both cocaine-induced locomotion and CPP responses (p ≤ 0.009), further supporting the role of gut microbes in modulating psychomotor and reward behaviors. ABX-treated mice also showed significant declines in microbial diversity, shifts in bacterial structure, and dysregulation in metabolic, immune, and neurotransmitter pathways (p ≤ 0.0001), including alterations in short-chain fatty acids and gamma-aminobutyric acid metabolism. These findings highlight the gut microbiome’s critical role in regulating cocaine’s psychomotor and rewarding effects, offering insights into potential therapeutic strategies for cocaine use disorder. Full article

Enterotoxigenic Escherichia coli (ETEC) is a major pathogen causing diarrhea in humans and animals, with increasing antimicrobial resistance posing a growing challenge in recent years. Lytic bacteriophages (phages) offer a targeted and environmentally sustainable approach to combating bacterial infections, particularly in eliminating drug-resistant strains. In this study, ETEC strains were utilized as indicators, and a stable, high-efficiency phage, designated vB_EcoM_JE01 (JE01), was isolated from pig farm manure. The genome of JE01 was a dsDNA molecule, measuring 168.9 kb, and a transmission electron microscope revealed its characteristic T4-like Myoviridae morphology. JE01 effectively lysed multi-drug-resistant ETEC isolates. Stability assays demonstrated that JE01 retained its activity across a temperature range of 20 °C to 50 °C and a pH range of 3–11, showing resilience to ultraviolet radiation and chloroform exposure. Furthermore, JE01 effectively suppressed ETEC adhesion to porcine intestinal epithelial cells (IPEC-J2), mitigating the inflammatory response triggered by ETEC. To investigate the in vivo antibacterial efficacy of phage JE01 preparations, a diarrhea model was established using germ-free mice infected with a drug-resistant ETEC strain. The findings indicated that 12 h post-ETEC inoculation, intragastric administration of phage JE01 significantly reduced mortality, alleviated gastrointestinal lesions, decreased ETEC colonization in the jejunum, and suppressed the expression of the cytokines IL-6 and IL-8. These results demonstrate a therapeutic benefit of JE01 in treating ETEC-induced diarrhea in mice. Additionally, a fluorescent phage incorporating red fluorescent protein (RFP) was engineered, and the pharmacokinetics of phage therapy were preliminarily assessed through intestinal fluorescence imaging in mice. The results showed that the phage localized to ETEC in the jejunum rapidly, within 45 min. Moreover, the pharmacokinetics of the phage were markedly slowed in the presence of its bacterial target in the gut, suggesting sustained bacteriolytic activity in the ETEC-infected intestine. In conclusion, this study establishes a foundation for the development of phage-based therapies against ETEC. Full article

As an extraordinarily diverse group of bacteria, lactobacilli are now classified into several genera, many of which still include “Lactobacillus” in their names. Despite their names, this group of lactic acid bacteria comprises microorganisms that are crucial for human health, especially during the early development of the human microbiota and immune system. The interactions between lactobacilli and components of the mucosal immunity lead to its shaping and development, which is possibly considered a prime mover in the advancement of the human immune system. Although much of the evidence backing the pivotal role of lactobacilli in maintaining human health comes from studies on probiotics aiming to elucidate the mechanisms of their functional activities and studies on mucosal immunity in germ-free mice, it is justifiable to extend observations on the properties of the individual probiotic Lactobacillus that are related to health benefits onto other strains sharing common characteristics of the species. In this review, we will discuss the acquisition, presence, and functions of lactobacilli in different human microbiota throughout their whole life, including those arising in the amnion and their interactions with mucosal and immune cells. Examples of immune system modulation by probiotic lactobacilli include their colonic competition for available nutrients, interference with colonization sites, competition for binding sites on gut epithelial cells, bacteriocin production, reduction of colonic pH, and nonspecific stimulation of the immune system. Full article