Candida albicans overgrowth disrupts the gut microbiota in mice bearing oral cancer.

Candida albicans is one of the most common opportunistic fungi in cancer patients. This study explored the influence of C. albicans on gut microbiota in oral tumour-bearing mice by means of 16S rRNA sequencing and ITS sequencing. It was found that C. albicans infection induced the decrease of alpha diversity of bacteria and fungi in the gut microbiome. For the bacteria, C. albicans caused the reduction of Ralstonia, Alistipes, Clostridia UCG-014, Ruminococcus, and Lachnospiraceae NK4A136 group. For the fungi, C. albicans inhibited the growth of other fungi including Aspergillus, Cladosporium, and Bipolaris. The neutralisation of γδT cells partly alleviated the out-of-balance of Firmicutes/Bacteroidota (F/B) ratio in the gut caused by C. albicans infection. However, γδT cell neutralisation boosted the overgrowth of C. albicans. Additionally, IL-17A neutralisation aggravated the microbial dysbiosis of bacteria and fungi caused by C. albicans infection. Further analysis indicated that C. albicans overgrowth might influence the correlations between fungal and bacterial kingdoms. In conclusion, C. albicans infection disturbed the gut microbiota of both bacteria and fungi in oral tumour-bearing mice, which may be associated with the intestinal immune components including γδT cells and IL-17A.

The causal relationship between gut microbiota and biliary tract cancer: comprehensive bidirectional Mendelian randomization analysis.

Background: Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore the causal relationship between gut microbiota and BTC, conduct an appraisal of the gut microbiome's utility in facilitating the early diagnosis of BTC. Methods: We acquired the summary data for Genome-wide Association Studies (GWAS) pertaining to BTC (418 cases and 159,201 controls) from the Biobank Japan (BBJ) database. Additionally, the GWAS summary data relevant to gut microbiota (N = 18,340) were sourced from the MiBioGen consortium. The primary methodology employed for the analysis consisted of Inverse Variance Weighting (IVW). Evaluations for sensitivity were carried out through the utilization of multiple statistical techniques, encompassing Cochrane's Q test, the MR-Egger intercept evaluation, the global test of MR-PRESSO, and a leave-one-out methodological analysis. Ultimately, a reverse Mendelian Randomization analysis was conducted to assess the potential for reciprocal causality. Results: The outcomes derived from IVW substantiated that the presence of Family Streptococcaceae (OR = 0.44, P = 0.034), Family Veillonellaceae (OR = 0.46, P = 0.018), and Genus Dorea (OR = 0.29, P = 0.041) exerted a protective influence against BTC. Conversely, Class Lentisphaeria (OR = 2.21, P = 0.017), Genus Lachnospiraceae FCS020 Group (OR = 2.30, P = 0.013), and Order Victivallales (OR = 2.21, P = 0.017) were associated with an adverse impact. To assess any reverse causal effect, we used BTC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between BTC and five different types of gut microbiota. The sensitivity analysis disclosed an absence of empirical indicators for either heterogeneity or pleiotropy. Conclusion: This investigation represents the inaugural identification of indicative data supporting either beneficial or detrimental causal relationships between gut microbiota and the risk of BTC, as determined through the utilization of MR methodologies. These outcomes could hold significance for the formulation of individualized therapeutic strategies aimed at BTC prevention and survival enhancement.

Effects of Liqi Tongbian decoction on gut microbiota, SCFAs production, and 5-HT pathway in STC rats with Qi Stagnation Pattern.

Slow transit constipation (STC) is a common and debilitating condition characterized by delayed colonic transit and difficulty in fecal expulsion, significantly impacting patients' physical and mental wellbeing as well as their overall quality of life. This study investigates the therapeutic potential of Liqi Tongbian Decoction (LTD) in the treatment of STC, especially in cases involving the context of Qi stagnation, through a multifaceted approach involving the modulation of intestinal flora and short-chain fatty acids (SCFAs). We employed a rat model of STC with Qi Stagnation Pattern, established using the "loperamide + tail-clamping provocation method," to explore the effects of LTD on fecal characteristics, intestinal motility, and colonic pathology. Importantly, LTD exhibited the ability to increase the richness, diversity, and homogeneity of intestinal flora while also modulating the composition of microorganisms. It significantly increased the production of SCFAs, especially butyric acid. Moreover, LTD exerted a substantial influence on the synthesis of serotonin (5-HT) by modulating the expression of tryptophan hydroxylase (TPH) and interacting with the 5-HT4 receptor (5-HT4R), resulting in enhanced colonic motility. Correlation analyses revealed a positive correlation between certain bacterial genera, such as Lachnospiraceae_NK4A136 spp. and Clostridiales spp. and the concentrations of butyric acid and 5-HT. These results suggest a mechanistic link between microbiome composition, SCFAs production, and 5-HT synthesis. These findings highlight the potential of LTD to alleviate STC by facilitating a beneficial interplay among intestinal flora, SCFAs production, and 5-HT-mediated colonic motility, providing novel insights into the management of STC with Qi Stagnation Pattern.

Enterococcus durans 98D alters gut microbial composition and function to improve DSS-induced colitis in mice.

Enterococcus durans, is a potential functional strain with the capacity to regulate intestinal health and ameliorate colonic inflammation. However, the strain requires further investigation regarding its safety profile and potential mechanisms of colitis improvement. In this study, the safety of E. durans 98D (Ed) as a potential probiotic was studied using in vitro methods. Additionally, a dextran sulfate sodium (DSS)-induced murine colitis model was employed to investigate its impact on the intestinal microbiota and colitis. In vitro antimicrobial assays revealed Ed sensitivity to common antibiotics and its inhibitory effect on the growth of Escherichia coli O157, Streptococcus pneumoniae CCUG 37328, and Staphylococcus aureus ATCC 25923. To elucidate the functional properties of Ed, 24 weight-matched 6-week-old female C57BL/6J mice were randomly divided into three groups (n = 8): NC group, Con group (DSS), and Ed group (DSS + Ed). Ed administration demonstrated a protective effect on colitis mice, as evidenced by improvements in body weight, colonic length, reduced disease activity index, histological scores, diminished splenomegaly, and decreased goblet cell loss. Furthermore, Ed downregulated the expression of the pro-inflammatory cytokine genes (IL-6, IL-1ß, and TNF-α) and upregulated the expression of the anti-inflammatory cytokine gene IL-10. The 16S rRNA gene sequencing revealed significant alterations in microbial α-diversity, with principal coordinate analysis indicating distinct differences in microbial composition among the three groups. At the phylum level, the relative abundance of Actinomycetota significantly increased in the Ed-treated group. At the genus level, Ed treatment markedly elevated the relative abundance of Paraprevotella, Rikenellaceae_RC9, and Odoribacter in DSS-induced colitis mice. In conclusion, Ed exhibits potential as a safe and effective therapeutic agent for DSS-induced colitis by reshaping the colonic microbiota.

Comparative analysis of growth and health of juvenile African catfish (Clarias gariepinus) fed with different starch diets.

This study evaluated the effects of potato, wheat, rice, and corn starch on growth performance, blood parameters, digestive enzyme activity, antioxidative response, and gut microbiota of African catfish, Clarias gariepinus. A control diet (a commercial fish diet) and four different starch (potato, PO; wheat, WH; corn, CO; rice, RC) formulations were fed to African catfish with average weight of 10.5g (n = 30) for eight weeks. The experiment was conducted in triplicates. At the end of the feeding trial, the growth performance of African catfish fed with potato starch (PO) was significantly higher than other treatment groups. Furthermore, this group recorded significant and lowest feed conversion ratio (FCR) compared to other groups. Meanwhile, there were no significant differences in all tested hematological parameters and antioxidative response between the groups. Digestive enzyme activities in the fish intestines, including amylase, lipase, and protease, were significantly higher in African catfish fed with the PO diet. In addition, this group demonstrated substantially lower viscerosomatic index (VSI) and hepatosomatic index (HSI) than other groups, indicating that the fish has more meat on its body. The PO diet group also recorded significantly higher Akkermansia muciniphila, a good gut microbiota. Therefore, the PO diet potentially improves African catfish's growth performance and health status.

Similarities and differences: species and diet impact gut microbiota of captive pheasants.

The fecal microbiota plays an important role in maintaining animal health and is closely related to host life activities. In recent years, there have been an increasing number of studies on the fecal microbiota from birds. An exploration of the effects of species and living environments on the composition of gut microbiota will provide better protection for wildlife. In this study, non-injury sampling and 16S rDNA high-throughput sequencing were used to investigate the bacterial composition and diversity of the fecal microbiota in silver pheasants (Lophura nycthemera) and golden pheasants (Chrysolophus pictus) from Tianjin Zoo and Beijing Wildlife Park. The results showed that the abundance of Firmicutes was the highest in all fecal samples. At the genus level, Bacteroides was the common dominant bacteria, while there were some differences in other dominant bacteria genera. There were significant differences in fecal microbial composition between the golden pheasants from Tianjin Zoo and Beijing Wildlife Park. The metabolic analysis and functional prediction suggested that the gut microbiota composition and host metabolism were influenced by dietary interventions and living conditions. The results of this study provide the basis for further research of intestinal microbial of L. nycthemera and C. pictus, and valuable insights for conservation of related species.

Resveratrol and vascular health: evidence from clinical studies and mechanisms of actions related to its metabolites produced by gut microbiota.

Cardiovascular diseases are among the leading causes of mortality worldwide, with dietary factors being the main risk contributors. Diets rich in bioactive compounds, such as (poly)phenols, have been shown to potentially exert positive effects on vascular health. Among them, resveratrol has gained particular attention due to its potential antioxidant and anti-inflammatory action. Nevertheless, the results in humans are conflicting possibly due to interindividual different responses. The gut microbiota, a complex microbial community that inhabits the gastrointestinal tract, has been called out as potentially responsible for modulating the biological activities of phenolic metabolites in humans. The present review aims to summarize the main findings from clinical trials on the effects of resveratrol interventions on endothelial and vascular outcomes and review potential mechanisms interesting the role of gut microbiota on the metabolism of this molecule and its cardioprotective metabolites. The findings from randomized controlled trials show contrasting results on the effects of resveratrol supplementation and vascular biomarkers without dose-dependent effect. In particular, studies in which resveratrol was integrated using food sources, i.e., red wine, reported significant effects although the resveratrol content was, on average, much lower compared to tablet supplementation, while other studies with often extreme resveratrol supplementation resulted in null findings. The results from experimental studies suggest that resveratrol exerts cardioprotective effects through the modulation of various antioxidant, anti-inflammatory, and anti-hypertensive pathways, and microbiota composition. Recent studies on resveratrol-derived metabolites, such as piceatannol, have demonstrated its effects on biomarkers of vascular health. Moreover, resveratrol itself has been shown to improve the gut microbiota composition toward an anti-inflammatory profile. Considering the contrasting findings from clinical studies, future research exploring the bidirectional link between resveratrol metabolism and gut microbiota as well as the mediating effect of gut microbiota in resveratrol effect on cardiovascular health is warranted.

Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over the age of 50 years. Recent studies have suggested that the dysbiosis of the gut microbiota, a community of microorganisms in the human gut, is closely associated with the occurrence and development of CRC. Additionally, inflammatory factors (IFs) have also been reported to play a significant role in the development of CRC. However, the causal relationships between the gut microbiota, IFs, and CRC remain unclear. Methods: In this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to explore the causal relationship between the gut microbiota, IFs, and CRC. The gut microbiota GWAS data were obtained from the MiBioGen study, while the IFs GWAS data were derived from the comprehensive analysis of three independent cohorts. Causal relationship analysis was conducted using appropriate instrumental variables (IVs) and statistical models. Results: MR analysis of the gut microbiota and CRC revealed a negative correlation between the Lachnospiraceae species in the gut and CRC risk, while a positive correlation was observed between Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus in the gut, and CRC risk. Additionally, we observed a causal relationship between IL-10 and CRC risk. These findings suggest that the dysbiosis of the gut microbiota might be associated with an increased risk of CRC and that specific bacterial groups may play a crucial role in the occurrence and development of CRC. Conclusion: Using MR analysis, this study revealed the causal relationships between the gut microbiota, IFs, and CRC. The negative correlation between the Lachnospiraceae species in the gut and CRC risk, as well as the causal relationship between IL-10 and CRC, provide important clues for the potential roles of gut microbiota regulation and inflammatory factor control in the prevention and treatment of CRC.

Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research.

Background: Gut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases. Methods: Thirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates. Results: The combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10-3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10-3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10-2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10-2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10-3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity. Conclusion: This study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions.

Healthy Diets and Lifestyles in the World: Mediterranean and Blue Zone People Live Longer. Special Focus on Gut Microbiota and Some Food Components.

Longevity has been associated with healthy lifestyles, including some dietary regimens, such as the Mediterranean diet (MedDiet) and the Blue Zone (BZ) diets. MedDiet relies on a large consumption of fruit, vegetables, cereals, and extra-virgin olive oil, with less red meat and fat intake. Four major BZ have been recognized in the world, namely, Ogliastra in Sardinia (Italy), Ikaria (Greece), the Peninsula of Nicoya (Costa Rica), and Okinawa (Japan). Extreme longevity in these areas has been associated with correct lifestyles and dietary regimens. Fibers, polyphenols, beta-glucans, and unsaturated fatty acids represent the major constituents of both MedDiet and BZ diets, given their anti-inflammatory and antioxidant activities. Particularly, inhibition of the NF-kB pathway, with a reduced release of pro-inflammatory cytokines, and induction of T regulatory cells, with the production of the anti-inflammatory cytokine, interleukin- 10, are the main mechanisms that prevent or attenuate the "inflammaging." Notably, consistent physical activity, intense social interactions, and an optimistic attitude contribute to longevity in BZD areas. Commonalities and differences between MedDIet and BZ diets will be outlined, with special reference to microbiota and food components, which may contribute to longevity.

Dietary Supplementation with Nervonic Acid Ameliorates Cerebral Ischemia-Reperfusion Injury by Modulating of Gut Microbiota Composition-Fecal Metabolites Interaction.

SCOPE: Cerebral ischemia-reperfusion (IR) injury stands as a prominent global contributor to disability and mortality. Nervonic acid (NA), a bioactive elongated monounsaturated fatty acid, holds pivotal significance in human physiological well-being. This research aims to explore the prophylactic effects and fundamental mechanisms of NA in a rat model of cerebral IR injury. METHODS AND RESULTS: Through the induction of middle cerebral artery occlusion, this study establishes a rat model of cerebral IR injury and comprehensively assesses the pharmacodynamic impacts of NA pretreatment. This evaluation involves behavioral analyses, histopathological examinations, and quantification of serum markers. Detailed mechanisms of nervonic acid's prophylactic effects are revealed through fecal metabolomics and 16S rRNA sequencing analyses. Our findings robustly support nervonic acid's capacity to ameliorate neurological impairments in rats afflicted with cerebral IR injury. Beyond its neurological benefits, NA demonstrates its potential by rectifying metabolic perturbations across diverse pathways, particularly those pertinent to unsaturated fatty acid metabolism. Additionally, NA emerges as a modulator of gut microbiota composition, notably by selectively enhancing vital genera like Lactobacillus. CONCLUSION: These comprehensive findings highlight the potential of incorporating NA as a functional component in dietary interventions aimed at targeting cerebral IR injury.

Rosa laevigata Polysaccharides Ameliorate Dextran Sulfate Sodium-induced Ulcerative Colitis of Beagles through Regulating Gut Microbiota.

Rosa laevigata Michx. polysaccharides (RLP) have been demonstrated to possess antioxidant and anti-inflammatory properties. However, the mechanisms and efficacy of these polysaccharide components in preventing ulcerative colitis (UC) remain to be elucidated. The efficacy and mechanisms of RLP were investigated in a study that utilized healthy adult beagles to establish a UC model, considering the similarities in gut microbiota between humans and dogs. In the study, the beagle model induced by sodium dextran sulfate exhibited typical symptoms of ulcerative colitis, such as weight loss and diarrhea. All these symptoms and changes were significantly ameliorated through oral supplementation of RLP. Additionally, microbial community analysis based on the 16S rDNA gene revealed that RLP alleviated UC by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. In conclusion, our study has provided that RLP effectively alleviated colitis by preserving the intestinal barrier and regulating the gut microbiota composition.

Effects of host identity on the gut microbiota: A comparative study on three microtinae species.

BACKGROUND: Gut microbiota exert an immense effect on host health and host environmental adaptation. Furthermore, the composition and structure of gut microbiota are determined by the environment and host genetic factors. However, the relative contribution of the environment and host genetic factors toward shaping the structure of gut microbiota has been poorly understood. METHODS: In this study, we characterized the fecal microbial communities of the closely related voles Neodon fuscus, Lasiopodomys brandtii, and L. mandarinus after caged feeding in the laboratory for 6 months, through high-throughput sequencing and bioinformatics analysis. RESULTS: The results of pairwise comparisons of N. fuscus vs. L. brandtii and L. mandarinus vs. L. brandtii revealed significant differences in bacterial diversity and composition after domestication. While 991 same operational taxonomic units (OTUs) were shared in three voles, there were 362, 291, and 303 species-specific OTUs in N. fuscus, L. brandtii, and L. mandarinus, respectively. The relative abundances of Proteobacteria and Prevotella, which are reported to be enriched in high-altitude populations, were significantly higher in high-altitude N. fuscus than in low-altitude L. brandtii after domestication. Firmicutes, which produce various digestive enzymes for energy metabolism, and Spirochaetes, which can degrade cellulose, were found in higher abundance in subterranean L. mandarinus than that in L. brandtii which dwells on the earth surface. CONCLUSION: Our findings showed that some components of gut microbiota still maintained dominance even when different host species are reared under the same environmental conditions, suggesting that these bacteria are substantially influenced by host factors..

Disrupted gut microecology after high-dose 131I therapy and radioprotective effects of arachidonic acid supplementation.

BACKGROUND: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. METHODS: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. RESULTS: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.

Zamzam Water Mitigates Cardiac Toxicity Risk through Modulation of GUT Microbiota and the Renin-angiotensin System.

BACKGROUND: Cardiovascular diseases (CVDs) continue to exert a substantial global influence in specific areas due to population growth, aging, microbiota, and genetic/environmental factors. Drinking water has a strong impact on the health of an individual. Further, emerging evidence has highlighted the therapeutic potential and benefits of Zamzam water (Zam). OBJECTIVE: We investigated the influence of Zam on doxorubicin-induced cardiac toxicity, elucidating its consequential effects on GUT microbiota dysbiosis and hepatic and renal functions. METHODS: Male rats were categorized into four groups: Group 1 as Normal control (NC), Group 2 as Zamzam control (ZC), Group 3 Disease control (DC) and Group 4 as Therapeutic control (DZ) treated with Zam against doxorubicin-induced disease at a dose of 1mg/kg boy weight) intraperitoneally (i.p). RESULTS: Significant dysbiosis in the composition of GM was observed in the DC group along with a significant decrease (p < 0.05) in serum levels of Zinc, interleukin-10 (IL-10), IL-6 and Angiotensin II (Ang II), while C-reactive protein (CRP), fibrinogen, and CKMB increased significantly (restoration of Zinc ions (0.72 ± 0.07 mcg/mL) compared to NC. Treatment with Zamzam exhibited a marked abundance of 18-times to 72% in Romboutsia, a genus of firmicutes, along with lowering of Proteobacteria in DZ followed by significant restoration of Zinc ions (0.72 ± 0.07 mcg/mL), significant (p ˂ 0.05) reduction in CRP (7.22 ± 0.39 mg/dL), CKMB (118.8 ± 1.02 U/L) and Fibrinogen (3.18 ± 0.16 mg/dL), significant (p < 0.05) increase in IL-10 (7.22 ± 0.84 pg/mL) and IL-6 (7.18 ± 0.40 pg/ml), restoration of Ang II (18.62 ± 0.50 nmol/mL/min), marked increase in renin with normal myocyte architecture and tissue orientation of kidney, and restoration of histological architecture of hepatocyte. CONCLUSION: Zam treatment mitigated cardiac toxicity risk through the modulation of GUT microbiota and the renin-angiotensin system and tissue histology effectively.

Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short-Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD).

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short-chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. OBJECTIVES: To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. METHODS: Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography-mass spectrometry and 16S rRNA gene sequencing. RESULTS: Compared with NC, fecal SCFA levels (propionic, acetic, and butyric acid) were lower in iRBD, MSA, and PD. Combinations of these SCFAs could differentiate NC from iRBD (AUC 0.809), MSA (AUC 0.794), and PD (AUC 0.701). Decreased fecal SCFAs were associated with the common reducing SCFA-producing gut microbiota in iRBD, MSA, and PD. CONCLUSIONS: iRBD shares similar fecal SCFA alterations with MSA and PD, and the combination of these SCFAs might be a potential synucleinopathies-related biomarker. © 2024 International Parkinson and Movement Disorder Society.

Exploring the Role of Gut-Lung Interactions in COPD Pathogenesis: A Comprehensive Review on Microbiota Characteristics and Inflammation Modulation.

Chronic obstructive pulmonary disease (COPD) is a paramount contributor to global morbidity and mortality. Over the past decade, the concept of the "gut-lung axis" has emerged, offering a lens through which to examine the intricate interplay between the host, microbiome, and respiratory diseases, including COPD. An expanding body of evidence underscores that the composition of both the gastrointestinal and respiratory microbiome deviates in COPD patients compared to healthy individuals, leading to distinct host immune responses and clinical manifestations. The objective of this review is to provide a concise overview of the role of both gut and respiratory microbiome plays in the development of COPD. This will be accomplished by compiling current literature on the microbiome profile in stable and exacerbated cases of COPD, as well as exploring the biological mechanisms through a discussion of relevant experiments conducted on murine models. Hallmark characteristics of the microbial profile in COPD encompass reduced Prevotella spp. in the respiratory microbiome, culminating in a loss of anti-inflammatory protection, and diminished Bacteroidetes in the gut microbiome, leading to a decrease in protective short-chain fatty acids (SCFAs). The proliferation of Proteobacteria, particularly Haemophilus spp., Moraxella spp. and Pseudomonas spp. contributes to COPD pathologies via recognition of proinflammatory lipopolysaccharide (LPS) via Toll-like receptors (TLRs). As a consequence, deteriorated pulmonary function, enhanced severity, increased onset of exacerbations and elevated mortality were observed.

The interaction of inflammasomes and gut microbiota: novel therapeutic insights.

Inflammasomes are complex platforms for the cleavage and release of inactivated IL-1ß and IL-18 cytokines that trigger inflammatory responses against damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs). Gut microbiota plays a pivotal role in maintaining gut homeostasis. Inflammasome activation needs to be tightly regulated to limit aberrant activation and bystander damage to the host cells. Several types of inflammasomes, including Node-like receptor protein family (e.g., NLRP1, NLRP3, NLRP6, NLRP12, NLRC4), PYHIN family, and pyrin inflammasomes, interact with gut microbiota to maintain gut homeostasis. This review discusses the current understanding of how inflammasomes and microbiota interact, and how this interaction impacts human health. Additionally, we introduce novel biologics and antagonists, such as inhibitors of IL-1ß and inflammasomes, as therapeutic strategies for treating gastrointestinal disorders when inflammasomes are dysregulated or the composition of gut microbiota changes.

Natural mating ability is associated with gut microbiota composition and function in captive male giant pandas.

The issue of poor sexual performance of some male giant pandas seriously impairs the growth and the genetic diversity of the captive population, yet there is still no clear understanding of the cause of the loss of this ability and its underlying mechanism. In this study, we analyzed the gut microbiota and its function in 72 fecal samples obtained from 20 captive male giant pandas, with an equal allocation between individuals capable and incapable of natural mating. Additionally, we investigated fecal hormone levels and behavioral differences between the two groups. A correlation analysis was then conducted among these factors to explore the influencing factors of their natural mating ability. The results showed significant differences in the composition of gut microbiota between the two groups of male pandas. The capable group had significantly higher abundance of Clostridium sensu stricto 1 (p adjusted = .0021, GLMM), which was positively correlated with fatty acid degradation and two-component system functions (Spearman, p adjusted < .05). Additionally, the capable group showed higher gene abundance in gut microbiota function including purine and pyrimidine metabolism and galactose metabolism, as well as pathways related to biological processes such as ribosome and homologous recombination (DEseq2, p adjusted < .05). We found no significant differences in fecal cortisol and testosterone levels between the two groups, and no difference was found in their behavior either. Our study provides a theoretical and practical basis for further studying the behavioral degradation mechanisms of giant pandas and other endangered mammal species.

Symbiotic combination of Akkermansia muciniphila and inosine alleviates alcohol-induced liver injury by modulating gut dysbiosis and immune responses.

Background: Alcoholic liver disease (ALD) is exacerbated by disruptions in intestinal microecology and immune imbalances within the gut-liver axis. The present study assesses the therapeutic potential of combining Akkermansia muciniphila (A. muciniphila) with inosine in alleviating alcohol-induced liver injury. Methods: Male C57BL/6 mice, subjected to a Lieber-DeCarli diet with 5% alcohol for 4 weeks, served as the alcoholic liver injury model. Various analyzes, including quantitative reverse transcription polymerase chain reaction (qRT-PCR), ELISA, immunochemistry, 16S rRNA gene sequencing, and flow cytometry, were employed to evaluate liver injury parameters, intestinal barrier function, microbiota composition, and immune responses. Results: Compared to the model group, the A. muciniphila and inosine groups exhibited significantly decreased alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide (LPS) levels, reduced hepatic fat deposition and neutrophil infiltration, alleviated oxidative stress and inflammation, and increased expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1). These effects were further pronounced in the A. muciniphila and inosine combination group compared to individual treatments. While alcohol feeding induced intestinal dysbiosis and gut barrier disruption, the combined treatment reduced the abundance of harmful bacteria (Oscillibacter, Escherichia/Shigella, and Alistipes) induced by alcohol consumption, promoting the growth of butyrate-producing bacteria (Akkermansia, Lactobacillus, and Clostridium IV). Flow cytometry revealed that alcohol consumption reduced T regulatory (Treg) populations while increasing those of T-helper (Th) 1 and Th17, which were restored by A. muciniphila combined with inosine treatment. Moreover, A. muciniphila and inosine combination increased the expression levels of intestinal CD39, CD73, and adenosine A2A receptor (A2AR) along with enhanced proportions of CD4+CD39+Treg and CD4+CD73+Treg cells in the liver and spleen. The A2AR antagonist KW6002, blocked the beneficial effects of the A. muciniphila and inosine combination on liver injury in ALD mice. Conclusion: This study reveals that the combination of A. muciniphila and inosine holds promise for ameliorating ALD by enhancing the gut ecosystem, improving intestinal barrier function, upregulating A2AR, CD73, and CD39 expression, modulating Treg cells functionality, and regulating the imbalance of Treg/Th17/Th1 cells, and these beneficial effects are partly A2AR-dependent.