Rifaximin Alleviates Endotoxemia with Decreased Serum Levels of Soluble CD163 and Mannose Receptor and Partial Modification of Gut Microbiota in Cirrhotic Patients

Rifaximin is a poorly absorbable antibiotic against hepatic encephalopathy (HE). This observational study aimed to elucidate the effect of rifaximin on intestinal permeability and gut microbiota in patients with decompensated cirrhosis. Thirty patients with decompensated cirrhosis were assessed by ammonia level, neuropsychological testing, endotoxin activity (EA), and serum proinflammatory cytokines at baseline and after four weeks of rifaximin treatment (1200 mg/day). Intestinal permeability was indicated by serum soluble CD163 (sCD163), mannose receptor (sMR), and zonulin levels. To evaluate the gut microbiome, 16S ribosomal RNA gene sequencing was applied. Rifaximin ameliorated hyperammonemia and cognitive dysfunction, although it did not change the serum proinflammatory cytokine levels. It decreased EA levels as well as serum levels of sCD163 and sMR, but not zonulin, and both decreases in sCD163 and sMR showed positive correlations with EA decrease (ΔsCD163: Correlation coefficient (R) = 0.680, p = 0.023; ΔsMR: R = 0.613, p = 0.014, vs. ΔEA). Gut microbial analysis revealed that the richness and complexity of species were unchanged while the abundance of the Streptococcus genus was reduced after treatment with rifaximin. Collectively, rifaximin alleviated HE and endotoxemia with improved intestinal hyperpermeability in patients with decompensated cirrhosis, and this effect is partially involved in a gut microbial change.

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No effect of rifaximin on soluble CD163, mannose receptor or type III and IV neoepitope collagen markers in decompensated cirrhosis: Results from a randomized, placebo controlled trial

PLoS ONE ◽

10.1371/journal.pone.0203200 ◽

2018 ◽

Vol 13 (9) ◽

pp. e0203200 ◽

Cited By ~ 4

Author(s):

Nina Kimer ◽

Natasja Stæhr Gudmann ◽

Julie Steen Pedersen ◽

Søren Møller ◽

Mette Juul Nielsen ◽

...

Keyword(s):

Controlled Trial ◽

Mannose Receptor ◽

Decompensated Cirrhosis ◽

Type Iii ◽

Soluble Cd163 ◽

Collagen Markers

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Prevention of Gestational Diabetes Mellitus (GDM) and Probiotics: Mechanism of Action: A Review

Current Diabetes Reviews ◽

10.2174/1573399815666190712193828 ◽

2020 ◽

Vol 16 (6) ◽

pp. 538-545 ◽

Cited By ~ 2

Author(s):

Aziz Homayouni ◽

Nahal Bagheri ◽

Sakineh Mohammad-Alizadeh-Charandabi ◽

Neda Kashani ◽

Noshin Mobaraki-Asl ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gut Microbiota ◽

Gestational Diabetes Mellitus ◽

Intestinal Permeability ◽

Mechanism Of Action ◽

Economic Cost ◽

Slight Reduction ◽

Future Health ◽

Keywords Probiotics

Background: : Gestational Diabetes Mellitus (GDM) is a health problem that is increasing around the world. Introduction:: Prevention of GDM, rather than treatment, could have several benefits in terms of both health and economic cost. Even a slight reduction in maternal glucose in non-diabetic women, particularly in women at high risk for GDM, may have significant benefits for pregnancy results and the future health of off-springs. Probiotics are a relatively new intervention, which are assessed by mothers’ metabolism, and can reduce blood sugar levels, prevent gestational diabetes and reduce the maternal and fetal complications resulting from it. The aim of this study was to review the studies on the prevention of gestational diabetes and assess the potential beneficial effects of probiotics on gestational diabetes and their possible mechanism of action. Method:: Articles compiled through clinical trials indexed in PubMed, Science Direct, Cochran, and Medlib between 2000 and 2017, with the keywords probiotics, prevention, and gestational diabetes mellitus were selected. Result:: Considering the potential of probiotics in the modulation of gut microbiota, naturalization increases intestinal permeability, regulation of pro-inflammatory mediators’ secretion and thereby controlling local and systemic inflammation results in decreasing intestinal permeability, enhancing the immune system. It likely has the ability to prevent or control diabetes during pregnancy although confirmatory studies are still needed. Conclusion:: Experimental and clinical evidence support the supposition that the modulation of the gut microbiota via probiotic microorganisms could be effective in the prevention of gestational diabetes mellitus.

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Detection of Dysbiosis and Increased Intestinal Permeability in Brazilian Patients with Relapsing–Remitting Multiple Sclerosis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094621 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4621

Author(s):

Felipe Papa Pellizoni ◽

Aline Zazeri Leite ◽

Nathália de Campos Rodrigues ◽

Marcelo Jordão Ubaiz ◽

Marina Ignácio Gonzaga ◽

...

Keyword(s):

Multiple Sclerosis ◽

Gut Microbiota ◽

Intestinal Permeability ◽

Dietary Habits ◽

Dietary Interventions ◽

Chi Square ◽

16S Sequencing ◽

Intestinal Dysbiosis ◽

Relapsing Remitting ◽

Relapsing Remitting Multiple Sclerosis

Dysbiosis, associated with barrier disruption and altered gut–brain communications, has been associated with multiple sclerosis (MS). In this study, we evaluated the gut microbiota in relapsing–remitting patients (RRMS) receiving disease-modifying therapies (DMTs) and correlated these data with diet, cytokines levels, and zonulin concentrations. Stool samples were used for 16S sequencing and real-time PCR. Serum was used for cytokine determination by flow cytometry, and zonulin quantification by ELISA. Pearson’s chi-square, Mann–Whitney, and Spearman’s correlation were used for statistical analyses. We detected differences in dietary habits, as well as in the gut microbiota in RRMS patients, with predominance of Akkermansia muciniphila and Bacteroides vulgatus and decreased Bifidobacterium. Interleukin-6 concentrations were decreased in treated patients, and we detected an increased intestinal permeability in RRMS patients when compared with controls. We conclude that diet plays an important role in the composition of the gut microbiota, and intestinal dysbiosis, detected in RRMS patients could be involved in increased intestinal permeability and affect the clinical response to DTMs. The future goal is to predict therapeutic responses based on individual microbiome analyses (personalized medicine) and propose dietary interventions and the use of probiotics or other microbiota modulators as adjuvant therapy to enhance the therapeutic efficacy of DMTs.

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Real-World Experience of the One-Year Efficacy of Rifaximin Add-On to Lactulose Is Superior to Lactulose Alone in Patients with Cirrhosis Complicated with Recurrent Hepatic Encephalopathy in Taiwan

Journal of Personalized Medicine ◽

10.3390/jpm11060478 ◽

2021 ◽

Vol 11 (6) ◽

pp. 478

Author(s):

Ching Chang ◽

Chien-Hao Huang ◽

Hsiao-Jung Tseng ◽

Fang-Chen Yang ◽

Rong-Nan Chien

Keyword(s):

Hepatic Encephalopathy ◽

Real World ◽

Ammonia Level ◽

Decompensated Cirrhosis ◽

Control Group ◽

Multivariable Logistic Regression Model ◽

Before And After ◽

One Year ◽

The One ◽

Serum Ammonia

Background: Hepatic encephalopathy (HE), a neuropsychiatric complication of decompensated cirrhosis, is associated with high mortality and high risk of recurrence. Rifaximin add-on to lactulose for 3 to 6 months is recommended for the prevention of recurrent episodes of HE after the second episode. However, whether the combination for more than 6 months is superior to lactulose alone in the maintenance of HE remission is less evident. Therefore, the aim of this study is to evaluate the one-year efficacy of rifaximin add-on to lactulose for the maintenance of HE remission in Taiwan. Methods: We conducted a real-world single-center retrospective cohort study to compare the long-term efficacy of rifaximin add-on to lactulose (group R + L) versus lactulose alone (group L, control group). Furthermore, the treatment efficacy before and after rifaximin add-on to lactulose was also analyzed. The primary endpoint of our study was time to first HE recurrence (Conn score ≥ 2). All patients were followed up every three months until death, and censored at one year if still alive. Results and Conclusions: 12 patients were enrolled in group R + L. Another 31 patients were stratified into group L. Sex, comorbidity, ammonia level, and ascites grade were matched while age, HE grade, and model for end-stage liver disease (MELD) score were adjusted in the multivariable logistic regression model. Compared with group L, significant improvement in the maintenance of HE remission and decreased episodes and days of HE-related hospitalizations were demonstrated in group R + L. The serum ammonia levels were significantly lower at the 3rd and 6th month in group 1. Concerning changes before and after rifaximin add-on in group R + L, mini-mental status examination (MMSE), episodes of hospitalization, and variceal bleeding also improved at 6 and 12 months. Days of hospitalization, serum ammonia levels also improved at 6th month. Except for concern over price, no patients discontinued rifaximin due to adverse events or complications. The above results provide evidence for the one-year use of rifaximin add-on to lactulose in reducing HE recurrence and HE-related hospitalization for patients with decompensated cirrhosis.

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Effect of Lacticaseibacillus paracasei Strain Shirota on Improvement in Depressive Symptoms, and Its Association with Abundance of Actinobacteria in Gut Microbiota

Microorganisms ◽

10.3390/microorganisms9051026 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1026

Author(s):

Machiko Otaka ◽

Hiroko Kikuchi-Hayakawa ◽

Jun Ogura ◽

Hiroshi Ishikawa ◽

Yukihito Yomogida ◽

...

Keyword(s):

Depressive Symptoms ◽

Gut Microbiota ◽

Intestinal Permeability ◽

Rating Scale ◽

Psychiatric Symptoms ◽

Daily Intake ◽

Probiotic Strain ◽

Major Depressive ◽

Colony Forming Units ◽

And Biological Markers

We previously reported lower counts of lactobacilli and Bifidobacterium in the gut microbiota of patients with major depressive disorder (MDD), compared with healthy controls. This prompted us to investigate the possible efficacy of a probiotic strain, Lacticaseibacillus paracasei strain Shirota (LcS; basonym, Lactobacillus casei strain Shirota; daily intake of 8.0 × 1010 colony-forming units), in alleviating depressive symptoms. A single-arm trial was conducted on 18 eligible patients with MDD or bipolar disorder (BD) (14 females and 4 males; 15 MDD and 3 BD), assessing changes in psychiatric symptoms, the gut microbiota, and biological markers for intestinal permeability and inflammation, over a 12-week intervention period. Depression severity, evaluated by the Hamilton Depression Rating Scale, was significantly alleviated after LcS treatment. The intervention-associated reduction of depressive symptoms was associated with the gut microbiota, and more pronounced when Bifidobacterium and the Atopobium clusters of the Actinobacteria phylum were maintained at higher counts. No significant changes were observed in the intestinal permeability or inflammation markers. Although it was difficult to estimate the extent of the effect of LcS treatment alone, the results indicated that it was beneficial to alleviate depressive symptoms, partly through its association with abundance of Actinobacteria in the gut microbiota.

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Continuous elevation of procalcitonin in cirrhosis combined with hepatic carcinoma: a case report

BMC Infectious Diseases ◽

10.1186/s12879-020-05684-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Juan Lu ◽

Chun-lei Chen ◽

Jian-di Jin ◽

Jun Chen ◽

Cheng-bo Yu

Keyword(s):

Liver Disease ◽

Bacterial Infection ◽

Severe Infection ◽

Serum Levels ◽

Decompensated Cirrhosis ◽

Hepatic Carcinoma ◽

Multiple Loci ◽

Before And After ◽

Severe Cirrhosis ◽

End Stage

Abstract Background Serum levels of procalcitonin (PCT) are considered a useful biomarker for the diagnosis of bacterial infection or inflammation. There are few reports of high PCT levels in end-stage liver disease regardless of bacterial infection. Here, we present a case of extremely high PCT levels (> 100 ng/mL) in a patient with severe cirrhosis combined with hepatic carcinoma. Case presentation A 65-year-old man developed end-stage cirrhosis with hepatic carcinoma. Radiographic imaging showed a massive hepatocellular carcinoma with multiple loci lack of indications of resection. Hence, transcatheter hepatic arterial chemoembolization was performed three times over a period of 4 months. Before and after interventional therapies, the biochemistry laboratory results were only slightly abnormal except for persistently high PCT concentrations (> 100 ng/mL), irrespective of the evidence for bacterial infection or sepsis. Conclusions This case suggests that continuously high levels of PCT (> 100 ng/mL) may be present in advanced liver disease, particularly in complex situations such as decompensated cirrhosis and liver cancer, in the absence of severe infection or sepsis. This knowledge could expand the significance of PCT in liver disease.

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Intestinal Permeability Is a Mechanical Rheostat in the Pathogenesis of Liver Cirrhosis

International Journal of Molecular Sciences ◽

10.3390/ijms22136921 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6921

Author(s):

Norihisa Nishimura ◽

Kosuke Kaji ◽

Koh Kitagawa ◽

Yasuhiko Sawada ◽

Masanori Furukawa ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Intestinal Permeability ◽

Proinflammatory Cytokines ◽

Liver Diseases ◽

Pathogenic Bacteria ◽

Necrosis Factor Alpha ◽

Cytokines And Chemokines ◽

Liver Disease Progression ◽

Cirrhotic Patients

Recent studies have suggested that an alteration in the gut microbiota and their products, particularly endotoxins derived from Gram-negative bacteria, may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, which means higher translocation of bacteria and their products and components, including endotoxins, the so-called “leaky gut”. Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases, including alcoholic liver disease and nonalcoholic liver disease. A decrease in commensal nonpathogenic bacteria including Ruminococaceae and Lactobacillus and an overgrowth of pathogenic bacteria such as Bacteroidaceae and Enterobacteriaceae are observed in cirrhotic patients. The decreased diversity of the gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of post-transplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via Toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is a major receptor activated by the binding of endotoxins in macrophages, and its downstream signal induces proinflammatory cytokines. The expression of TLR4 is also observed in nonimmune cells in the liver, such as hepatic stellate cells, which play a crucial role in the progression of liver fibrosis that develops into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression. In this review, we summarize the findings for the role of gut-derived endotoxemia underlying the progression of liver pathogenesis.

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OP0035 ASSESSMENT OF THE INTESTINAL PERMEABILITY IN PATIENTS WITH RHEUMATOID ARTHRITIS USING COLONIC TISSUES AND SERA

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2642 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 19.2-19

Author(s):

R. Audo ◽

P. Sanchez ◽

J. Mielle ◽

L. Macia ◽

B. Rivière ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gut Microbiota ◽

Intestinal Permeability ◽

Systemic Inflammation ◽

Inflammatory Diseases ◽

Staining Intensity ◽

Serum Markers ◽

Before And After ◽

Colonic Biopsies ◽

Junction Proteins

Background:Patients with rheumatoid arthritis (RA) have an altered gut microbiota (dysbiosis) (1-3). This microbiota interacts with intestinal epithelium which can lead to an increased intestinal permeability, responsible for the passage of antigens and inflammatory molecules, and can therefore promote systemic inflammation. Gut microbiota tends to normalize with disease control (2), suggesting that systemic inflammation may directly influence the composition of microbiota and the gut barrier. It was shown in many inflammatory diseases that intestinal permeability is impaired, but to date there is very little data in RA.Objectives:In the present study, we evaluate the intestinal permeability in RA patients by analyzing tight junctions in colonic biopsies and serum markers.Methods:Colonic biopsies from 20 RA patients who underwent coloscopy for screening with normal histology were compared with those from 20 age and sex matched controls. ZO-1, occludin and claudin 2 junction proteins were evaluated by immunohistochemistry. The staining intensity was assessed by two blinded independent readers. The serum concentrations of LPS-binding protein (LBP), CD14s and zonulin were evaluated by ELISA in 25 patients naive of DMARDs, 41 patients before and after introduction of a DMARDs and 21 controls. Elevated zonulin in serum indicates an increase in intestinal permeability while LBP and CD14s indicate bacterial translocation.Results:ZO-1 expression was significantly lower in biopsies from patients with RA than controls (mean score ± SD of 1.6 ± 0.56 vs 2.0 ± 0.43; p = 0.01). Age, sex, disease duration and immunological status did not significantly influence the expression of colonic junction proteins. LBP and CD14s were higher in serum from RA patients naive of DMARDs than controls (p = 0.002 and p = 0.003). LBP, CD14s and zonulin levels significantly correlated with DAS28 (r = 0.61, p = 0.005; r = 0.51, p = 0.030 and r = 0.46, p = 0.049, respectively). After treatment, unlike non-responders, LBP and CD14s were significantly reduced in DMARD responders and variations in LBP and CD14s significantly correlated with changes in DAS28 (r = 0.46, p = 0.002 and r = 0, 33 and p = 0.030, respectively).Conclusion:This work is one of the first to explore intestinal permeability in RA and to show altered tight junction in colonic tissue from RA. This increased intestinal permeability appears to be related to the systemic inflammation. Improving the gut microbiota through food or probiotics could enhance the effect of treatments by limiting this amplification loop of inflammation.References:[1]Horta-Baas G, Romero-Figueroa MDS, Montiel-Jarquin AJ, Pizano-Zarate ML, Garcia-Mena J, Ramirez-Duran N. Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis. J Immunol Res. 2017;2017:4835189.[2]Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895-905.[3]Maeda Y, Kurakawa T, Umemoto E, Motooka D, Ito Y, Gotoh K, et al. Dysbiosis Contributes to Arthritis Development via Activation of Autoreactive T Cells in the Intestine. Arthritis Rheumatol. 2016;68(11):2646-61.Disclosure of Interests:Rachel Audo: None declared, Pauline Sanchez: None declared, Julie Mielle: None declared, Laurence Macia: None declared, Benjamin Rivière: None declared, Cédric Lukas: None declared, Bernard Combe: None declared, Jacques Morel: None declared, Claire Daien Speakers bureau: Pfizer roche chugai fresenius BMS msd Novartis galapagos, Consultant of: Abivax abbbvie BMS roche chugai, Grant/research support from: Pfizer, roche-chugai, fresenius, msd

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Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis

Scientific Reports ◽

10.1038/s41598-021-94090-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alice Wang ◽

Nishi Karunasinghe ◽

Lindsay D. Plank ◽

Shuotun Zhu ◽

Sue Osborne ◽

...

Keyword(s):

Androgen Deprivation Therapy ◽

Longitudinal Analysis ◽

Serum Levels ◽

Androgen Deprivation ◽

Mineral Density ◽

Cross Sectional ◽

Prognostic Features ◽

Increased Risk ◽

Positive Correlations ◽

Dickkopf 1

AbstractAndrogen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers—sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (− 10.06%, p = 0.0057), former-ADT (− 12.77%, p = 0.0239), and in PCa controls group (− 16.73, p = 0.0022); and OPG levels in chronic ADT (− 8.28%, p = 0.003) and PCa controls group (− 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

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Nuciferine improves high-fat diet-induced obesity by reducing intestinal permeability through increasing autophagy and remodeling the gut microbiota

Food & Function ◽

10.1039/d1fo00367d ◽

2021 ◽

Author(s):

Zhen Shi ◽

Zhiyuan Fang ◽

Xinxing Gao ◽

Hao Yu ◽

Yiwei Zhu ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Permeability ◽

High Fat Diet ◽

Metabolic Diseases ◽

High Fat ◽

Diet Induced Obesity ◽

Medicinal Value

Nuciferine (NF) has received extensive attention for its medicinal value in the treatment of metabolic diseases, such as obesity, but the effects of NF on obesity-related intestinal permeability, autophagy and...

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