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.

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.

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.

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.

Gut microbiota dysbiosis associated with plasma levels of Interferon-γ and viral load in patients with acute hepatitis E infection.

Few studies have focused on the effect of hepatitis E virus (HEV) infection on gut microbiota. To explore the relationship between changes in gut microbiota and inflammatory factors and viral load, we conducted a comparative study of 33 patients with acute hepatitis E (AHE) patients and 25 healthy controls (HCs) using high-throughput 16S ribosomal ribonucleic acid gene sequencing. Shannon and Simpson's indices showed no significant differences in bacterial diversity between the AHE and HCs groups. Proteobacteria, Gammaproteobacteria, and Enterobacteriaceae were most abundant in the AHE group, which contributed to the difference between the gut microbiota of the AHE and HCs groups, and the same difference between the HEV-RNA-positive and HEV-RNA-negative groups. Functional prediction analysis showed that ribosome, purine metabolism, and two-component system were the top three pathways. Compared with the AHE group with normal interferon (IFN)-γ, Proteobacteria, Gammaproteobacteria, Xanthomonadaceae, and Enterobacteriaceae were more abundant in the high-IFN-γ group. The abundance of Gammaproteobacteria was positively correlated with the level of serum alanine transaminase and total bilirubin. The abundance of Gammaproteobacteria could discriminate AHE patients from HCs, and could better predict the severity of AHE patients. We believe that our findings will contribute toward a novel treatment strategy for AHE.

Short-chain fatty acids-producing probiotics: A novel source of psychobiotics.

Psychobiotics-live microorganisms with potential mental health benefits, which can modulate the microbiota-gut-brain-axis via immune, humoral, neural, and metabolic pathways-are emerging as novel therapeutic options for the effective treatment of psychiatric disorders Recently, microbiome studies have identified numerous putative psychobiotic strains, of which short-chain fatty acids (SCFAs) producing bacteria have attracted special attention from neurobiologists. Recent studies have highlighted that SCFAs-producing bacteria such as Lactobacillus, Bifidobacterium and Clostridium have a very specific function in various psychiatric disorders, suggesting that these bacteria can be potential novel psychobiotics. SCFAs, potential mediators of microbiota-gut-brain axis, might modulate function of neurological processes. While the specific roles and mechanisms of SCFAs-producing bacteria of microbiota-targeted interventions on neuropsychiatric disease are largely unknown. This Review summarizes existing knowledge on the neuroprotective effects of the SCFAs-producing bacteria in neurological disorders via modulating microbiota-gut-brain axis and illustrate their possible mechanisms by which SCFAs-producing bacteria may act on these disorders, which will shed light on the SCFAs-producing bacteria as a promising novel source of psychobiotics.

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.

[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.

Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of Parkinson's disease via gut microbiota-GLP-1 pathway.

A connection between gut microbiota and Parkinson's disease (PD) indicates that dysbiosis of the gut microbiota might represent a risk factor for PD. Microbiota-targeted interventions, including probiotic Clostridium butyricum (Cb), have been recently shown to have favorable effects in PD by regulating microbiota-gut-brain axis. However, the potential beneficial roles and its mechanisms of Cb on PD were still unknown. Male C57BL/6 mice were subjected to a PD model-induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and were treated intragastrically with Cb for 4 weeks. The motor functions were assessed by a series of behavioral tests including pole test, beam walking teat, forced swimming test and open field test. The dopaminergic neuron loss, synaptic plasticity and microglia activation, as well as the levels of colonic glucagon-like peptide-1 (GLP-1), colonic G protein-coupled receptors GPR41/43 and cerebral GLP-1 receptors were assessed. Gut microbial composition was assessed by 16S rRNA sequencing analysis. Our results showed that oral administration of Cb could improve motor deficits, dopaminergic neuron loss, synaptic dysfunction and microglia activation in the MPTP-induced mice. Meanwhile, Cb treatment could reverse the dysbiosis of gut microbiota and the decreased levels of colonic GLP-1, colonic GPR41/43 and cerebral GLP-1 receptor in the MPTP-induced mice. These findings indicated that the neuroprotective mechanism of Cb on PD might be related to the improvement of abnormal gut microbiota-gut-brain axis.

A Borondifluoride-Complex-Based Photothermal Agent with an 80 % Photothermal Conversion Efficiency for Photothermal Therapy in the NIR-II Window.

Small organic photothermal agents (SOPTAs) that absorb in the second near-infrared (NIR-II, 1000-1700 nm) window are highly desirable in photothermal therapy for their good biocompatibility and deeper tissue penetration. However, the design of NIR-II absorbing SOPTAs remains a great challenge. Herein, we report that molecular engineering of BF2 complex via strengthening the donor-acceptor conjugation and increasing the intramolecular motions is an efficient strategy to achieve NIR-II absorbing SOPTAs with high photothermal performance. Based on this strategy, a BF2 complex, BAF4, was designed and synthesized. BAF4 exhibits an intense absorption maximum at 1000 nm and negligible fluorescence. Notably, the nanoparticles of BAF4 achieve a high photothermal conversion efficiency value of 80 % under 1064 nm laser irradiation (0.75 W cm-2 ). In vitro and in vivo studies reveal the great potential of BAF4 nanoparticles in photoacoustic imaging-guided photothermal therapy in the NIR-II window.

Altered faecal microbiota on the expression of Th cells responses in the exacerbation of patients with hepatitis E infection.

Fulminant hepatitis E may lead to acute liver failure (ALF). Perturbations of intestinal microbiota are related to severe liver disease. To study the correlations between faecal microbiota and the occurrence and exacerbation of hepatitis E virus (HEV) infection, we characterized 24 faecal samples from 12 patients with acute hepatitis E (AHE) and 12 patients with HEV-ALF using high-throughput sequencing. We found both the alpha and beta diversity indices showed no significant differences between the AHE and HEV-ALF groups. Several predominant taxa were significantly different between the AHE and HEV-ALF groups. Most notably, the HEV-ALF group had increased levels of Gammaproteobacteria, Proteobacteria, Xanthomonadceae and Stenotrophomonas, but reduced levels of Firmicutes, Streptococcus, Subdoligranulum and Lactobacillus, compared with the AHE group. The levels of Lactobacillaceae and Gammaproteobacteria could be used to distinguish patients with HEV-ALF from those with AHE. In addition, the level of Th lymphocytes was significantly lower in the HEV-ALF group than in the AHE group. The relative abundances of Lactobacillaceae and Gammaproteobacteria were positively correlated with Th lymphocytes, serum international normalized ratio (INR) and hepatic encephalopathy severity. Moreover, surviving patients had higher levels of Lactobacillus mucosae than deceased patients. Our study demonstrated that the presence of altered faecal microbiota is associated with exacerbation of HEV infection; this finding may be useful for exploring the interactions among faecal microbiota, immune responses, mechanisms of infection and progression in patients with HEV, as well as for the development of novel diagnostic and therapeutic strategies.

Altered Profiles of Gut Microbiota in Klebsiella pneumoniae-Induced Pyogenic Liver Abscess.

Intestinal microbiota plays a crucial role in preventing the colonization and invasion by pathogens, and disruption of microbiota may cause opportunistic infections and diseases. Pathogens often have strategies to escape from the colonization resistance mediated by microbiota, but whether they also modulate the microbiota composition is still a topic of investigation. In the present study, we addressed this question using an opportunistic pathogen, Klebsiella pneumoniae serotype K1, which is known to cause pyogenic liver abscess (KLA) in about 30% of mice. We examined the effect of K. pneumoniae infection on cecal microbiota composition by performing high-throughput 454 pyrosequencing of the hypervariable V3-V4 regions of bacterial 16S rRNA gene. Our data revealed that K. pneumoniae inoculation substantially changed the cecal microbiota composition when analyzed at the phylum, order, and family levels. Most strikingly, the KLA-infected mice had significantly increased abundance of Bacteroidales and Enterobacteriales and decreased abundance of Lactobacillales and Eggerthellales. Furthermore, by comparing the infected mice with or without KLA disease symptoms, we identified specific microbiota changes associated with the KLA disease induction. Especially, the KLA group had dramatically decreased sequence identical to Lactobacillus compared with non-KLA mice. These findings suggest that the pathogenic process of KLA infection may involve alteration of microbiota compositions, particularly reduction in Lactobacillus.

ram1 gene, encoding a subunit of farnesyltransferase, contributes to growth, antifungal susceptibility to amphotericin B of Aspergillus fumigatus.

Farnesylation, which is catalyzed by farnesyltransferase, is an important posttranslational process. The function of farnesyltransferase has been previously explored in Cryptococcus neoformans and Candida albicans. Aspergillus fumigatus is an important human opportunistic fungal pathogen in immunocompromised patients. Here we discover the role of the ram1 gene, encoding the ß-subunit of farnesyltransferase in A. fumigatus, in the fungal growth and antifungal susceptibility. In this study the ram1 gene was disrupted using A. tumefaciens-mediated transformation. The morphology and radial growth of Δram1 were observed. Assays of disk diffusion and broth microdilution were used to determine the susceptibility of Δram1 mutant to commonly clinical used antifungals and the farnesyltransferase inhibitor manumycin A. Deletion of ram1 resulted in a reduced radial growth of A. fumigatus but did not affect the microscopic morphology. Δram1 showed increased susceptibility to the antifungal amphotericin B; however, its susceptibility to azoles and caspofungin was the same to that to the parental strain. Our data indicate that farnesyltransferase is a potential target for design new antifungal agents.

Maternal infection during pregnancy and risk of autism spectrum disorders: A systematic review and meta-analysis.

Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR=1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR=1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.

Altered fecal microbiota composition in patients with major depressive disorder.

Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

Altered fecal microbiota composition associated with food allergy in infants.

Increasing evidence suggests that perturbations in the intestinal microbiota composition of infants are implicated in the pathogenesis of food allergy (FA), while the actual structure and composition of the intestinal microbiota in human beings with FA remain unclear. Microbial diversity and composition were analyzed with parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V1-V3 regions in the feces of 34 infants with FA (17 IgE mediated and 17 non-IgE mediated) and 45 healthy controls. Here, we showed that several key FA-associated bacterial phylotypes, but not the overall microbiota diversity, significantly changed in infancy fecal microbiota with FA and were associated with the development of FA. The proportion of abundant Bacteroidetes, Proteobacteria, and Actinobacteria phyla were significantly reduced, while the Firmicutes phylum was highly enriched in the FA group (P < 0.05). Abundant Clostridiaceae 1 organisms were prevalent in infants with FA at the family level (P = 0.016). FA-enriched phylotypes negatively correlated with interleukin-10, for example, the genera Enterococcus and Staphylococcus. Despite profound interindividual variability, levels of 20 predominant genera were significantly different between the FA and healthy control groups (P < 0.05). Infants with IgE-mediated FA had increased levels of Clostridium sensu stricto and Anaerobacter and decreased levels of Bacteroides and Clostridium XVIII (P < 0.05). A positive correlation was observed between Clostridium sensu stricto and serum-specific IgE (R = 0.655, P < 0.001). The specific microbiota signature could distinguish infants with IgE-mediated FA from non-IgE-mediated ones. Detailed microbiota analysis of a well-characterized cohort of infants with FA showed that dysbiosis of fecal microbiota with several FA-associated key phylotypes may play a pathogenic role in FA.

Pyrosequencing analysis of oral microbiota shifting in various caries states in childhood.

Dental caries is one of the most prevalent childhood diseases worldwide, but little is known about the dynamic characteristics of oral microbiota in the development of dental caries. To investigate the shifting bacterial profiles in different caries states, 60 children (3-7-year-old) were enrolled in this study, including 30 caries-free subjects and 30 caries-active subjects. Supragingival plaques were collected from caries-active subjects on intact enamel, white spot lesions and carious dentin lesions. Plaques from caries-free subjects were used as a control. All samples were analyzed by 454 pyrosequencing based on 16S rRNA gene V1-V3 hypervariable regions. A total of 572,773 pyrosequencing reads passed the quality control and 25,444 unique phylotypes were identified, which represented 18 phyla and 145 genera. Reduced bacterial diversity in the cavitated dentin was observed as compared with the other groups. Thirteen genera (including Capnocytophaga, Fusobacterium, Porphyromonas, Abiotrophia, Comamonas, Tannerella, Eikenella, Paludibacter, Treponema, Actinobaculum, Stenotrophomonas, Aestuariimicrobium, and Peptococcus) were found to be associated with dental health, and the bacterial profiles differed considerably depending on caries status. Eight genera (including Cryptobacterium, Lactobacillus, Megasphaera, Olsenella, Scardovia, Shuttleworthia, Cryptobacterium, and Streptococcus) were increased significantly in cavitated dentin lesions, and Actinomyces and Corynebacterium were present at significant high levels in white spot lesions (P < 0.05), while Flavobacterium, Neisseria, Bergeyella, and Derxia were enriched in the intact surfaces of caries individuals (P < 0.05). Our results showed that oral bacteria were specific at different stages of caries progression, which contributes to informing the prevention and treatment of childhood dental caries.

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.

Pyrosequencing analysis of the human microbiota of healthy Chinese undergraduates.

BACKGROUND: Elucidating the biogeography of bacterial communities on the human body is critical for establishing healthy baselines from which to detect differences associated with disease; however, little is known about the baseline bacterial profiles from various human habitats of healthy Chinese undergraduates. RESULTS: Using parallel barcoded 454 pyrosequencing targeting on the 16S rRNA gene V3 region, the bacterial diversity of the nasopharynx, saliva, dominant hands, and feces were investigated from 10 healthy Chinese junior boarding undergraduates at Zhejiang University. The participants were 21-24 years of age with a body mass index (BMI) < 24 kg/m(2). A total of 156,717 high-quality pyrosequencing reads were obtained for evaluating bacterial diversity, which represented 29,887 unique phylotypes. The overall taxonomic distribution of the 16S rRNA gene-based amplicons demonstrated that these 4 habitats of the human body harbored distinct microbiota and could be divided into different clusters according to anatomic site, while the established patterns of bacterial diversity followed the human body habitat (feces, hands, saliva, and nasopharynx). Although significant inter-individual variation was observed, the healthy microbiota still shared a large number of phylotypes in each habitat, but not among the four habitats, indicating that a core microbiome existed in each healthy habitat. The vast majority of sequences from these different habitats were classified into different taxonmies that became the predominant bacteria of the healthy microbiota. CONCLUSIONS: We first established the framework of microbial communities from four healthy human habitats of the same participants with similar living environments for the Chinese undergraduates. Our data represent an important step for determining the diversity of Chinese healthy microbiota, and can be used for more large-scale studies that focus on the interactions between healthy and diseases states for young Chinese adults in the same age range.