Protective Effect of Akkermansia muciniphila against Immune-Mediated Liver Injury in a Mouse Model

Accumulating evidence indicates that gut microbiota participates in the pathogenesis and progression of liver diseases. The severity of immune-mediated liver injury is associated with different microbial communities. Akkermansia muciniphila can regulate immunologic and metabolic functions. However, little is known about its effects on gut microbiota structure and function. This study investigated the effect of A. muciniphila on immune-mediated liver injury and potential underlying mechanisms. Twenty-two C57BL/6 mice were assigned to three groups (N = 7–8 per group) and continuously administrated A. muciniphila MucT or PBS by oral gavage for 14 days. Mouse feces were collected for gut microbiota analysis on the 15th day, and acute liver injury was induced by Concanavalin A (Con A, 15 mg/kg) injection through the tail vein. Samples (blood, liver, ileum, colon) were assessed for liver injury, systemic inflammation, and intestinal barrier function. We found that oral administration of A. muciniphila decreased serum ALT and AST and alleviated liver histopathological damage induced by Con A. Serum levels of pro-inflammatory cytokines and chemokines (IL-2, IFN-γ, IL-12p40, MCP-1, MIP-1a, MIP-1b) were substantially attenuated. A. muciniphila significantly decreased hepatocellular apoptosis; Bcl-2 expression increased, but Fas and DR5 decreased. Further investigation showed that A. muciniphila enhanced expression of Occludin and Tjp-1 and inhibited CB1 receptor, which strengthened intestinal barriers and reduced systemic LPS level. Fecal 16S rRNA sequence analysis indicated that A. muciniphila increased microbial richness and diversity. The community structure of the Akk group clustered distinctly from that of mice pretreated with PBS. Relative abundance of Firmicutes increased, and Bacteroidetes abundance decreased. Correlation analysis showed that injury-related factors (IL-12p40, IFN-γ, DR5) were negatively associated with specific genera (Ruminococcaceae_UCG_009, Lachnospiraceae_UCG_001, Akkermansia), which were enriched in mice pretreated with A. muciniphila. Our results suggested that A. muciniphila MucT had beneficial effects on immune-mediated liver injury by alleviating inflammation and hepatocellular death. These effects may be driven by the protective profile of the intestinal community induced by the bacteria. The results provide a new perspective on the immune function of gut microbiota in host diseases

Prevalence and Molecular Characterization of Cyclospora cayetanensis, Henan, China

To determine prevalence of Cyclospora cayetanensis infection in Henan, China, we conducted a study of 11,554 hospital patients. Prevalence was 0.70% (95% confidence interval 0.70% ± 0.15%), with all age groups infected. Most cases were found in the summer. Minor sequence polymorphisms were observed in the 18S rRNA gene of 35 isolates characterized

Next-Generation Sequencing Applications for the Study of Fungal Pathogens

Next-generation sequencing (NGS) has become a widely used technology in biological research. NGS applications for clinical pathogen detection have become vital technologies. It is increasingly common to perform fast, accurate, and specific detection of clinical specimens using NGS. Pathogenic fungi with high virulence and drug resistance cause life-threatening clinical infections. NGS has had a significant biotechnological impact on detecting bacteria and viruses but is not equally applicable to fungi. There is a particularly urgent clinical need to use NGS to help identify fungi causing infections and prevent negative impacts. This review summarizes current research on NGS applications for fungi and offers a visual method of fungal detection. With the development of NGS and solutions for overcoming sequencing limitations, we suggest clinicians test specimens as soon as possible when encountering infections of unknown cause, suspected infections in vital organs, or rapidly progressive disease

Lactobacillus fermentum ZYL0401 Attenuates Lipopolysaccharide-Induced Hepatic TNF-α Expression and Liver Injury via an IL-10- and PGE2-EP4-Dependent Mechanism.

Lipopolysaccharide (LPS) has essential role in the pathogenesis of D-galactosamine-sensitized animal models and alcoholic liver diseases of humans, by stimulating release of pro-inflammatory mediators that cause hepatic damage and intestinal barrier impairment. Oral pretreatment of probiotics has been shown to attenuate LPS-induced hepatic injury, but it is unclear whether the effect is direct or due to improvement in the intestinal barrier. The present study tested the hypothesis that pretreatment with probiotics enables the liver to withstand directly LPS-induced hepatic injury and inflammation. In a mouse model of LPS-induced hepatic injury, the levels of hepatic tumor necrosis factor-alpha (TNF-α) and serum alanine aminotransferase (ALT) of mice with depleted intestinal commensal bacteria were not significantly different from that of the control models. Pre-feeding mice for 10 days with Lactobacillus fermentum ZYL0401 (LF41), significantly alleviated LPS-induced hepatic TNF-α expression and liver damage. After LF41 pretreatment, mice had dramatically more L.fermentum-specific DNA in the ileum, significantly higher levels of ileal cyclooxygenase (COX)-2 and interleukin 10 (IL-10) and hepatic prostaglandin E2 (PGE2). However, hepatic COX-1, COX-2, and IL-10 protein levels were not changed after the pretreatment. There were also higher hepatic IL-10 protein levels after LPS challenge in LF41-pretreated mice than in the control mice. Attenuation of hepatic TNF-α was mediated via the PGE2/E prostanoid 4 (EP4) pathway, and serum ALT levels were attenuated in an IL-10-dependent manner. A COX-2 blockade abolished the increase in hepatic PGE2 and IL-10 associated with LF41. In LF41-pretreated mice, a blockade of IL-10 caused COX-2-dependent promotion of hepatic PGE2, without affecting hepatic COX-2 levels. In LF41-pretreated mice, COX2 prevented enhancing TNF-α expression in both hepatic mononuclear cells and the ileum, and averted TNF-α-mediated increase in intestinal permeability. Together, we demonstrated that LF41 pre-feeding enabled the liver to alleviate LPS-induced hepatic TNF-α expression and injury via a PGE2-EP4- and IL-10-dependent mechanism

Multi-omics analysis of the effects of dietary changes and probiotics on diet-induced obesity

The consumption of a healthy diet is critical for maintaining and promoting human health. In the context of the rapid transformation from a high-fat diet (HFD) to a Mediterranean diet (MD) leading to major systemic changes, we explored the necessity of a transitional standard diet (TSD) between these two varied diets and the adjuvant effect of probiotics. HFD-fed mice were used for studying the changes and benefits of a dietary intervention and probiotic treatment. By measuring multiple systemic alterations such as weight (group B vs. group E, P < 0.05), liver function (AST, group C vs. group E, P < 0.001), and histopathology, we found that an MD, TSD and Bifidobacterium longum all contribute to alleviating lipid deposition and liver injury. The downregulation of IL-17 (group B vs. group E, P < 0.01) and MIP-1α (group B vs. group E, P < 0.001) also demonstrated the anti-inflammatory effects of the TSD. Moreover, we performed multi-omics analysis combined with the 16S sequencing, transcriptome and metabolome results and found that the TSD increased the abundance of the Lactobacillus genus (group C vs. group E, P < 0.01) and effectively lowered lipid accumulation and systemic inflammation. Furthermore, B. longum played an important role in the synergistic effect. The results showed that a TSD might be useful for HFD-induced obesity before drastic dietary changes, and probiotics were also beneficial

Function and evolution of two forms of SecDF homologs in Streptomyces coelicolor.

The general secretion (Sec) pathway plays a prominent role in bacterial protein export, and the accessory component SecDF has been shown to improve transportation efficiency. Inspection of Streptomyces coelicolor genome reveals the unexpected presence of two different forms of secDF homologous genes: one in fused form (secDF) and the other in separated form (secD and secF). However, the functional role of two SecDF homologs in S. coelicolor has not yet been determined. Transcriptional analysis of secDF homologs reveals that these genes are constitutively expressed. However, the transcript levels of secD and secF are much higher than that of secDF in S. coelicolor. Deletion of secDF or/and secD/secF in S. coelicolor did result in reduced secretion efficiency of Xylanase A and Amylase C, suggesting that they may have redundant functions for Sec-dependent translocation pathway. Moreover, our results also indicate that SecD/SecF plays a more prominent role than SecDF in protein translocation. Evolutionary analysis suggests that the fused and separated SecDF homologs in Streptomyces may have disparate evolutionary ancestries. SecD/SecF may be originated from vertical transmission of existing components from ancestor of Streptomyces species. However, SecDF may be derived from bacterial ancestors through horizontal gene transfer. Alternately, it is also plausible that SecDF may have arisen through additional gene duplication and fusion events. The acquisition of a second copy may confer a selective benefit to Streptomyces by enhancing protein transport capacity. Taken together, our results provide new insights into the potential biological function and evolutionary aspects of the prokaryotic SecDF complex

A new perspective on C-reactive protein in H7N9 infections

Objectives: The avian influenza H7N9 virus can cause cytokine overproduction and result in severe pneumonia and acute respiratory distress syndrome. Many studies have focused on hypercytokinemia during avian influenza infection. This study examined the association between C-reactive protein (CRP) and cytokines. Methods: The plasma cytokine and chemokine profiles of 57 H7N9 patients were investigated using a multiplex immunoassay. The CRP levels of patients with H7N9 and patients with H1N1 were also compared. Further, the association between cytokines and CRP in H7N9 infections was explored. Results: Compared with H1N1 virus, it was found that H7N9 virus induced higher expression of CRP, leading to cytokine storms. Several cytokines, including MIP-1β, MCP-1, IP-10, and IL-6, were observed to have significantly positive relationships with CRP levels, whereas IL-17A was negatively associated with CRP levels. Conclusions: These findings suggest that CRP may be used as an early indicator to identify high-risk patients, to assess disease progression, and to determine the development of hypercytokinemia

Faecal hsa-miR-7704 inhibits the growth and adhesion of Bifidobacterium longum by suppressing ProB and aggravates hepatic encephalopathy

Abstract Both gut microbiome and microRNAs (miRNAs) play a role in the development of hepatic encephalopathy (HE). However, the functional link between the microbiome and host-derived miRNAs in faeces remains poorly understood. In the present study, patients with HE had an altered gut microbiome and faecal miRNAs compared with patients with chronic hepatitis B. Transferring faeces and faecal miRNAs from patients with HE to the recipient mice aggravated thioacetamide-induced HE. Oral gavage of hsa-miR-7704, a host-derived miRNA highly enriched in faeces from patients with HE, aggravated HE in mice in a microbiome-dependent manner. Mechanistically, hsa-miR-7704 inhibited the growth and adhesion of Bifidobacterium longum by suppressing proB. B. longum and its metabolite acetate alleviated HE by inhibiting microglial activation and ammonia production. Our findings reveal the role of miRNA–microbiome axis in HE and suggest that faecal hsa-miR-7704 are potential regulators of HE progression

Butyrate Protects Mice Against Methionine–Choline-Deficient Diet-Induced Non-alcoholic Steatohepatitis by Improving Gut Barrier Function, Attenuating Inflammation and Reducing Endotoxin Levels

Butyrate exerts protective effects against non-alcoholic steatohepatitis (NASH), but the underlying mechanisms are unclear. We aimed to investigate the role of butyrate-induced gut microbiota and metabolism in NASH development. Sixty-five C57BL/6J mice were divided into four groups (n = 15–17 per group) and were fed either a methionine–choline-sufficient (MCS) diet or methionine–choline-deficient (MCD) diet with or without sodium butyrate (SoB; 0.6 g/kg body weight) supplementation for 6 weeks. Liver injury, systematic inflammation, and gut barrier function were determined. Fecal microbiome and metabolome were analyzed using 16S rRNA deep sequencing and gas chromatography-mass spectrometry (GC-MS). The results showed that butyrate alleviated the MCD diet-induced microbiome dysbiosis, as evidenced by a significantly clustered configuration separate from that of the MCD group and by the depletion of Bilophila and Rikenellaceae and enrichment of promising probiotic genera Akkermansia, Roseburia, Coprococcus, Coprobacillus, Delftia, Sutterella, and Coriobacteriaceae genera. The fecal metabolomic profile was also substantially improved by butyrate; several butyrate-responsive metabolites involved in lipid metabolism and other pathways, such as stearic acid, behenic acid, oleic acid, linoleic acid, squalene, and arachidonic acid, were identified. Correlation analysis of the interaction matrix indicated that the modified gut microbiota and fecal metabolites induced by butyrate were strongly correlated with the alleviation of hepatic injury, fibrosis progression, inflammation, and lipid metabolism and intestinal barrier dysfunction. In conclusion, our results demonstrated that butyrate exerts protective effects against NASH development, and these effects may be driven by the protective gut microbiome and metabolome induced by butyrate. This study thus provides new insights into NASH prevention