Gut Microbiota Composition Research Articles

Arecoline Alleviates Depression via Gut-Brain Axis Modulation, Neurotransmitter Balance, Neuroplasticity Enhancement, and Inflammation Reduction in CUMS Mice.

This study evaluated the antidepressant effects of arecoline, a bioactive alkaloid derived from areca nuts, using a mouse model of depression induced by chronic unpredictable mild stress. Arecoline treatment significantly alleviated depression-like behaviors, including anxiety, anhedonia, and despair, as evidenced by behavioral tests. Mechanistically, arecoline restored serotonin and norepinephrine levels in the brain and serum, reduced pro-inflammatory markers such as IL-1β and LPS in both serum and colon, and enhanced hippocampal neuroplasticity through increased BDNF and PSD-95 expression. Moreover, arecoline modulated gut microbiota composition, particularly enriching beneficial species like Bifidobacterium pseudolongum and Ligilactobacillus murinus, and regulated serum metabolites associated with tryptophan metabolism, neurotransmitter synthesis, and oxidative stress. These findings demonstrate that arecoline exerts its antidepressant effects via a multitargeted approach involving the gut-brain axis, neurotransmitter modulation, and neuroplasticity enhancement. This study highlights arecoline as a promising therapeutic candidate for depression, emphasizing its potential to address both central and peripheral mechanisms.

Abstract 2215: Age and indoleamine 2,3-dioxygenase 1 (IDO1) interact to affect gut microbiome homeostasis in subjects with glioblastoma

Objective: This study aimed to determine how age and IDO1 interact to affect the gut microbiome, microbial metabolite levels, and survival outcomes in subjects undergoing IDO1-targeted immunotherapy against glioblastoma (GBM). Methods: Serum and colon contents from younger 16-20- or older 92-118-week-old wild-type (WT), IDO1 knockout (IDO1-KO), and IDO1 enzyme null (IDO1-H350A) mice were analyzed for 16S rRNA gut microbiome composition and microbial-derived aromatic amino acid metabolites via LC/MS/MS. Fecal samples from younger 7-8 or older 81-85 week-old WT mice with intracranial syngeneic GL261 GBM cells treated with or without brain radiation (RT) and PD-1 mAb were also analyzed. Fecal and plasma samples from 12 newly diagnosed IDHwt/MGMT promoter unmethylated GBM patients who received RT plus PD-1 mAb and IDO enzyme inhibitor were also analyzed. Results: Young and old IDO1-KO and IDO1-H350A mice demonstrated a unique gut microbiome signature with an elevated abundance of Bifidobacterium and Helicobacter (p<0.05) and a reduced abundance of Ventriosum and Sireaum compared to WT mice (p<0.001). Prevotellaceae, Muribaculum, Alistipes, Enterohabdus, Clostridia, and Akkermansia were different in IDO1-KO and IDO1-H350A mice compared to WT - but only in older mice. Serum microbiome-derived aryl-lactates phenyllactate (PLA), indolelactate (ILA), and 4-hydroxyphenyllactate (4HPLA) were increased in IDO1-KO mice compared to WT and IDO1-H350A mice (p<0.001) - but only in older mice. Older WT mice with GL261 GBM showed lower fecal aryl-lactates (PLA, 4HPLA, and ILA) compared to younger counterparts. Treatment with RT + PD-1 mAb also showed decreased serum indole propionic acid (IPA) levels in young but not old mice with GL261 GBM (p<0.05). Analyses from GBM patient baseline fecal samples revealed that higher abundance of Massilioclostridium coli, GGB3819-SGB5184, Dysosmobacter welbionis, and Phocaeicola plebeius was associated with longer survival (p<0.004), while higher levels of fecal ILA and lower levels of plasma IPA also correlated with elongated survival (p<0.04 and p<0.01 respectively). Combined treatment of RT + PD-1 mAb + IDO1 inhibitor decreased plasma IPA when compared to baseline (p<0.01). Conclusions: IDO1 possesses both enzyme- and non-enzyme-dependent effects that change gut microbiota composition and bioactive microbial aromatic amino acid metabolite levels, which is also influenced by aging. Certain gut microbiota species and metabolites may serve as prognostic markers for predicting outcomes to immunotherapy for GBM. These findings warrant further investigation into how IDO1 interacts with age to affect immunotherapeutic efficacy in subjects with GBM. Citation Format: Lijie Zhai, Akriti Shrestha, Kristen L. Lauing, Manon Penco-Campillo, Oluwatomilayo Odum, Prashant Bommi, Taylor Koch, Robert H. McCusker, Douglas E. Anderson, Anand Germanwala, Vikram C. Prabhu, Jigisha P. Thakkar, Jacob M. Allen, Rimas V. Lukas, Derek A. Wainwright. Age and indoleamine 2,3-dioxygenase 1 (IDO1) interact to affect gut microbiome homeostasis in subjects with glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2215.

Probiotic Lactobacillus rhamnosus GG Alleviates Prehypertension and Restores Gut Health and Microbiota in NaCl-Induced Prehypertensive Rats.

Probiotics could be used as adjuvant treatments in prehypertension management to restore gut microbiota dysbiosis caused by a high-salt diet. This study investigated the antihypertensive effects of the probiotic Lactobacillus rhamnosus strain GG (LGG) on high-salt diet-induced prehypertensive rats. Eighteen Sprague-Dawley rats were assigned equally into three groups: normotensive fed on a normal diet (ND), prehypertensive induced on a 4% NaCl high-salt diet (HSD), and prehypertensive induced on an HSD treated with LGG at 1 × 109 CFU daily for 8weeks (LGG). Weekly changes in water, food, body weight, diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) were monitored. Serum levels of Na, K, Cl, ALB, Ca, and TP were measured at the end of treatment, along with morphological and histomorphometric changes in the small intestine. Stool samples collected before (W0) and 8weeks after treatment (W8) were sequenced for bacterial 16S rDNA metagenomics. Probiotic LGG significantly reduces average DBP, SBP, and MAP while improving gut integrity through intact intestine morphology, higher villus heights, and a V/C ratio. At the genus level, the LGG group's gut microbiota composition is more similar to the HSD profile at W0 but shifts to the ND profile after treatment at W8. Thus, probiotic LGG lowers blood pressure indices, improves serum biochemistry profile, restores small intestinal integrity barrier, and modulates gut microbiota profile, indicating its potential as an adjuvant treatment for prehypertension and the significance of gut health in blood pressure regulation.

Relationships among osteoporosis, redox homeostasis, and alcohol addiction: Importance of the brain-bone axis.

Relationships among osteoporosis, redox homeostasis, and alcohol addiction: Importance of the brain-bone axis.

Oral exposure to nanoplastics and food allergy in mice fed a normal or high-fat diet.

Oral exposure to nanoplastics and food allergy in mice fed a normal or high-fat diet.

Intervention effects of greenspace exposure on human microbiota: A randomized controlled trial in Chinese young adults.

Intervention effects of greenspace exposure on human microbiota: A randomized controlled trial in Chinese young adults.

β-Glucan Extracted from Pichia kudriavzevii DPUL-51-6Y, Kluyveromyces marxianus DPUL-F15, and Saccharomyces cerevisiae DPUL-C6 Shows Ameliorating Effects on DSS-Induced Ulcerative Colitis on BALB/c Mice.

β-Glucans derived from yeast are recognized as beneficial food additives. This study evaluated crude β-glucan extracts from Pichia kudriavzevii DPUL-51-6Y, Kluyveromyces marxianus DPUL-F15, and Saccharomyces cerevisiae DPUL-C6 strains for their anticolitis potential. Chemical analysis revealed that β-glucan was the primary component (71.88-78.47% purity). Notably, the S. cerevisiae extract displayed superior thermal stability and hydration capacity. In RAW264.7 macrophages, β-glucan pretreatment at 100 μg/mL significantly reduced LPS-induced nitric oxide production and pro-inflammatory cytokines by suppressing NF-κB signaling through the reduction of p65 and IκB-α while simultaneously activating the Nrf2 and AHR pathways. In DSS-induced colitis BALB/c mice, oral administration of crude β-glucans alleviated intestinal damage by enhancing tight junction protein expression and restoring gut microbiota composition, characterized by an increased abundance of Lactobacillus and Prevotella. These effects were correlated with the increased production of microbial metabolites, including indole-3-lactic acid, indole-3-β-acrylic acid, tryptophol, and short-chain fatty acids (acetic, propionic, and butyric acids). Mechanistically, β-glucan mitigated colitis through the dual activation of Nrf2/AHR pathways and the inhibition of NF-κB. This study suggests that yeast-derived β-glucan plays a significant role in mitigating the inflammatory response and may alleviate ulcerative colitis by reshaping the microbial community and metabolite profiles in the host intestinal tract.

Effects of Dietary Fiber and Acetate on Alcoholic Heart Disease and Intestinal Microbes in Mice.

Alcoholic heart disease (AHD) is a severe cardiovascular condition linked to chronic alcohol consumption. This study investigates the effects of a high-fiber diet and acetate on gut microbiota and cardiac function in AHD mouse models. Sixty male C57BL/6 mice were divided into six groups, receiving either a control diet, high-fiber diet, or acetate supplementation alongside alcohol treatment. Results revealed that cardiac fibrosis and heart failure were notably improved in the AHD mice receiving high-fiber or acetate diets. Transcriptomic analyses indicated that dietary interventions modulated the expression of genes involved in lipid metabolism and the TGF-β signaling pathway. Additionally, 16S rRNA sequencing showed that the high-fiber diet and acetate altered gut microbiota composition, enhancing the abundance of beneficial bacteria such as Akkermansia muciniphila, Lactobacillus intestinalis, and Bacteroides acidifaciens. These microbes exhibited positive correlations with genes related to fat metabolism and TGF-β signaling, suggesting a potential mechanism for gut microbiota's role in AHD pathology. ROC analysis identified these bacteria as promising biomarkers for AHD detection. Overall, our findings underscore the therapeutic potential of dietary fiber and acetate in modulating gut microbiota and improving cardiac function in AHD, highlighting the intricate relationship between gut health and cardiovascular disease management.

Dietary drivers of gut microbiota diversity and function in wildlife of wolong nature reserve: a metagenomic study

Abstract While diet is known to regulate the composition, function, and diversity of the human gut microbiome, its effects on wildlife remain understudied. Here, non-invasive sampling methods were first used to conduct metagenomic analyses of gut microbiomes of 10 protected wild animals in the Wolong Nature Reserve. There were significant differences in microbiota composition and function between herbivores and carnivores. Herbivores exhibited higher microbial diversity and evenness (Shannon and Pielou indices), with Bacillota and Acinetobacter predominating, whereas carnivores were enriched in Pseudomonadota and Escherichia. Cellulose-degrading bacterium Ruminococcus champanellensis was abundant in herbivores, while Rhodococcus and Pediococcus, which were associated with toxin degradation and pathogen inhibition, were more prevalent in carnivores. Carnivores showed higher lipid metabolism and protein degradation, as evidenced by the enrichment of leucyl aminopeptidase and oligopeptidase B, while herbivores demonstrated superior cellulose and starch digestion, characterized by the enrichment of cellulose 1,4-beta-cellobiosidase. Stochastic processes shaped gut microbiome assembly, especially in herbivores. Potential health risks from pathogens such as Escherichia and Listeria were identified, and Escherichia abundance was positively correlated with niche width. Furthermore, the findings suggest that high-altitude environments may promote the persistence and spread of pathogens. Overall, our findings underscore the intricate linkages between diet, gut microbiota composition, assembly processes, and host ecology in protected wildlife, address a key knowledge gap, and provide important theoretical and practical insights for ecological conservation, species restoration, and environmental management.

Bacillus Coagulans BC99 Protects Ionizing Radiation-Induced Intestinal Injury and Modulates Gut Microbiota and Metabolites in Mice.

The gastrointestinal tract is highly sensitive to ionizing radiation (IR), which causes radiation-induced intestinal injury (RIII). There are no effective drugs available for RIII in routine clinical treatment, which is a major limiting factor during the process of radiotherapy for pelvic abdominal malignancies. In this study, we aimed to elucidate the potential of probiotic Bacillus coagulans BC99 (B.coagulans BC99) in preventing RIII. C57BL/6J mice were gavage-administered with B.coagulans BC99 for 30 days and then exposed to a single dose of 12Gy x-ray whole abdominal irradiation (WAI). B.coagulans BC99 treatment could mitigate RIII by preventing weight loss, maintaining the integrity of intestinal structure and barrier, improving inflammatory symptoms, modulating oxidative stress, and regulating the composition of gut microbiota, thereby reestablishing intestinal homeostasis. In addition, the potential radioprotective mechanism of B.coagulans BC99 was closely related to the gut microbiota-derived metabolites. This study offers a novel perspective for advancing probiotic-based treatments for RIII and enhancing strategies for the prevention of RIII.

Restricted versus ad libitum Feeding during Sow Gestation Affects Piglet Performance, Behavior, and Fecal Microbiota Composition.

This study investigated how the nutrition of gestating sows affects piglet performance, behavior, and fecal microbiota. Twenty-four sows were divided into two feeding groups: those on a restricted diet (once a day) and those fed ad libitum (as much as they wanted), with all receiving the same diet during lactation. The piglets were categorized based on their feeding groups; RG-RL: Piglets born and nursed by restricted-fed sows with restricted feeding, AG-AL: Piglets born and nursed by ad lib-fed sows, RG-AL: Piglets born by restricted-fed sows and nursed by ad lib-fed sows, and AG-RL: Piglets born by ad lib-fed sows and nursed by restricted-fed sows. Performance traits were analyzed using the model including treatment, switching piglets, and room effects. Piglet behavior was evaluated with a generalized linear mixed model (GLMM) using binomial distribution, testing interactions of treatment, switching, gender, and other factors while accounting for random effects related to room, pen, and sow. Results showed that ad lib-fed sows had higher feed intake (P < 0.001), weight gain (P = 0.04), and backfat gain (P = 0.01) compared to restricted-fed sows. They also had lower cortisol levels during gestation (P = 0.02) and lactation (P = 0.04). Restricted-fed sows displayed more air-chewing behavior (P = 0.002), while ad lib-fed sows were more active (P = 0.03) and engaged in eating (P < 0.001). Birth weights and the number of piglets were similar across groups. During lactation, backfat loss varied among piglet groups, with the highest loss in AG-RL (P < 0.01). Piglets from ad lib-fed sows performed better overall, regardless of nursing source. At weaning, piglet weights (P = 0.01) were highest in AG-AL, followed by RG-AL, RG-RL, and AG-RL (interaction effect P = 0.006). Switching piglets initially reduced their playtime but later increased it (P = 0.04). The novel object test indicated that gilts became more active, resembling boars. Additionally, gut microbiota composition varied among sow groups during gestation (P = 0.04) and lactation (P = 0.02), suggesting that maternal diet influences piglet gut health. Overall, these findings highlight the potential role of epigenetic mechanisms in shaping these traits.

Green Tea Ameliorates Depression-Like Behavior and Cognitive Impairment Induced by High-Fat Diet and Chronic Mild Stress.

Depression often develops in young individuals and is linked to complications like cognitive impairment. Conventional antidepressants show limited efficacy in restoring cognitive function and may cause adverse effects. Green tea, a safe and health-promoting beverage, offers various health benefits. This study investigated the effects of long-term green tea consumption on stress-induced depression-like behavior and mild cognitive impairment in animal models. We established a rodent model of mild depression and studied the effects of green tea on depression-like behavior and cognitive impairment through comprehensive evaluation, including behavioral assessments, neurotransmitter quantification, gene and protein expression analysis, blood metabolite profiling, and gut microbiota characterization. Results demonstrated significant improvements in mood, long-term memory, and sterol and glycerophospholipid metabolism. Green tea repaired the intestinal barrier and upregulated genes vital for tight junctions and mucin production. It also enhanced gut microbiota composition, reducing the Firmicutes-to-Bacteroidetes ratio and promoting beneficial bacteria such as NK4A136, Muribaculum, and Gordonibacter. These microbiota changes improved liver lipid metabolism and alleviated depressive symptoms. Green tea effectively mitigates depression-like behavior and cognitive deficits by modulating the gut-liver-brain axis.

Synergistic activity of synbiotic blend between Lactococcus lactis KAFF 1-4 and fibersol-2 on gut microbiota modulation and anti-VRE properties.

The study evaluated the effectiveness of a synbiotic blend containing Lactococcus lactis KA-FF 1-4 and Fibersol-2 in modulating gut microbiota and inhibiting vancomycin-resistant Enterococcus (VRE). Compared to probiotic or prebiotic treatments alone, the synbiotic blend significantly altered the gut microbiota composition, increasing beneficial bacteria like Blautia, Clostridium, Parabacteroides, Prevotella, and Roseburia, while reducing VRE abundance. Moreover, the synbiotic treatment showed an increase in short-chain fatty acid (SCFA) concentrations, particularly acetate, propionate, and butyrate. Correlation analysis revealed that enriched taxa in the synbiotic treatment were positively associated with higher SCFA levels. These findings highlight the potential of synbiotic formulations in improving gut microbiota balance and combating antibiotic-resistant pathogens like VRE.

Effects of chronic allergic lung inflammation on gut microbiota and depression-like behavior in mice

Aim: Emerging epidemiological studies have reported a link between allergic diseases, including asthma, and depression. Evidently, the gut microbiota is involved in the pathogenesis of asthma and depression. Therefore, we investigated whether allergic lung inflammation in mice causes gut microbial dysbiosis, via the gut-brain axis, which is potentially associated with depression. Methods: Wild-type C57BL/6J female mice were sensitized with intranasal house dust mite (HDM) antigen or phosphate-buffered saline (PBS) for 6 weeks to induce chronic allergic lung inflammation. Sucrose preference tests were performed for assessing depression. Fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between the HDM and PBS groups. The distance calculation, clustering of operational taxonomic units, rarefaction analysis, and estimator calculation (α- and β-diversity) were performed. Results: There was a significant difference in β-diversity (Bray-Curtis dissimilarity, F-statistics = 6.16, p = 0.001) of the gut microbiota between HDM and PBS groups. However, there was no difference in the α-diversity. We observed multiple differentially abundant bacteria in the HDM and PBS groups. The order class Clostridia (p = 0.0036) and genus Faecalibaculum (p = 0.028) were more abundant in the HDM group, whereas the phylum Firmicutes (p = 0.037) and genera Dubosiella (p = 0.00024) and Turicibacter (p = 0.037) were more abundant in the PBS group. Notably, the relative abundance of some bacteria was correlated with the sucrose preference test results. Conclusions: Six weeks of intranasal HDM administration to mimic the chronic status of lung inflammation in asthma changed the gut microbiome in mice and was associated with depression-like behavioral changes.

Modulation of the gut-bone axis: Lacticaseibacillus paracasei LC86 improves bone health via anti-inflammatory metabolic pathways in zebrafish models of osteoporosis and cartilage damage

AimOsteoporosis and cartilage injury are major health concerns with limited treatment options. This study investigates the therapeutic effects of Lacticaseibacillus paracasei LC86 (LC86) on osteoporosis and cartilage damage in a zebrafish (Danio rerio) model, focusing on its modulation of the gut-bone axis and its potential mechanisms for enhancing bone health.MethodsA Dexamethasone-induced zebrafish model was used to mimic osteoporosis and cartilage injury. Zebrafish were divided into control, model, and LC86 treatment groups (3×107 CFU/mL). Bone and cartilage health were assessed using Alizarin red staining and fluorescence microscopy. Bone marker expression (sp7, runx2a, bmp2a, bmp4, and col2a1a) was quantified via qPCR. Metabolic alterations were analyzed using untargeted metabolomics, and changes in gut microbiota were examined through 16S rRNA gene sequencing.ResultsLC86 treatment significantly improved bone and cartilage health, as evidenced by increased fluorescence intensity in the skull, hard bone, and cartilage (p &amp;lt; 0.01, p &amp;lt; 0.05). qPCR results showed upregulation of key bone-related genes (sp7, runx2a, bmp2a, bmp4, and col2a1a), indicating enhanced bone and cartilage structure. Metabolomics analysis revealed alterations in over 300 metabolites, with changes in anti-inflammatory and energy pathways. Gut microbiota analysis demonstrated an increase in beneficial bacteria and a decrease in pathogenic genera.ConclusionsLC86 significantly improved bone health, cartilage structure, and gut microbiota composition in a Dexamethasone-induced zebrafish model, supporting its potential as a therapeutic strategy for osteoporosis and cartilage injury via modulation of the gut-bone axis.

Influence of gut microbiota and immune markers in different stages of colorectal adenomas

ObjectiveColorectal adenomas (CRA) are the primary precancerous lesions leading to colorectal cancer (CRC). Early detection and intervention of CRA can significantly reduce the incidence of CRC. We investigated the relationships between the gut microbiome and the expression levels of PD-L1, IL-6, and IFN-γ at different CRA stages.MethodsParticipants were divided into normal, non-advanced adenoma (NAA), and advanced adenoma (AA) groups. PD-L1 expression in collected tissues was analyzed via immunohistochemistry (IHC) and Western blotting. Serum IL-6 and IFN-γ levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). 16S rRNA gene sequencing was used to examine gut microbiota changes, with correlation analysis to assess microbial influences on CRA progression.ResultsThe main differences in bacterial composition among the three groups were found within the Firmicutes and Bacteroidetes phyla. In the normal vs. NAA comparison, Clostridium sensu stricto, Faecalimonas, Gemmiger, and Ruminococcus were more abundant in the normal group, while Solobacterium was enriched in the NAA group. For the normal vs. AA comparison, the normal group was enriched with Anaerostipes, Blautia, Clostridium sensu stricto, Intestinibacter, Phocaeicola, and Turicibacter, whereas Solobacterium was more abundant in the AA group. In the NAA vs. AA comparison, the NAA group exhibited higher levels of Blautia, Faecalimonas, and Turicibacter relative to the AA group. Anaerostipes and Blautia are positively correlated with taurine and hypotaurine metabolism, propanoate metabolism, and zeatin biosynthesis. PD-L1 protein levels progressively increase with CRA advancement. Additionally, Faecalimonas, and Solobacterium were negatively associated with IFN-γ, while Gemmiger, and Anaerostipes were positively associated with IL-6.ConclusionThis study highlights the dynamic alterations in gut microbiota composition and their potential influence on the regulation of inflammatory cytokines and PD-L1 expression during CRA progression. The enrichment of protective taxa, such as Anaerostipes and Blautia, in the normal group emphasizes their potential role in mitigating adenoma progression. Dietary modulation to promote the proliferation of these beneficial bacteria could serve as a promising strategy to improve colorectal health. Future research should further explore the specific relationships between dietary components, gut microbiota, and metabolic pathways, and assess the effects of dietary interventions on gut health.

Irisin mitigates osteoporotic-associated bone loss and gut dysbiosis in ovariectomized mice by modulating microbiota, metabolites, and intestinal barrier integrity

BackgroundOsteoporotic bone defects significantly affect patient health and quality of life. The gut-bone axis plays a crucial role in osteoporosis, and disruptions in gut microbiota are linked to systemic inflammation and compromised bone metabolism. Irisin, a myokine, has shown potential in protecting against osteoporosis, but its mechanisms of action on the gut-bone axis remain unclear. This study aimed to investigate the role of irisin in mitigating osteoporotic bone defects by examining its effects on gut microbiota, related metabolites, and intestinal barrier integrity.MethodsAn osteoporosis model was created using ovariectomized (OVX) mice. The mice were divided into Sham, OVX, and r-irisin groups. Mice in the r-irisin group received intraperitoneal injections of 100 μg/kg irisin twice weekly for five weeks. Bone parameters were analyzed by micro-CT and histological staining. Gut microbiota composition was examined via 16S rDNA sequencing. Intestinal cytokines and barrier proteins were measured using immunohistochemistry and ELISA. Fecal metabolomic profiling was conducted using liquid chromatography-tandem mass spectrometry (LC–MS/MS), and correlations between gut microbiota, metabolites, and bone metabolism markers were evaluated.ResultsIrisin treatment improved bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular bone thickness (Tb.Th), and trabecular number (Tb.N), and reduced trabecular separation (Tb.Sp) in OVX mice. It enhanced new bone formation and collagen deposition. Irisin restored intestinal barrier integrity by increasing tight junction protein expression and reducing inflammatory cytokines in intestinal tissues. It also modulated gut microbiota diversity, reducing Firmicutes and increasing Verrucomicrobiota abundance. Key fecal metabolites, including atractylon (r = − 0.60, P < 0.01) and enterodiol (r = + 0.83, P < 0.01), showed strong correlations with BMD.ConclusionIrisin mitigates osteoporotic bone defects by enhancing bone formation, restoring intestinal barrier integrity, modulating gut microbiota composition, and influencing fecal metabolites. These preclinical findings highlight irisin’s potential to mitigate osteoporosis via the gut-bone axis.

Potential Beneficial Effects of Ocimum gratissimum on Male Fertility: Implication of the Gut-Testicular Axis

This review explores the potential of Ocimum gratissimum, a widely used medicinal plant, to positively influence male fertility, with a particular focus on the emerging role of the gut-testicular axis. Male infertility is a significant global health concern, often linked to oxidative stress, inflammation, and hormonal imbalances. Ocimum gratissimum possesses known antioxidant, anti-inflammatory, and antimicrobial properties, suggesting a potential therapeutic role. This review conducted a search using databases such as PubMed, Scopus, and Web of Science, focusing on studies investigating the effects of Ocimum gratissimum on male reproductive parameters, gut microbiota composition, and related biochemical pathways. Search terms included "Ocimum gratissimum," "male fertility," "sperm quality," "testosterone," "gut microbiota," "gut-testicular axis," and related terms. Studies were evaluated for relevance, rigor, and data quality. Available evidence suggests that Ocimum gratissimum may improve sperm quality, increase testosterone levels, and reduce oxidative stress in animal models. Furthermore, its antimicrobial properties could potentially modulate gut microbiota composition, influencing the production of metabolites that impact testicular function and hormone regulation via the gut-testicular axis. However, the exact mechanisms and specific bioactive compounds responsible for these effects remain to be fully elucidated, and human clinical trials are limited. In conclusion, Ocimum gratissimum holds promise as a potential natural agent for improving male fertility. Further research, particularly well-designed human studies, is warranted to validate these findings and to fully understand the role of the gut-testicular axis in mediating its effects. This could lead to the development of novel therapeutic strategies for male infertility.

Exposure to high altitude leads to disturbances in host metabolic homeostasis: study of the effects of hypoxia-reoxygenation and the associations between the microbiome and metabolome.

This study investigated alterations in hematological parameters, gut microbiota composition, and fecal and plasma metabolic profiles among high-altitude residents during reoxygenation periods of 1 week, 1 month, and 4 months to elucidate the effects of reoxygenation on human physiology and metabolism. Exposure to high altitudes alters intestinal flora, plasma and fecal metabolites, disrupting their metabolic balance. Distinct differences in amino acid, lipid, energy, immune, cofactor, and vitamin metabolism pathways were detected between high- and low-altitude populations, with a partial recovery of disparities during reoxygenation. Although the gut microbiota exhibited limited adaptive homeostasis to altitude variations, the abundance of microbial taxa and the expression levels of fecal metabolites during the initial reoxygenation phase, particularly during the first week, were sensitive to the reoxygenated environment. Through 16S rRNA gene sequencing and bioinformatics analysis, operational taxonomic units (OTUs) were annotated at the genus level, revealing that the genera Barnesiella, Parabacteroides, and Megasphaera, along with plasma L-arginine, S1P, and alpha-D-glucose, emerged as potential biomarkers for the first week of reoxygenation among high-altitude populations. Notably, a marked change in oxidative stress levels and an increase in antioxidant capacity were observed in high-altitude residents during early reoxygenation. Tyrosine metabolism, which is jointly regulated by the plasma and fecal metabolites and gut microbiota, plays an important role under high-altitude conditions during initial reoxygenation. Additionally, the plasma metabolites pyridoxine and hypoxanthine and the Rothia genus correlated significantly with high-altitude deacclimatization syndrome scores during the first week of reoxygenation.IMPORTANCEOur research focuses on the prompt activation of tyrosine metabolism in plasma following reoxygenation, along with the regulatory mechanisms employed by the intestinal microbiota and the metabolism of feces to modulate this metabolic process. Notably, in the initial stages of reoxygenation, specific microbial genera such as Barnesiella, Parabacteroides, and Megasphaera, alongside plasma biomarkers including L-arginine, S1P, and alpha-D-glucose, emerge as pivotal players. Additionally, our findings reveal a distinct hematological profile characterized by a decrease in the MCHC and increases in the MCV and RDW-SD during the first week of reoxygenation, and this temporal window marked a crucial juncture in the plasma metabolome. Whereas the first month of reoxygenation signified a pivotal phase in the gut microbiome's adaptation to altered environmental conditions, as evidenced by alterations in alpha diversity.

Effect of 1-Kestose on Lipid Metabolism in a High-Fat-Diet Rat Model

Objectives: Hyperlipidemia is a risk factor for various diseases. Identifying food components that can help reduce the levels of blood lipids, such as cholesterol and triglycerides, is a global research priority. It has been reported that 1-Kestose, a fructooligosaccharide, can reduce blood cholesterol and triglyceride levels in rats; however, the underlying mechanisms remain unclear. Therefore, we aimed to elucidate the effects of 1-kestose supplementation on lipid metabolism and the gut environment in rats. Methods: Twenty male Sprague–Dawley rats (age 8 weeks) were provided 1-kestose-containing water and were maintained for two weeks. After dissection, the blood components, hepatic gene expression, gut microbiota, and bile acid composition in the cecal contents of the rats were analyzed. Results: The 1-Kestose intake reduced plasma cholesterol and triglyceride levels. Additionally, an increase in cytochrome P450 family 7 subfamily A member 1 mRNA expression, a key gene for bile acid synthesis in the liver, and a decrease in lipid synthesis-related mRNA expression were observed. In the cecum, the levels of deconjugated bile acids, which are involved in the regulation of lipid synthesis, were increased. Furthermore, the 1-kestose intake altered the gut microbiota in the cecum, leading to an increase in the abundance of specific bacteria, such as Bifidobacterium, which are involved in the deconjugation of conjugated bile acids. Conclusions: The intake of 1-kestose alters the gut microbiota and bile acid metabolism in the cecum, potentially influencing lipid metabolism in the host.