Interactions Between Oral Microbiota and Cancers in the Aging Community: A Narrative Review.

The oral microbiome potentially wields significant influence in the development of cancer. Within the human oral cavity, an impressive diversity of more than 700 bacterial species resides, making it the second most varied microbiome in the body. This finely balanced oral microbiome ecosystem is vital for sustaining oral health. However, disruptions in this equilibrium, often brought about by dietary habits and inadequate oral hygiene, can result in various oral ailments like periodontitis, cavities, gingivitis, and even oral cancer. There is compelling evidence that the oral microbiome is linked to several types of cancer, including oral, pancreatic, colorectal, lung, gastric, and head and neck cancers. This review discussed the critical connections between cancer and members of the human oral microbiota. Extensive searches were conducted across the Web of Science, Scopus, and PubMed databases to provide an up-to-date overview of our understanding of the oral microbiota's role in various human cancers. By understanding the possible microbial origins of carcinogenesis, healthcare professionals can diagnose neoplastic diseases earlier and design treatments accordingly.

Interactions between oral microbiota shifts and cancer: The oral microbiome potentially wields significant influence in the development of cancer. Within the human oral cavity, an impressive diversity of more than 700 bacterial species resides, making it the second most varied microbiome in the body. This finely balanced oral microbiome ecosystem is vital for sustaining oral health. However, disruptions in this equilibrium, often brought about by dietary habits and inadequate oral hygiene, can result in various oral ailments like periodontitis, cavities, gingivitis, and even oral cancer. There is compelling evidence that the oral microbiome is linked to several types of cancer, including oral, pancreatic, colorectal, lung, gastric, and head and neck cancers. This review discussed the critical connections between cancer and members of the human oral microbiota. Extensive searches were conducted across the Web of Science, Scopus, and PubMed databases to provide an up-to-date overview of our understanding of the oral microbiota's role in various human cancers. By understanding the possible microbial origins of carcinogenesis, healthcare professionals can diagnose neoplastic diseases earlier and design treatments accordingly.

Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.

Impact of Experimental Tuberculosis on Fertility of Female BALB/c Mice.

The study revealed no effects of pregnancy and childbirth on the course of tuberculosis in female BALB/c mice after aerosol infection with Mycobacterium tuberculosis. However, we demonstrated a negative effect of tuberculosis infection on the fertility of infected females, which manifested in a longer period from mating to pregnancy and in a smaller litter size. Impaired reproductive function in response to the effect of the systemic infectious process was accompanied by the development of immunosuppression confirmed by an immunological test (delayed-type hypersensitivity to tuberculin) and the formation of genital tract dysbiosis during pregnancy and postpartum period.

Biodegradation of four polyolefin plastics in superworms (Larvae of Zophobas atratus) and effects on the gut microbiome.

Recent studies have demonstrated superworms (larvae of Zophobas atratus) ability to degrade polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), and polypropylene (PP) within their digestive system. This study aimed to compare the ability of superworms to degrade the above four polyolefin plastics over a duration of 30 days. In this study, the degradation rate of PE was the highest, and the final average weight of superworms, as well as the final plastic mass loss consumed by them, significantly increased (73.38 % and 52.33 %, respectively) when PE was fed with wheat bran (1:1 [w/w]). FTIR and TGA indicated the occurrence of oxidation and biodegradation processes in the four polyolefin plastics when exposed to superworms. In addition, the molecular weights (Mw and Mn) of excreted polymer residues decreased by 3.1 % and 2.87 % in PE-fed superworms, suggesting that the depolymerization of PE was not entirely dependent on the gut microbial community. The analysis of the gut microbial communities revealed that the dominant microbial community were different for each type of plastic. The results indicate that the gut microbiome of superworms exhibited remarkable adaptability in degrading various types of plastics, and the intake preferences and efficiency of different plastics are associated with different dominant microbial community species.

Molecular mechanism and therapeutic strategy of bile acids in Alzheimer's disease from the emerging perspective of the microbiota-gut-brain axis.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-ß outside neurons and Tau protein inside neurons. Various pathological mechanisms are implicated in AD, including brain insulin resistance, neuroinflammation, and endocrinal dysregulation of adrenal corticosteroids. These factors collectively contribute to neuronal damage and destruction. Recently, bile acids (BAs), which are metabolites of cholesterol, have shown neuroprotective potential against AD by targeting the above pathological changes. BAs can enter the systematic circulation and cross the blood-brain barrier, subsequently exerting neuroprotective effects by targeting several endogenous receptors. Additionally, BAs interact with the microbiota-gut-brain (MGB) axis to improve immune and neuroendocrine function during AD episodes. Gut microbes impact BA signaling in the brain through their involvement in BA biotransformation. In this review, we summarize the role and molecular mechanisms of BAs in AD while considering the MGB axis and propose novel strategies for preventing the onset and progression of AD.

Enhanced Cerebral Blood Flow Similarity of the Somatomotor Network in Chronic Insomnia: Transcriptomic decoding, Gut Microbial Signatures and Phenotypic Roles.

Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4% variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7% inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4%). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.

Effects of Lactobacillus plantarum on Broiler Health: Integrated Microbial and Metabolomics Analysis.

Given China's prohibition on the utilization of antibiotics as feed additives in 2020, we aim to investigate nutrition additives that are both efficient and safe. Lactobacillus, a well-recognized beneficial probiotic, has explicitly been investigated for its effects on health status of the host and overall impact on food industry. To evaluate effects of Lactobacillus plantarum (LW) supplementation on broiler chicken, we conducted comprehensive multi-omics analysis, growth performance evaluation, RT-qPCR analysis, and immunofluorescence. The findings revealed that LW supplementation resulted in a substantial progress in growth performance (approximately 205 g increase in final body weight in comparison to the control group (p < 0.01)). Additionally, LW exhibited promising potential for enhancing antioxidant properties of serum and promoting gut integrity and growth as evidenced by improved antioxidant indices (p < 0.01), intestinal villus morphology (p < 0.01), and enhanced gut barrier function (p < 0.01). Meanwhile, the multi-omics analysis, including 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry, revealed an enrichment of beneficial microbes in the gut of broilers that were supplemented with LW, while simultaneously depleting harmful microorganisms. Moreover, a noteworthy modification was observed in gut metabolic profiling subsequent to the execution of the probiotic strategy. Specifically, variations were noticed in the levels of metabolites and metabolic pathways such as parathyroid hormone synthesis, inflammatory mediator regulation of TRP channels, oxidative phosphorylation, and mineral absorption. Taken together, our findings validate that LW administration produces valuable effects on the health and growth performance of broilers owing to its capability to boost the gut microbiota homeostasis and intestinal metabolism. Present findings signify the potential of LW as a dietary additive to promote growth and development in broiler chickens.

Exploring the causal connection: insights into diabetic nephropathy and gut microbiota from whole-genome sequencing databases.

Over recent years, the prevalence of diabetes has been on the rise, paralleling improvements in living standards. Diabetic nephropathy (DN), a prevalent complication of diabetes, has also exhibited a growing incidence. While some clinical studies and reviews have hinted at a link between diabetic nephropathy and gut microbiota (GM), the nature of this connection, specifically its causative nature, remains uncertain. Investigating the causal relationship between diabetic nephropathy and gut microbiota holds the promise of aiding in disease screening and identifying novel biomarkers. In this study, we employed a two-sample Mendelian randomization analysis. Our dataset encompassed 4,111 DN patients from the GWAS database, juxtaposed with 308,539 members forming a control group. The aim was to pinpoint specific categories within the vast spectrum of the 211 known gut microbiota types that may have a direct causal relationship with diabetic nephropathy. Rigorous measures, including extensive heterogeneity and sensitivity analyses, were implemented to mitigate the influence of confounding variables on our experimental outcomes. Ultimately, our comprehensive analysis revealed 15 distinct categories of gut microbiota that exhibit a causal association with diabetic nephropathy. In summary, the phyla Bacteroidota and Verrucomicrobiae, the families Peptostreptococcaceae and Veillonellaceae, the genus Akkermansia, and the species Catenibacterium, Lachnoclostridium, Parasutterella, along with the orders Bacteroidales and Verrucomicrobiales, and the class Bacteroidetes were identified as correlates of increased risk for DN. Conversely, the family Victivallaceae, the species Eubacterium coprostanoligenes, and the Clostridium sensu stricto 1 group were found to be associated with a protective effect against the development of DN.These findings not only provide valuable insights but also open up novel avenues for clinical research, offering fresh directions for potential treatments.

Personalized Microbial Fingerprint Associated with Differential Glycemic Effects of a Whole Grain Rye Intervention on Chinese Adults.

SCOPE: This study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an "enterotype - metabolic" model. METHODS AND RESULTS: A 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7ß-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis. CONCLUSION: The work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.

The effect of gut microbiome and plasma metabolome on systemic sclerosis: a bidirectional two-sample Mendelian randomization study.

Background: Cellular and molecular biology, combined with research on the human microbiome and metabolome, have provided new insights into the pathogenesis of systemic sclerosis (SSc). However, most studies on gut microbiota (GM) and metabolome in SSc are observational studies. The impact of confounding factors and reverse causation leads to different insights. To shed light on this matter, we utilized Mendelian randomization (MR) to determine the causal effect of GM/metabolites on SSc. Methods: Based on summary-level data from genome-wide association studies, bidirectional Two-sample MR was conducted involving 196 GM, 1400 plasma metabolism, and 9,095 SSc. Inverse Variance Weighting (IVW) was mainly used for effect estimation. Results: Forward MR analysis found that three GM and two plasma metabolites are causally related to SSc. IVW results showed Victivallaceae (family) (OR, 1.469; 95%CI, 1.099-1.963; p = 0.009) and LachnospiraceaeUCG004 (genus) (OR, 1.548; 95%CI, 1.020-2.349; p = 0.04) were risk factor of SSc. Conversely, Prevotella7 (genus) (OR, 0.759; 95%CI, 0.578-0.997; p = 0.048)was a protective factor of SSc. The results on plasma metabolites indicated that Pregnenediol disulfate (C21H34O8S2) levels (OR, 1.164; 95%CI, 1.006-1.347; p = 0.041)was a risk factor of SSc, while Sphingomyelin (d18:1/19:0, d19:1/18:0) levels (OR, 0.821; 95%CI, 0.677-0.996; p = 0.045)was a protective factor of SSc. Reverse MR analysis did not find causally relationship between SSc and the above GM/plasma metabolites. Conclusion: Our results revealed the causally effect between GM/plasma metabolites and SSc. These findings provided new insights into the mechanism of SSc. In particular, we demonstrated Prevotella7 was a protective factor of SSc despite its controversial role in SSc in previous researches.

Causal relationship between gut microbiota and constipation: a bidirectional Mendelian randomization study.

Background: Constipation is a prevalent gastrointestinal disorder affecting approximately 15% of the global population, leading to significant healthcare burdens. Emerging evidence suggests that gut microbiota plays a pivotal role in the pathogenesis of constipation, although causality remains uncertain due to potential confounding factors in observational studies. This study aims to clarify the causal relationships between gut microbiota and constipation using a bidirectional Mendelian Randomization (MR) approach, which helps to overcome confounding issues and reverse causality. Methods: Utilizing data from genome-wide association studies (GWAS) from the MiBioGen consortium and other sources, we identified genetic variants as instrumental variables (IVs) for 196 bacterial traits and constipation. These IVs were rigorously selected based on their association with the traits and absence of linkage with confounding factors. We applied several MR methods, including Inverse Variance Weighted (IVW), MR Egger, and MR-PRESSO, to examine the causal effects in both directions. Results: Our analysis revealed a significant causal relationship where specific bacterial taxa such as Coprococcus1 (OR = 0.798, 95%CI: 0.711-0.896, p < 0.001), Coprococcus3 (OR = 0.851, 95%CI: 0.740-0.979, p = 0.024), Desulfovibrio (OR = 0.902, 95%CI: 0.817-0.996, p = 0.041), Flavonifractor (OR = 0.823, 95%CI: 0.708-0.957, p < 0.001), and Lachnospiraceae UCG004, whereas others including Ruminococcaceae UCG005 (OR = 1.127, 95%CI: 1.008-1.261, p = 0.036), Eubacterium nodatum group (OR = 1.080, 95%CI: 1.018-1.145, p = 0.025), Butyricimonas (OR = 1.118, 95%CI: 1.014-1.233, p = 0.002), and Bacteroidetes (OR = 1.274, 95%CI: 1.014-1.233, p < 0.001) increase constipation risk. In the reverse MR analysis, constipation was found to influence the abundance of certain taxa, including Family XIII, Porphyromonadaceae, Proteobacteria, Lentisphaeria, Veillonellaceae, Victivallaceae, Catenibacterium, Sellimonas, and Victivallales, indicating a bidirectional relationship. Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or horizontal pleiotropy. Conclusion: The relationship between our study gut microbiota and constipation interacts at the genetic level, which gut microbiota can influence the onset of constipation, and constipation can alter the gut microbiota. Coprococcus1, Coprococcus3, Desulfovibrio, Flavonifractor and Lachnospiraceae UCG004 play a protective role against constipation, while Ruminococcaceae UCG005, Eubacterium nodatum group, Butyricimonas, and Bacteroidetes are associated with an increased risk. In addition, constipation correlates positively with the abundance of Family XIII, Porphyromonadaceae and Proteobacteria, while negatively with Lentisphaeria, Veillonellaceae, Victivallaceae, Catenibacterium, Sellimonas, and Victivallales.

The preventative effects of Lactococcus Lactis metabolites against LPS-induced sepsis.

Introduction: Sepsis is a syndrome of organ dysfunction caused by a dysregulated host response to infection and septic shock. Currently, antibiotic therapy is the standard treatment for sepsis, but it can lead to drug resistance. The disturbance of the gut microbiota which is affected by sepsis could lead to the development of organ failure. It is reported that probiotics could shape the gut microbiota, potentially controlling a variety of intestinal diseases and promoting whole-body health. Methods: In this study, we evaluated the preventive effects of intra- and extracellular products of probiotics on sepsis. The extracellular products of Lactococcus lactis (L. lactis) were identified through the in vivo cell experiments. The preventive effect and mechanism of L. lactis extracellular products on mouse sepsis were further explored through HE staining, mouse survival rate measurement, chip analysis, etc. Results: L. lactis extracellular products increase cell survival and significantly reduce inflammatory factors secreted in a cellular sepsis model. In in vivo experiments in mice, our samples attenuated sepsis-induced pulmonary edema and inflammatory infiltrates in the lungs of mice, and reduced mortality and inflammatory factor levels within the serum of mice. Finally, the mechanism of sepsis prevention by lactic acid bacteria is suggested. Extracellular products of L. lactis could effectively prevent sepsis episodes. Discussion: In animal experiments, we reported that extracellular products of L. lactis can effectively prevent sepsis, and preliminarily discussed the pathological mechanism, which provides more ideas for the prevention of sepsis. In the future, probiotics may be considered a new way to prevent sepsis.

More on the interplay between gut microbiota, autophagy, and inflammatory bowel disease is needed.

The concept of inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, represents a complex and growing global health concern resulting from a multifactorial etiology. Both dysfunctional autophagy and dysbiosis contribute to IBD, with their combined effects exacerbating the related inflammatory condition. As a result, the existing interconnection between gut microbiota, autophagy, and the host's immune system is a decisive factor in the occurrence of IBD. The factors that influence the gut microbiota and their impact are another important point in this regard. Based on this initial perspective, this manuscript briefly highlighted the intricate interplay between the gut microbiota, autophagy, and IBD pathogenesis. In addition, it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context. Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms, which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.

Genetically predicted elevated circulating 3,4-dihydroxybutyrate levels mediate the association between family Christensenellaceae and osteoporosis risk: a Mendelian randomization study.

Objective: To investigate the impact of gut microbiota on osteoporosis and identify the mediating role of blood metabolites in this process. Methods: This two-sample Mendelian randomization (MR) study utilized summary level data from genome-wide association studies (GWAS). Gut microbiota GWAS data were obtained from the MiBio-Gen consortium meta-analysis (n=13,266), while osteoporosis summary statistics were sourced from the FinnGen consortium R9 release data (7300 cases and 358,014 controls). Metabolite data, including 1400 metabolites or metabolite ratios, were derived from a study involving 8,299 unrelated individuals. The primary MR method employed was the inverse variance weighted (IVW) method. Reverse MR analysis was conducted on bacteria causally associated with osteoporosis in forward MR. The gut microbiota with the smallest p-value was selected as the top influencing factor for subsequent mediation analysis. A two-step MR approach quantified the proportion of the blood metabolite effect on gut microbiota influencing osteoporosis. IVW and Egger methods were used to assess heterogeneity and horizontal pleiotropy. Results: IVW estimates indicated a suggestive effect of family Christensenellaceae on osteoporosis (odds ratio(OR) = 1.292, 95% confidence interval(CI): 1.110-1.503, P =9.198 × 10-4). Reverse MR analysis revealed no significant causal effect of osteoporosis on family Christensenellaceae (OR = 0.947, 95% CI: 0.836-1.072, P =0.386). The proportion of the effect of family Christensenellaceae on osteoporosis mediated by circulating levels of 3,4-dihydroxybutyrate was 9.727%. No significant heterogeneity or horizontal pleiotropy was detected in the instrumental variables used for MR analysis. Conclusion: This study establishes a causal link between family Christensenellaceae and osteoporosis, with a minor proportion of the effect mediated by elevated circulating levels of 3,4-dihydroxybutyrate. Further randomized controlled trials (RCTs) are warranted to validate this conclusion.

Genomic and Metagenomic Insights into the Distribution of Nicotine-degrading Enzymes in Human Microbiota.

Introduction: Nicotine degradation is a new strategy to block nicotine-induced pathology. The potential of human microbiota to degrade nicotine has not been explored. Aims: This study aimed to uncover the genomic potentials of human microbiota to degrade nicotine. Methods: To address this issue, we performed a systematic annotation of Nicotine-Degrading Enzymes (NDEs) from genomes and metagenomes of human microbiota. A total of 26,295 genomes and 1,596 metagenomes for human microbiota were downloaded from public databases and five types of NDEs were annotated with a custom pipeline. We found 959 NdhB, 785 NdhL, 987 NicX, three NicA1, and three NicA2 homologs. Results: Genomic classification revealed that six phylum-level taxa, including Proteobacteria, Firmicutes, Firmicutes_A, Bacteroidota, Actinobacteriota, and Chloroflexota, can produce NDEs, with Proteobacteria encoding all five types of NDEs studied. Analysis of NicX prevalence revealed differences among body sites. NicX homologs were found in gut and oral samples with a high prevalence but not found in lung samples. NicX was found in samples from both smokers and non-smokers, though the prevalence might be different. Conclusion: This study represents the first systematic investigation of NDEs from the human microbiota, providing new insights into the physiology and ecological functions of human microbiota and shedding new light on the development of nicotine-degrading probiotics for the treatment of smoking-related diseases.

Spatial Variation of the Gastrointestinal Microbiota in Response to Long-Term Administration of Vonoprazan in Mice With High Risk of Gastric Cancer.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is superior to traditional proton pump inhibitor (PPI) in acid suppression and has been approved in the treatment of acid-related disorders. Accumulating evidence suggest associations between PPI use and gut microbiota, yet the effect of vonoprazan on GI microbiota is obscure. METHODS: Transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer (GC) were administered vonoprazan by gavage every other day for 12 weeks. Stomachs were evaluated by histopathology, Ki-67 proliferation index, and inflammatory cytokines. The mucosal and lumen microbiota from stomach, jejunum, ileum, cecum, and feces were detected using 16S rRNA gene sequencing. RESULTS: Higher incidence of intestinal metaplasia and epithelial proliferation were observed in the vonoprazan group than that in the control mice. Vonoprazan also elevated the gastric expression of proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6. Each mice comprised a unique microbiota composition that was consistent across different niches. The structure of GI microbiota changed dramatically after vonoprazan treatment with the stomach being the most disturbed segment. Vonoprazan administration shifted the gut microbiota toward the enrichment of pathogenic Streptococcus, Staphylococcus, Bilophila, and the loss of commensal Prevotella, Bifidobacterium, and Faecalibacterium. Interestingly, compared to the controls, microbial interactions were weaker in the stomach while stronger in the jejunum of the vonoprazan group. CONCLUSIONS: Long-term vonoprazan treatment promoted gastric lesions in male INS-GAS mice, with the disequilibrium of GI microbiome. The clinical application of vonoprazan needs to be judicious particularly among those with high risk of GC.

Neuroprotective Effects Exerted by a Combination of Selected Lactic Acid Bacteria in a Mouse Parkinsonism Model under Levodopa-Benserazide Treatment.

Alterations of the microbiota-gut-brain axis has been associated with intestinal and neuronal inflammation in Parkinson's disease (PD). The aim of this work was to study some mechanisms associated with the neuroprotective effect of a combination (MIX) of lactic acid bacteria (LAB) composed by Lactiplantibacillus plantarum CRL2130 (riboflavin overproducing strain), Streptococcus thermophilus CRL808 (folate producer strain), and CRL807 (immunomodulatory strain) in cell cultures and in a chronic model of parkinsonism induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in aged mice, and under levodopa-benserazide treatment. In vitro, N2a differentiated neurons were exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and treated with intracellular bacterial extracts or with conditioned media from BV-2 cells exposed to the bacterial extracts. In vivo, motor skills, tyrosine hydrolase (TH) in brain and cytokine concentrations in serum and in brain were evaluated. The study of the faecal microbiota and the histology of the small intestine was also performed. The results showed that the neuroprotective effect associated with LAB MIX administration did not interfere with levodopa-benserazide treatment. This effect could be associated with the antioxidant and immunomodulatory potential of the LAB selected in the MIX, and was associated with the significant improvement in the motor tests and a higher number of TH + cells in the brain. In addition, LAB MIX administration was associated with modulation of the immune response. LAB administration decreased intestinal damage with an increase in the villus length /crypt depth ratio. Finally, the administration of the LAB MIX in combination with levodopa-benserazide treatment was able to partially revert the intestinal dysbiosis observed in the model, showing greater similarity to the profiles of healthy controls, and highlighting the increase in the Lactobacillaceae family. Different mechanisms of action would be related to the protective effect of the selected LAB combination which has the potential to be evaluated as an adjuvant for conventional PD therapies.

Gut microbiota causally affects drug-induced liver injury via plasma metabolites: a Mendelian randomization study.

Background: The gut microbiota and plasma metabolites play important roles in the progression of drug-induced liver injury (DILI). We investigated the causal associations between the gut microbiota, plasma metabolome, and DILI. Methods: The summary data for gut microbiota (n = 18,340), plasma metabolome (n = 8,299), and DILI (n = 366,838) were obtained from the large genome-wide association studies. A two-sample Mendelian randomization was performed to explore the associations between the gut microbiota, plasma metabolome, and DILI. Additionally, a two-step Mendelian randomization was performed to explore the potential metabolites. Results: Five taxa were causally associated with DILI, including Oscillospira [odds ratio (OR) = 2.257, 95% confidence interval (CI) = 1.110-4.590], Blautia (OR = 2.311, 95% CI = 1.010-5.288), Roseburia (OR = 2.869, 95% CI = 1.429-5.761), Fusicatenibacter (OR = 1.995, 95% CI = 1.024-3.890), and Prevotella 7 (OR = 1.549, 95% CI = 1.065-2.253). Moreover, 53 metabolites were causally associated with DILI. After mediation analysis, four taxa were found to affect DILI through five mediation metabolites. N6-carbamoylthreonyladenosine mediated the effect of Blautia on DILI. Acetylcarnitine mediated the effect of Fusicatenibacter on DILI. In addition, 4-cholesten-3-one mediated the effect of Prevotella 7 on DILI. Furthermore, 5,6-dihydrothymine levels and the salicylate-to-citrate ratio mediated the effect of Oscillospira on DILI. Conclusion: We found that the gut microbiota could affect DILI through plasma metabolites, which could serve as potential biomarkers for risk stratification and elucidate underlying mechanisms for further investigation of DILI.

Unraveling the gut microbiota's role in salt-sensitive hypertension: current evidences and future directions.

The gut microbiota plays a pivotal role in both maintaining human health and in the pathogenesis of diseases. Recent studies have brought to light the significant correlation between gut microbiota and hypertension, particularly focusing on its role in the development and advancement of SSH, a subtype characterized by elevated blood pressure in response to high salt consumption. The complexity of SSH's etiology is notable, with dysbiosis of the gut microbiome identified as a crucial contributing factor. The gut microbiota participates in the occurrence and development of SSH by affecting the host's immune system, metabolic function, and neuromodulation. Investigations have demonstrated that the gut microbes regulate the development of SSH by regulating the TH17 axis and the activity of immune cells. Moreover, microbial metabolites, such as short-chain fatty acids, are implicated in blood pressure regulation and affect the development of SSH. There is evidence to show that the composition of the gut microbiome can be altered through prebiotic interventions so as to prevent and treat SSH. This review aims to concisely sum up the role of gut microbiota in SSH and to discuss pertinent therapeutic strategies and clinical implications, thereby providing a valuable reference for further research and clinical practice in this area.

Intravaginal probiotics before embryo transfer do not improve pregnancy rates in recurrent implantation failure cases: An RCT.

Background: Considering the considerable influence of the vaginal microbiome on endometrial receptivity and embryo implantation, we hypothesized that cases of recurrent implantation failure (RIF) might benefit from the intravaginal probiotic administration. Objective: Evaluation of the effects of intravaginal probiotic administration before frozen embryo transfer (FET) on the rates of pregnancy and the status of vaginal lactobacillary flora in cases of RIF. Materials and Methods: This was a randomized, parallel-group, clinical trial conducted at an infertility clinic in Tehran, Iran between January 2021 and September 2022. A total of 166 reproductive-aged women with a history of unexplained RIF were randomly assigned to either the probiotic group or the control group (n = 83/each group). The probiotic group received intravaginal probiotics (LactoVagⓇ) daily for 2 wk from the second day of the menstrual cycle along with the routine treatment of FET. The control group received only the routine treatment of FET. The primary outcome was the chemical pregnancy rate, and the secondary outcomes were the clinical pregnancy rate and the status of vaginal lactobacillary flora. Results: A total of 163 participants were included in the final analysis. The probiotic group had a slightly higher chemical pregnancy rate than the control group (39.02% vs. 33.33%), but the difference was not statistically significant (risk ratio: 1.71, 95% CI: 0.77-1.76; p = 0.449). The clinical pregnancy rate was also non-significantly higher in the probiotic group than the control group (37.80% vs. 33.33%; RR: 1.14, 95% CI: 0.76-1.74; p = 0.623). Conclusion: Intravaginal probiotic administration did not significantly improve the pregnancy rates in RIF cases undergoing FET. Further studies are needed to explore the optimal dose, duration, and timing of probiotic administration, as well as the mechanisms of action and the potential adverse effects of probiotics on the vaginal microbiome and the implantation process.