Gut microbiota induced epigenetic modifications in the non-alcoholic fatty liver disease pathogenesis.

Non-alcoholic fatty liver disease (NAFLD) represents a growing global health concern that can lead to liver disease and cancer. It is characterized by an excessive accumulation of fat in the liver, unrelated to excessive alcohol consumption. Studies indicate that the gut microbiota-host crosstalk may play a causal role in NAFLD pathogenesis, with epigenetic modification serving as a key mechanism for regulating this interaction. In this review, we explore how the interplay between gut microbiota and the host epigenome impacts the development of NAFLD. Specifically, we discuss how gut microbiota-derived factors, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), can modulate the DNA methylation and histone acetylation of genes associated with NAFLD, subsequently affecting lipid metabolism and immune homeostasis. Although the current literature suggests a link between gut microbiota and NAFLD development, our understanding of the molecular mechanisms and signaling pathways underlying this crosstalk remains limited. Therefore, more comprehensive epigenomic and multi-omic studies, including broader clinical and animal experiments, are needed to further explore the mechanisms linking the gut microbiota to NAFLD-associated genes. These studies are anticipated to improve microbial markers based on epigenetic strategies and provide novel insights into the pathogenesis of NAFLD, ultimately addressing a significant unmet clinical need.

A Small-Molecule Ratiometric Photoacoustic Probe for the High-Spatiotemporal-Resolution Imaging of Copper(II) Dynamics in the Mouse Brain.

Copper dysmetabolism is associated with various neurodegenerative disorders, making high-spatiotemporal-resolution imaging of Cu2+ in the brain essential for understanding the underlying pathophysiological processes. Nevertheless, the current probes encounter obstacles in crossing the blood-brain barrier (BBB) and providing high-spatial-resolution in deep tissues. Herein, we present a photoacoustic probe capable of imaging Cu2+ dynamics in the mouse brain with high-spatiotemporal-resolution. The probe demonstrates selective ratiometric and reversible responses to Cu2+ , while also efficiently crossing the BBB. Using the probe as the imaging agent, we successfully visualized Cu2+ in the brain of Parkinson's disease (PD) model mouse with a remarkable micron-level resolution. The imaging results revealed a significant increase in Cu2+ levels in the cerebral cortex as PD progresses, highlighting the close association between Cu2+ alternations in the region and the disease. We also demonstrated that the probe can be used to monitor changes in Cu2+ distribution in the PD model mouse brain during L-dopa intervention. Mechanism studies suggest that the copper dyshomeostasis in the PD mouse brain was dominated by the expression levels of divalent metal transporter 1. The application of our probe in imaging Cu2+ dynamics in the mouse brain offers valuable insights into the copper-related molecular mechanisms underlying neurodegenerative diseases.

Altered oral microbiota and immune dysfunction in Chinese elderly patients with schizophrenia: a cross-sectional study.

Schizophrenia (SZ) is a complex psychiatric neurodevelopmental disorder with uncertain etiology and pathogenesis. Increasing evidence has recognized the key role of the gut microbiota in SZ. However, few studies have investigated the potential link between oral microbiota and SZ. We studied the tongue coating microbiota and inflammatory profiles of 118 elderly SZ patients and 97 age-matched healthy controls using Illumina MiSeq sequencing and multiplex immunoassays, respectively. Reduced α-diversity, along with a significant difference in ß-diversity, were observed in patients with SZ. We have identified SZ-associated oral dysbiosis, characterized by increased Streptococcus and Fusobacterium, as well as decreased Prevotella and Veillonella. These differential genera could potentially serve as biomarkers for SZ, either alone or in combination. Additionally, an elevated Streptococcus/Prevotella ratio could indicate oral dysbiosis. These differential genera formed two distinct clusters: Streptococcus-dominated and Prevotella-dominated, which exhibited different correlations with the altered immunological profiles. Furthermore, we also observed disruptions in the inferred microbiota functions in SZ-associated microbiota, particularly in lipid and amino acid metabolism. Our study provides novel insights into the characteristics of tongue coating microbiota and its associations with immunological disturbances in elderly SZ patients, which offer new targets for the diagnosis and treatment of SZ in the elderly.

Fecal Microbiota Underlying the Coexistence of Schizophrenia and Multiple Sclerosis in Chinese Patients.

Both schizophrenia (SZ) and multiple sclerosis (MS) affect millions of people worldwide and impose a great burden on society. Recent studies indicated that MS elevated the risk of SZ and vice versa, whereas the underlying pathological mechanisms are still obscure. Considering that fecal microbiota played a vital role in regulating brain functions, the fecal microbiota and serum cytokines from 90 SZ patients and 71 age-, gender-, and BMI-matched cognitively normal subjects (referred as SZC), 22 MS patients and 33 age-, gender-, and BMI-matched healthy subjects (referred as MSC) were analyzed. We found that both diseases demonstrated similar microbial diversity and shared three differential genera, including the down-regulated Faecalibacterium, Roseburia, and the up-regulated Streptococcus. Functional analysis indicated that the three genera were involved in pathways such as "carbohydrate metabolism" and "amino acid metabolism." Moreover, the variation patterns of serum cytokines associated with MS and SZ patients were a bit different. Among the six cytokines perturbed in both diseases, TNF-α increased, while IL-8 and MIP-1α decreased in both diseases. IL-1ra, PDGF-bb, and RANTES were downregulated in MS patients but upregulated in SZ patients. Association analyses showed that Faecalibacterium demonstrated extensive correlations with cytokines in both diseases. Most notably, Faecalibacterium correlated negatively with TNF-α. In other words, fecal microbiota such as Faecalibacterium may contribute to the coexistence of MS and SZ by regulating serum cytokines. Our study revealed the potential roles of fecal microbiota in linking MS and SZ, which paves the way for developing gut microbiota-targeted therapies that can manage two diseases with a single treat.

Akkermansia muciniphila in neuropsychiatric disorders: friend or foe?

An accumulating body of evidence suggests that the bacterium Akkermansia muciniphila exhibits positive systemic effects on host health, mainly by improving immunological and metabolic functions, and it is therefore regarded as a promising potential probiotic. Recent clinical and preclinical studies have shown that A. muciniphila plays a vital role in a variety of neuropsychiatric disorders by influencing the host brain through the microbiota-gut-brain axis (MGBA). Numerous studies observed that A. muciniphila and its metabolic substances can effectively improve the symptoms of neuropsychiatric disorders by restoring the gut microbiota, reestablishing the integrity of the gut mucosal barrier, regulating host immunity, and modulating gut and neuroinflammation. However, A. muciniphila was also reported to participate in the development of neuropsychiatric disorders by aggravating inflammation and influencing mucus production. Therefore, the exact mechanism of action of A. muciniphila remains much controversial. This review summarizes the proposed roles and mechanisms of A. muciniphila in various neurological and psychiatric disorders such as depression, anxiety, Parkinson's disease, Alzheimer's disease, multiple sclerosis, strokes, and autism spectrum disorders, and provides insights into the potential therapeutic application of A. muciniphila for the treatment of these conditions.

Probiotics for the treatment of depression and its comorbidities: A systemic review.

Depression is one of the most common psychiatric conditions, characterized by significant and persistent depressed mood and diminished interest, and often coexists with various comorbidities. The underlying mechanism of depression remain elusive, evidenced by the lack of an appreciate therapy. Recent abundant clinical trials and animal studies support the new notion that the gut microbiota has emerged as a novel actor in the pathophysiology of depression, which partakes in bidirectional communication between the gut and the brain through the neuroendocrine, nervous, and immune signaling pathways, collectively known as the microbiota-gut-brain (MGB) axis. Alterations in the gut microbiota can trigger the changes in neurotransmitters, neuroinflammation, and behaviors. With the transition of human microbiome research from studying associations to investigating mechanistic causality, the MGB axis has emerged as a novel therapeutic target in depression and its comorbidities. These novel insights have fueled idea that targeting on the gut microbiota may open new windows for efficient treatment of depression and its comorbidities. Probiotics, live beneficial microorganisms, can be used to modulate gut dysbiosis into a new eubiosis and modify the occurrence and development of depression and its comorbidities. In present review, we summarize recent findings regarding the MGB axis in depression and discuss the potential therapeutic effects of probiotics on depression and its comorbidities.

Clinical Features and Skin Microbiome of Tinea Scrotum: An Observational Study of 113 Cases in China.

BACKGROUND: The scrotum is considered as an uncommon site for tinea, hence there is a lack of knowledge about the clinical characteristics, pathogenic agents and the skin microbiome changes of tinea scrotum. OBJECTIVE: We sought to analyze the clinical features, pathogenic agents and skin microbiome of tinea scrotum. METHODS: A two-center prospective observational study was carried out in outpatient dermatology clinics in Zhejiang, China, from September 2017 to September 2019. The diagnosis of tinea scrotum was confirmed by direct microscopy. Clinical and mycological data were collected. The composition of microbial communities of patients with tinea scrotum was analyzed and compared with healthy controls. RESULTS: A total of 113 patients with tinea scrotum were included. Tinea scrotum was either presented with isolated lesions (9/113, 8.0%) or accompanied by tinea of other sites (104/113, 92.0%). Tinea cruris was detected in 101 cases (89.38%). Fungal culture was positive in 63 cases, among which Trichophyton rubrum was grown in 60 cases (95.2%) and Nannizzia gypsea was cultured in 3 cases (4.8%). The skin microbiome in scrotum lesions from 18 patients showed increased abundance of Trichophyton compared with 18 healthy individuals, while Malassezia was decreased. No significant difference in bacterial diversity was found. CONCLUSIONS: Tinea scrotum was often companied by superficial fungal infections of other skin sites, with tinea cruris being the most common condition. Instead of N. gypsea, T. rubrum was the most frequently identified pathogen for tinea scrotum. In general, tinea scrotum exhibited changes in the fungal communities of the skin with increased Trichophyton and decreased Malassezia abundance.

Alterations of the fecal and vaginal microbiomes in patients with systemic lupus erythematosus and their associations with immunological profiles.

Background: Exploring the human microbiome in multiple body niches is beneficial for clinicians to determine which microbial dysbiosis should be targeted first. We aimed to study whether both the fecal and vaginal microbiomes are disrupted in SLE patients and whether they are correlated, as well as their associations with immunological features. Methods: A group of 30 SLE patients and 30 BMI-age-matched healthy controls were recruited. Fecal and vaginal samples were collected, the 16S rRNA gene was sequenced to profile microbiomes, and immunological features were examined. Results: Distinct fecal and vaginal bacterial communities and decreased microbial diversity in feces compared with the vagina were found in SLE patients and controls. Altered bacterial communities were found in the feces and vaginas of patients. Compared with the controls, the SLE group had slightly lower gut bacterial diversity, which was accompanied by significantly higher bacterial diversity in their vaginas. The most predominant bacteria differed between feces and the vagina in all groups. Eleven genera differed in patients' feces; for example, Gardnerella and Lactobacillus increased, whereas Faecalibacterium decreased. Almost all the 13 genera differed in SLE patients' vaginas, showing higher abundances except for Lactobacillus. Three genera in feces and 11 genera in the vagina were biomarkers for SLE patients. The distinct immunological features were only associated with patients' vaginal microbiomes; for example, Escherichia-Shigella was negatively associated with serum C4. Conclusions: Although SLE patients had fecal and vaginal dysbiosis, dysbiosis in the vagina was more obvious than that in feces. Additionally, only the vaginal microbiome interacted with patients' immunological features.

Prognostic effects of the gastric mucosal microbiota in gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors with a high incidence and mortality. Microbiota play a significant role in human health and disease. We aimed to investigate the prognostic value of the gastric microbiota in different stomach microhabitats. We used our previously published 16S rRNA gene sequence data. We retrospectively enrolled a cohort of 132 patients with GC with complete prognostic information and selected 78 normal tissues, 49 peritumoral tissues, and 112 tumoral tissues for microbiota analysis. Patients with different prognoses showed different gastric microbiota compositions and diversity. The association network of the abundant gastric microbiota was more complicated in patients with poor prognoses. In the peritumoral microhabitat of patients with good prognoses, Helicobacter was significantly increased, whereas Halomonas and Shewanella were significantly decreased relative to that in the peritumoral microhabitat of patients with poor prognoses. PiCRUSt analysis revealed that the peritumoral microbiota had more different Kyoto Encyclopedia of Genes and Genomes pathways than did the tumoral and normal microbiota. This study evaluated the long-term prognostic value of the gastric mucosal microbiota in patients with GC. These findings suggested that the characteristic alterations of the gastric mucosal microbiota may be markers for clinical outcomes in these patients.

Exploring the gut mycobiome: differential composition and clinical associations in hypertension, chronic kidney disease, and their comorbidity.

Background: Hypertension (HTN) and chronic kidney disease (CKD) pose significant global health challenges and often coexist, amplifying cardiovascular risks. Recent attention has turned to the gut mycobiome as a potential factor in their pathophysiology. Our study sought to examine the gut fungal profile in individuals with HTN, CKD, and the concurrent HTN+CKD condition, investigating its connections with serum cytokines, renal function, and blood pressure. Methods and materials: We investigated three distinct participant groups: a cohort of 50 healthy controls (HC), 50 individuals diagnosed with HTN-only, and 50 participants suffering from both HTN and CKD (HTN+CKD). To facilitate our research, we gathered fecal and blood samples and conducted a comprehensive analysis of serum cytokines. Moreover, fungal DNA extraction was conducted with meticulous care, followed by sequencing of the Internal Transcribed Spacer (ITS) region. Results: HTN+CKD patients displayed distinctive fungal composition with increased richness and diversity compared to controls. In contrast, HTN-only patients exhibited minimal fungal differences. Specific fungal genera were notably altered in HTN+CKD patients, characterized by increased Apiotrichum and Saccharomyces levels and reduced Candida abundance. Our correlation analyses revealed significant associations between fungal genera and serum cytokines. Moreover, certain fungal taxa, such as Apiotrichum and Saccharomyces, exhibited positive correlations with renal function, while others, including Septoria, Nakaseomyces, and Saccharomyces, were linked to blood pressure, particularly diastolic pressure. Conclusion: Gut mycobiome dysbiosis in individuals with comorbid HTN and CKD differs significantly from that observed in HTN-only and healthy controls. The interactions between serum cytokines, renal function, and blood pressure emphasize the potential impact of the fungal microbiome on these conditions. Additional research is required to clarify the underlying mechanisms and identify therapeutic opportunities associated with mycobiome dysbiosis in HTN and CKD.

Comparative analysis of the lung microbiota in patients with respiratory infections, tuberculosis, and lung cancer: A preliminary study.

Recent evidence suggests that lung microbiota can be recognized as one of the ecological determinants of various respiratory diseases. However, alterations in the lung microbiota and associated lung immunity in these respiratory diseases remain unclear. To compare the lung microbiota and lung immune profiles in common respiratory diseases, a total of 78 patients were enrolled in the present study, including 21 patients with primary pulmonary tuberculosis (PTB), eight patients with newly diagnosed lung cancer (LC), and 49 patients with community-acquired pneumonia (CAP). Bronchoalveolar lavage fluid (BALF) was collected for microbiota and cytokine analyses. With MiSeq sequencing system, increased bacterial alpha-diversity and richness were observed in patients with LC than in those with PTB and CAP. Linear discriminant analysis effect size revealed that CAP-associated pulmonary microbiota were significantly different between the PTB and LC groups. More key functionally different genera were found in the PTB and LC groups than in the CAP group. The interaction network revealed stronger positive and negative correlations among these genera in the LC group than in the other two groups. However, increased BALF cytokine profiles were observed in the PTB group than in the other two groups, while BALF cytokines were correlated with key functional bacteria. This comparative study provides evidence for the associations among altered lung microbiota, BALF inflammation, and different respiratory disorders, which provides insight into the possible roles and mechanisms of pulmonary microbiota in the progression of respiratory disorders.

Osteopontin Exacerbates High-Fat Diet-Induced Metabolic Disorders in a Microbiome-Dependent Manner.

The gut microbiome is involved in metabolic disorders. Osteopontin (OPN), as a key cytokine, contributes to various inflammation-related diseases. The underlying role of OPN in the microbiome remains poorly understood. Here, we investigated whether OPN could modulate metabolic disorders by affecting gut microbiota. In our present study, we found that the expression of OPN was elevated in individuals with obesity compared to that observed in healthy controls. There was a positive correlation between plasma OPN levels and body mass index (BMI) in humans. Moreover, OPN significantly exacerbated lipid accumulation and metabolic disorders in high-fat diet (HFD)-fed mice. Importantly, OPN significantly aggravated HFD-induced gut dysbiosis with a key signature profile. Fecal microbiota transplantation also supported the role of OPN in HFD-induced metabolic disorders in a microbiota-dependent manner. Moreover, the microbiome shift of OPN-deficient mice would be compensated to resemble those of wild-type mice by feeding with either OPN-containing milk or recombinant OPN protein in vivo. Furthermore, metagenomic analysis showed that OPN induced a higher abundance of Dorea and a lower abundance of Lactobacillus, which were positively and negatively correlated with body weight, respectively. Indeed, the abundance of Dorea was significantly decreased after Lactobacillus administration, suggesting that OPN may regulate the intestinal abundance of Dorea by reducing the colonization of Lactobacillus. We further confirmed that OPN decreased the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. This study suggested that OPN could exacerbate HFD-induced metabolic dysfunctions through the OPN-induced alteration of the gut microbiome. Therefore, OPN could be a potential therapeutic target for metabolic syndrome. IMPORTANCE Gut microbiota are involved in metabolic disorders. However, microbiome-based therapeutic interventions are not always effective, which might be due to interference of the host factors. Here, we identified a strong positive correlation between OPN levels and BMI in humans. Next, we confirmed that OPN could aggravate high-fat diet-induced metabolic disorders in mice. Importantly, we found that fecal microbiota transplantation from OPN-deficient mice significantly alleviated metabolic disorders in WT mice. OPN directly induces the remodeling of the gut microbiota both in vitro and in vivo. These findings indicate that OPN could contribute to metabolic disorders by inducing an alteration of gut microbiota. OPN regulated the relative abundance of Lactobacillus by decreasing the adhesion of Lactobacillus to intestinal epithelial cells through the Notch signaling pathway. These data identify OPN as a potential pharmaceutical target for weight control and for the treatment of metabolic disorders.

Changes in fecal microbiota composition and the cytokine expression profile in school-aged children with depression: A case-control study.

Depression in childhood negatively affects the growth and development, school performance, and peer or family relationships of affected children, and may even lead to suicide. Despite this, its etiology and pathophysiology remain largely unknown. Increasing evidence supports that gut microbiota plays a vital role in the development of childhood depression. However, little is known about the underlying mechanisms, as most clinical studies investigating the link between gut microbiota and depression have been undertaken in adult cohorts. In present study, a total of 140 school-aged children (6-12 years) were enrolled, including 92 with depression (male/female: 42/50) and 48 healthy controls (male/female: 22/26) from Lishui, Zhejiang, China. Illumina sequencing of the V3-V4 region of the 16S rRNA gene was used to investigate gut microbiota profiles while Bio-Plex Pro Human Cytokine 27-plex Panel was employed to explore host immune response. We found that, compared with healthy controls, children with depression had greater bacterial richness and altered ß-diversity. Pro-inflammatory genera such as Streptococcus were enriched in the depression group, whereas anti-inflammatory genera such as Faecalibacterium were reduced, as determined by linear discriminant analysis effect size. These changes corresponded to altered bacterial functions, especially the production of immunomodulatory metabolites. We also identified the presence of a complex inflammatory condition in children with depression, characterized by increased levels of pro-inflammatory cytokines such as IL-17 and decreased levels of anti-inflammatory cytokines such as IFN-γ. Correlation analysis demonstrated that the differential cytokine abundance was closely linked to changes in gut microbiota of children with depression. In summary, key functional genera, such as Streptococcus and Faecalibacterium, alone or in combination, could serve as novel and powerful non-invasive biomarkers to distinguish between children with depression from healthy ones. This study was the first to demonstrate that, in Chinese children with depression, gut microbiota homeostasis is disrupted, concomitant with the activation of a complex pro-inflammatory response. These findings suggest that gut microbiota might play an important role in the pathogenesis of depression in school-aged children, while key functional bacteria in gut may serve as novel targets for non-invasive diagnosis and patient-tailored early precise intervention in children with depression.

Correction to "Gut microbiota dysbiosis in Chinese children with type 1 diabetes mellitus: An observational study".

[This corrects the article on p. 2394 in vol. 27, PMID: 34040330.].

Gut Microbiota: A Novel Therapeutic Target for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis is involved in the occurrence, development and progression of PD. Numerous clinical trials have identified the characteristics of the changed gut microbiota profiles, and preclinical studies in PD animal models have indicated that gut dysbiosis can influence the progression and onset of PD via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels of α-synuclein fibrils, increasing oxidative stress, and decreasing neurotransmitter production. The gut microbiota can be considered promising diagnostic and therapeutic targets for PD, which can be regulated by probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, diet modifications, and Chinese medicine. This review summarizes the recent studies in PD-associated gut microbiota profiles and functions, the potential roles, and mechanisms of gut microbiota in PD, and gut microbiota-targeted interventions for PD. Deciphering the underlying roles and mechanisms of the PD-associated gut microbiota will help interpret the pathogenesis of PD from new perspectives and elucidate novel therapeutic strategies for PD.

Fecal Dysbiosis and Immune Dysfunction in Chinese Elderly Patients With Schizophrenia: An Observational Study.

Schizophrenia (SZ) is a severe neuropsychiatric disorder with largely unknown etiology and pathogenesis. Mounting preclinical and clinical evidence suggests that the gut microbiome is a vital player in SZ. However, the gut microbiota characteristics and its host response in elderly SZ patients are still not well understood. A total of 161 samples was collected, including 90 samples from elderly SZ patients and 71 samples from healthy controls. We explored the gut microbiota profiles targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with host immune response. Our data found that bacterial ß-diversity analyses could divide the SZ patients and healthy controls into two different clusters. The Linear discriminant analysis Effect Size (LEfSe) identified the compositional changes in SZ-associated bacteria, including Faecalibacterium, Roseburia, Actinomyces, Butyricicoccus, Prevotella and so on. In addition, the levels of pro-inflammatory cytokines such as IL-1ß were greatly increased in SZ patients while the levels of anti-inflammatory cytokines such as IFN-γ were markedly decreased. Correlation analysis suggested that these bacteria contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the SZ patients from healthy controls. Moreover, several predicted functional modules, including increased lipopolysaccharide biosynthesis, folate biosynthesis, lipoic acid metabolism, and decreased bile acid biosynthesis, fatty acid biosynthesis in SZ-associated microbiota, could be utilized by the bacteria to produce immunomodulatory metabolites. This study, for the first time, demonstrated the structural and functional dysbiosis of the fecal microbiota in Chinese elderly SZ patients, suggesting the potential for using gut key functional bacteria for the early, non-invasive diagnosis of SZ, personalized treatment, and the development of tailor-made probiotics designed for Chinese elderly SZ patients.

[Dynamic Microbial Shifts and Functional Analysis of Saliva Microbial Communities with Caries Children].

Objective: To observe the dynamic changes in the salivary microbiota of children with dental caries and those who were caries-free and to analyze the functional differences in the oral microecology of the two groups during the course of sugar metabolism and the synthesis and transport of multiple amino acids. Methods: Ten children with dental caries and 10 caries-free children were enrolled. We employed Illumina metagenomics technology to analyze the composition and function of salivary microbiome in children with and without caries. Six months later, PacBio single-molecule long-read sequencing technology was used to analyze the changes over time in the oral microbial communities of the two groups. We studied the patterns of change in the oral microbial communities under diseased or healthy conditions and attempted to offer a comprehensive interpretation of children's oral microbiota in terms of its composition and functions. Results: The composition of the oral microbiota of children with or without dental caries changed significantly over time. At the phylum level, changing trends in the salivary microbial communities of children with dental caries were in line with those in caries-free children. In these microbial communities, increased proportions of Firmicutes and decreased proportions of Actinobacteria and Bacteroidetes were found in the two groups. At the genus level, however, the two groups showed significantly different changes of the salivary microbial communities. Upward trends in the abundance of Lactobacillus, Methylobacterium, and Megasphaera were found in the caries group, while the abundance of these genera in the caries-free group showed downward trends. At the species level, L. fermentum, L. gasseri, L. oris, S. downei, and some other species belonging to the genus Lactobacillus showed upward trends in the saliva of children with caries, while they consistently stayed at a relative low level of abundance in caries-free children. The abundance of S. gordonii and S. mutans decreased to a certain extent in children with dental caries, but the abundance of S. gordonii and S. mutans in caries-free children were always at a low level. Species such as S. mutans and C. gracilis were positively correlated to the sum of decayed, missing and filled teeth (dmft), while N. flavescens was negatively correlated to dmft. gltA, icd, and mqo, the key genes related to tricarboxylic acid (TCA) cycle, gudB, a glutamate synthesis-related gene, and argAB/C/J, arginine synthesis-related genes, were significantly increased in caries-free children. In addition, the abundance of the NADH dehydrogenase-related gene nuoB/C/D/E/H/I/J/K/L/M in the electron transport chain increased significantly in caries-free children. Conclusion: Dynamic changes were found in the oral microbiota of children with or without caries. The trends of microbial shifts over time were associated with the oral health status. Oxidative phosphorylation and the synthesis and transport of amino acids such as glutamate and arginine in the oral microecology were more active in caries-free children.

Roles of Plasmacytoid Dendritic Cells in Gastric Cancer.

Gastric cancer (GC) is the fifth most common neoplasm and the third most deadly cancer in humans worldwide. Helicobacter pylori infection is the most important causative factor of gastric carcinogenesis, and activates host innate and adaptive immune responses. As key constituents of the tumor immune microenvironment, plasmacytoid dendritic cells (pDCs) are increasingly attracting attention owing to their potential roles in immunosuppression. We recently reported that pDCs have vital roles in the development of immunosuppression in GC. Clarifying the contribution of pDCs to the development and progression of GC may lead to improvements in cancer therapy. In this review, we summarize current knowledge regarding immune modulation in GC, especially the roles of pDCs in GC carcinogenesis and treatment strategies.

Secreted phosphoprotein 1 as a potential prognostic and immunotherapy biomarker in multiple human cancers.

Secreted phosphoprotein 1 (SPP1) is involved in immune regulation, cell survival, and tumor progression. Studies have demonstrated that SPP1 plays an important role in certain individual tumors. However, the expression profile and oncogenic features of SPP1 in diverse cancers are remaining unknown. Therefore, we performed a comprehensive analysis using The Cancer Genome Atlas (TCGA) database. Raw data of 33 cancer types were download from the University of California Santa Cruz (UCSC) Xena website. The expression of SPP1 and its relationship with tumor prognosis, immune invasion, tumor microenvironment, and immunotherapy were analyzed using the R language. The function analysis was conducted using Gene Set Enrichment Analysis (GSEA). The oncogenic features of SPP1 was validated by wound-healing assay and EdU staining assay. SPP1 highly expressed in most cancers. The expression of SPP1 was significant related to prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint genes, suggested that SPP1 plays an essential role in the tumor immune microenvironment and immune cell infiltration. The immune/stromal scores correlated positively with the SPP1 expression, and the relationship was affected by tumor heterogeneity and immunotherapy. In addition, SPP1 could predict the response of tumor immunotherapy. Functional analysis revealed the SPP1-associated terms and pathways. Finally, SPP1 significantly elevated cell proliferation and migration in A549, Huh7, HT-29, A2780 tumor cell lines. In conclusion, this study indicated that SPP1 involved in tumorigenesis, tumor progression, and regulated tumor immune microenvironment, revealing SPP1 might be a potential target for evaluating prognosis and immunotherapy in multiple cancers.

Gut microbiota and aging.

Aging is characterized by the functional decline of tissues and organs and increased risk of aging-associated disorders, which pose major societal challenges and are a public health priority. Despite extensive human genetics studies, limited progress has been made linking genetics with aging. There is a growing realization that the altered assembly, structure and dynamics of the gut microbiota actively participate in the aging process. Age-related microbial dysbiosis is involved in reshaping immune responses during aging, which manifest as immunosenescence (insufficiency) and inflammaging (over-reaction) that accompany many age-associated enteric and extraenteric diseases. The gut microbiota can be regulated, suggesting a potential target for aging interventions. This review summarizes recent findings on the physiological succession of gut microbiota across the life-cycle, the roles and mechanisms of gut microbiota in healthy aging, alterations of gut microbiota and aging-associated diseases, and the gut microbiota-targeted anti-aging strategies.