Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota.

The relationship between poor in vivo bioavailability and effective pharmacological activity are not yet fully clarified for many flavonoids. The analysis of flavonoids-induced alterations in the gut microbiota represents a promising approach to provide useful clues to elucidate the mechanism of action. Here, we investigate the effect of myricetin supplementation on high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and explore the associations with the gut microbiota through high-throughput analyses. The 12-week myricetin supplementation and fecal microbiota transplantation outcomes suggest that myricetin significantly slows the development of NAFLD. Meanwhile, the anti-NAFLD effects of myricetin are associated with the modulation of the gut microbiota composition. Myricetin reduces hepatic lipid synthesis and inflammation through modulations in fecal butyric-acid-related gut microbiota and protection of the gut barrier function. This study may facilitate the elucidation of the action mechanism of flavonoids with low bioavailability.

Diet and Nutrition for Hepatitis.

The impairment of liver function frequently causes various type of malnutrition, as the liver is one of the most important organs involved in maintaining nutritional homeostasis [...].

Gas Where It Shouldn't Be! Imaging Spectrum of Emphysematous Infections in the Abdomen and Pelvis.

OBJECTIVE. The purpose of this article is to review the spectrum, etiopathogenesis, clinical presentation, imaging features, differential diagnoses, and management of emphysematous infections of the abdomen and pelvis. CONCLUSION. Emphysematous infections are associated with high morbidity and mortality and thus need urgent medical and surgical interventions. CT is the most sensitive modality to detect gas; CT provides definitive diagnosis in most cases and can depict the extent of involvement.

CRIg+ Macrophages Prevent Gut Microbial DNA-Containing Extracellular Vesicle-Induced Tissue Inflammation and Insulin Resistance.

BACKGROUND & AIMS: Liver CRIg+ (complement receptor of the immunoglobulin superfamily) macrophages play a critical role in filtering bacteria and their products from circulation. Translocation of microbiota-derived products from an impaired gut barrier contributes to the development of obesity-associated tissue inflammation and insulin resistance. However, the critical role of CRIg+ macrophages in clearing microbiota-derived products from the bloodstream in the context of obesity is largely unknown. METHODS: We performed studies with CRIg-/-, C3-/-, cGAS-/-, and their wild-type littermate mice. The CRIg+ macrophage population and bacterial DNA abundance were examined in both mouse and human liver by either flow cytometric or immunohistochemistry analysis. Gut microbial DNA-containing extracellular vesicles (mEVs) were adoptively transferred into CRIg-/-, C3-/-, or wild-type mice, and tissue inflammation and insulin sensitivity were measured in these mice. After coculture with gut mEVs, cellular insulin responses and cGAS/STING-mediated inflammatory responses were evaluated. RESULTS: Gut mEVs can reach metabolic tissues in obesity. Liver CRIg+ macrophages efficiently clear mEVs from the bloodstream through a C3-dependent opsonization mechanism, whereas obesity elicits a marked reduction in the CRIg+ macrophage population. Depletion of CRIg+ cells results in the spread of mEVs into distant metabolic tissues, subsequently exacerbating tissue inflammation and metabolic disorders. Additionally, in vitro treatment of obese mEVs directly triggers inflammation and insulin resistance of insulin target cells. Depletion of microbial DNA blunts the pathogenic effects of intestinal EVs. Furthermore, the cGAS/STING pathway is crucial for microbial DNA-mediated inflammatory responses. CONCLUSIONS: Deficiency of CRIg+ macrophages and leakage of intestinal EVs containing microbial DNA contribute to the development of obesity-associated tissue inflammation and metabolic diseases.

Membranous Glomerulonephritis as an Uncommon Presentation of Secondary Syphilis: A Reminder on Therapeutic Decision-Making in Clinical Practice.

Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity in modern times. In this article, we chronicle an interesting case of latent syphilis masquerading as membranous glomerulonephritis, which resolved with benzathine penicillin without requiring immunosuppressive treatment. We further supplement this paper with a concise review of the relevant literature that delineates the utility of appropriate antibiotic therapy in the management of luetic membranous nephropathy. Clinicians should remain cognizant of secondary syphilis while evaluating patients for possible glomerulonephritis or those presenting with proteinuria. Additionally, patients with hepatitis B, hepatitis C, and human immunodeficiency virus infections are not infrequently coinfected with Treponema pallidum. Therefore, a high index of suspicion for systemic manifestations of syphilis such as nephrotic syndrome is warranted in the setting of a coinfection. Prompt diagnosis and treatment of syphilis may result in resolution of proteinuria, without the need for standard immunosuppressive therapy commonly used in clinical practice.

Obesity Worsens Gulf War Illness Symptom Persistence Pathology by Linking Altered Gut Microbiome Species to Long-Term Gastrointestinal, Hepatic, and Neuronal Inflammation in a Mouse Model.

Persistence of Gulf War illness (GWI) pathology among deployed veterans is a clinical challenge even after almost three decades. Recent studies show a higher prevalence of obesity and metabolic disturbances among Gulf War veterans primarily due to the existence of post-traumatic stress disorder (PTSD), chronic fatigue, sedentary lifestyle, and consumption of a high-carbohydrate/high-fat diet. We test the hypothesis that obesity from a Western-style diet alters host gut microbial species and worsens gastrointestinal and neuroinflammatory symptom persistence. We used a 5 month Western diet feeding in mice that received prior Gulf War (GW) chemical exposure to mimic the home phase obese phenotype of the deployed GW veterans. The host microbial profile in the Western diet-fed GWI mice showed a significant decrease in butyrogenic and immune health-restoring bacteria. The altered microbiome was associated with increased levels of IL6 in the serum, Claudin-2, IL6, and IL1ß in the distal intestine with concurrent inflammatory lesions in the liver and hyperinsulinemia. Microbial dysbiosis was also associated with frontal cortex levels of increased IL6 and IL1ß, activated microglia, decreased levels of brain derived neurotrophic factor (BDNF), and higher accumulation of phosphorylated Tau, an indicator of neuroinflammation-led increased risk of cognitive deficiencies. Mechanistically, serum from Western diet-fed mice with GWI significantly increased microglial activation in transformed microglial cells, increased tyrosyl radicals, and secreted IL6. Collectively, the results suggest that an existing obese phenotype in GWI worsens persistent gastrointestinal and neuronal inflammation, which may contribute to poor outcomes in restoring cognitive function and resolving fatigue, leading to the deterioration of quality of life.

Microbiota-Associated Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Cancer: A Review.

Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.

Effects of Colonization of Gnotobiotic Swiss Webster Mice with Helicobacter bilis.

Helicobacter bilis (Hb) causes hepatitis in some strains of inbred mice. The current study confirmed that Hb directly causes portal hepatitis in outbred gnotobiotic Swiss Webster (SW) mice, as we previously reported for conventional SW mice. Hbmonoassociated SW mice also developed mild enterocolitis, expanded gut-associated lymphoid tissue (GALT), and tertiary lymphoid tissue in the lower bowel. At 1 and 10 mo after infection, Hb-induced GALT hyperplasia exhibited well-organized, ectopic germinal centers with increased mononuclear cell apoptosis, MHC class II antigen presentation, and pronounced endothelial venule formation, consistent with features of tertiary lymphoid tissue. In the lower bowel, Hb induced mainly B220+ cells as well as CD4+ IL17+, CD4+ IFNγ+, and CD4+ FoxP3+ regulatory T cells and significantly increased IL10 mRNA expression. This gnotobiotic model confirmed that Hb causes portal hepatitis in outbred SW mice but stimulated GALT with an antiinflammatory bias. Because Hb had both anti- and proinflammatory effects on GALT, it should be considered a 'pathosymbiont provocateur' and merits further evaluation in mouse models of human disease.

Fungal and Parasitic Infections of the Liver.

Hepatosplenic candidiasis and other fungal infections of the liver are uncommon in healthy individuals; however, high index of suspicion is essential in immunocompromised patients with prolonged fever. Parasitic infections are protozoan or helminthic; their distribution and epidemiology are variable among different world regions. Clonorchiasis, opisthorchiasis, fascioliasis, and ascariasis are helminthic infections that commonly involve the biliary systems. Signs and symptoms of cholangitis require prompt management to relieve biliary obstruction; addition of antihelminthic agents is essential. Parasitic infections are mostly transmitted to humans by fecally contaminated food and water. Proper hand and food sanitation measures are essential in preventing disease transmission.

Cholestatic hepatitis with concomitant nephrotic syndrome due to late syphilis in an immunocompetent 32-year-old man.

A 32-year-old man was referred to our clinic for evaluation of abnormal liver function tests and concurrent proteinuria. Physical examination revealed a maculopapular rash, involving the trunk and palms, and multiple 'moth-eaten' patches of alopecia. After a prolonged diagnostic work-up a hepatitis with concomitant nephrotic syndrome due to secondary syphilis was diagnosed. Treatment with benzylpenicillin led to complete clinical recovery. Syphilis is a re-emerging infectious disease with heterogeneous clinical presentation that should be considered in the differential diagnosis of inexplicable simultaneous liver and kidney dysfunction in patients with high-risk sexual behaviour.Syphilis is a re-emerging infectious disease with heterogeneous clinical presentation that should be considered in the differential diagnosis of inexplicable simultaneous liver and kidney dysfunction in patients with high-risk sexual behaviour.

A rare cause of granulomatous hepatitis: Tularemia.

Tularemia is a zoonotic infection caused by Francisella tularensis. Tularemia has several clinical form in humans, including ulceroglandular, pneumonic, oropharyngeal, oculoglandular, and systemic (typhoidal). Tularemia may develop granulomatous and suppurative lesions, especially in the affected regional lymph nodes and various organs. Patients with hepatic involvement typically have elevated transaminase levels, hepatomegaly and rarely jaundice. Histologically, there are typically suppurative microabscesses with occasional surrounding macrophages. Rarely, hepatic granuloma can develop due to tularemia. We present a case of an 8 year-old male residing in a rural village in Turkey, who came to our hospital after having intermittent fever for four months and right upper abdominal pain for two months. Liver had a nodular appearance in liver imaging and liver biopsy were consistent with granulomatous hepatitis. The microagglutination test was positive for tularemia in the patient who was investigated for granulomatous hepatitis etiology. Symptoms and signs improved with tularemia treatment. We present a rare case of hepatic involvement of tularemia in a child. Clinicians should be suspicious of and evaluate for typhoidal tularemia in patients who present with prolonged fever and non-specific systemic symptoms, potentially with associated abdominal pain.

Mycoplasma pneumoniae-related hepatitis in children.

Mycoplasma pneumoniae (M. pneumoniae) is a small bacterium characterized by the absence of cell wall. It is a human pathogen causing upper and lower respiratory infections, both in adults and children. However, it is also considered to be implicated in the pathogenesis of several types of extra-respiratory diseases, including some gastrointestinal disorders. The liver involvement in children during or after M. pneumoniae infections is analyzed and discussed in this review. Through a systematic literature search, it is evidenced that M. pneumoniae is not infrequently associated with alteration of liver function, but rarely causes acute and severe hepatitis in children. M. pneumoniae should be considered as an unusual cause of acute hepatitis in children, whenever the most common hepatotropic viruses have been excluded. The pathogenesis of M. pneumoniae-related hepatitis is likely to be immune-mediated: both the innate and adaptive immune responses may play a fundamental role. However, the exact pathological mechanisms have to be elucidated yet. Further clinical studies are needed in order to understand the actual relevance of this microorganism in liver disease and its pathogenesis.

Epidemiology and Clinical Manifestations of Listeria monocytogenes Infection.

Listeria monocytogenes is a Gram-positive pathogenic bacterium which can be found in soil or water. Infection with the organism can develop after ingestion of contaminated food products. Small and large outbreaks of listeriosis have been described. Listeria monocytogenes can cause a number of clinical syndromes, most frequently sepsis, meningitis, and rhombencephalitis, particularly in immunocompromised hosts. The latter syndrome mimics the veterinary infection in ruminants called "circling disease". Neonatal infection can occur as a result of maternal chorioamnionitis ("early onset" sepsis) or through passage through a birth canal colonized with Listeria from the gastrointestinal tract. ("late onset" meningitis). Treatment of listeriosis is usually with a combination of ampicillin and an aminoglycoside but other regimens have been used. The mortality rate is high, reflecting the combination of an immunocompromised host and an often delayed diagnosis.

Syphilitic hepatitis: a case report and review of the literature.

BACKGROUND: Syphilis is a common disease that has been researched and focused on for many years, however, syphilitic hepatitis has not been well-recognized. We report this case of syphilitic hepatitis with intrahepatic cholestasis and liver granulomas to make a deeper impression. CASE PRESENTATION: A 47-year-old male was admitted with jaundice and rashes. The laboratory examination showed abnormal liver enzymes with significant increases in ALP and GGT but mild increases in ALT and AST. His HBV surface antigen was weakly positive, with negative HIV antibody, HCV antibody, and undetectable HBV DNA. The rapid plasma reagin test and the Treponema pallidum particle assay tests for Syphilis were both positive. Abdominal ultrasonography and magnetic resonance cholangiopancreatography revealed the normal biliary tract, liver, and spleen. The liver pathological examination showed cholangiocyte inflammation and micro-granulomas with coagulation necrosis. After 2 months of benzathine penicillin treatment, his liver enzyme decreased rapidly and remained normal after 1-year of follow-up. CONCLUSIONS: Increased liver enzymes, intrahepatic cholestasis and liver granulomas with well-response to antibiotics may provide clues for the diagnosis of syphilitic hepatitis.

Erysipelothrix Septicaemia and Hepatitis in a Colony of Humboldt Penguins (Spheniscus humboldti).

This report describes an outbreak of erysipelas in a colony of captive Humboldt penguins (Spheniscus humboldti). The only previously reported case in a related species was of an individual little blue penguin (Eudyptula minor). Five Humboldt penguins in a mixed colony displayed non-specific signs of illness, including lethargy, inappetence and regurgitation after movement for exhibit upgrading. There was no improvement after 5 days of treatment with oral enrofloxacin (10 mg/kg q24h). Four Humboldt penguins, including two that were not part of the original five displaying signs of illness, died during this outbreak and Erysipelothrix rhusiopathiae was cultured from organ samples collected post mortem. Oral clavulanic acid/amoxycillin (125 mg/kg q12h) was added to the treatment of the sick Humboldt penguins, as well as itraconazole (8.5 mg/kg q12h) and silymarin (10 mg/kg q24h) for 10 days (both per os), which resolved their clinical signs. The likely source of E. rhusiopathiae was the fish they were fed, but this could not be confirmed. Another contributing factor to the growth of E. rhusiopathiae in the exhibit pool was the increase in water temperature due to a fault in the water circulating system. The temperature of the pool water had increased to 29°C, which was rectified, and the water temperature decreased to 13°C. However, there was one further Humboldt penguin death after the decrease in water temperature. This episode suggests that E. rhusiopathiae infection should be high on the differential list of piscivorous avian species with non-specific clinical signs. A liver biopsy for bacterial culture and sensitivity may be required for definitive diagnosis.