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12 pages, 1263 KiB

Open AccessArticle

Gut Permeability and Immune-Mediated Inflammation in Heart Failure

by Maria Perticone, Simona Gigliotti, Ermal Shehaj, Raffaele Maio, Edoardo Suraci, Sofia Miceli, Francesco Andreozzi, Giovanni Matera and Francesco Perticone

Biomedicines 2024, 12(6), 1217; https://doi.org/10.3390/biomedicines12061217 - 30 May 2024

Viewed by 1014

Abstract

Heart failure (HF) is characterized by low-grade immune-mediated inflammation due to increased Toll-like receptor (TLR) expression as response to endotoxin increase and dysregulated gut barrier permeability. We investigated TLR expression and possible gut dysbiosis in HF patients compared to a control group. We [...] Read more.

Heart failure (HF) is characterized by low-grade immune-mediated inflammation due to increased Toll-like receptor (TLR) expression as response to endotoxin increase and dysregulated gut barrier permeability. We investigated TLR expression and possible gut dysbiosis in HF patients compared to a control group. We enrolled 80 Caucasian HF patients and 20 controls. Low-grade immune-mediated inflammation was evaluated by TLR expression, while gut dysbiosis by the detection of zonulin and bacterial endotoxin activity in a semi-quantitative (endotoxin activity assay [EAA]) and quantitative (limulus amebocyte lysate [LAL] test) way. Compared to controls, patients with HF showed significantly higher age and blood pressure values, worse metabolic profile and kidney function, higher inflammatory biomarkers levels, and lower levels of zonulin and endotoxin activity. When dividing failing patients in those with reduced ejection fraction (HF-rEF) and those with preserved ejection fraction (HF-pEF), HF-rEF patients showed significantly higher values of inflammatory biomarkers and TLR expression than HF-pEF patients. Gut permeability biomarkers inversely correlated with the severity of HF and positively with renal function. eGFR was retained as an independent predictor of zonulin variation in all the three groups of failing patients. Present data work to extend current knowledge about the role of gut microbiota in immune-mediated inflammation in HF. Full article

(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)

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14 pages, 2751 KiB

Open AccessArticle

Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability

by Eleni-Evangelia Koufou, Stelios F. Assimakopoulos, Pinelopi Bosgana, Anne-Lise de Lastic, Ioanna-Maria Grypari, Georgia-Andriana Georgopoulou, Stefania Antonopoulou, Athanasia Mouzaki, Helen P. Kourea, Konstantinos Thomopoulos and Periklis Davlouros

Biomedicines 2024, 12(1), 160; https://doi.org/10.3390/biomedicines12010160 - 12 Jan 2024

Viewed by 1396

Abstract

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) [...] Read more.

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (p < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF p < 0.01 for occludin, p < 0.05 for claudin-1, in HfpEF p < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, p < 0.05 for HFrEF and p < 0.001 for HFpEF; and for IL-8, p < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (p < 0.05 and p < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response. Full article

(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)

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13 pages, 1155 KiB

Open AccessArticle

The Modulation Effect of a Fermented Bee Pollen Postbiotic on Cardiovascular Microbiota and Therapeutic Perspectives

by Laura-Dorina Dinu, Florentina Gatea, Florentina Roaming Israel, Milena Lakicevic, Nebojša Dedović and Emanuel Vamanu

Biomedicines 2023, 11(10), 2712; https://doi.org/10.3390/biomedicines11102712 - 5 Oct 2023

Cited by 3 | Viewed by 2414

Abstract

Hypertension is a frequent comorbidity in patients with heart failure; therefore, blood pressure management for these patients is widely recommended in medical guidelines. Bee pollen and postbiotics that contain inactivated probiotic cells and their metabolites have emerged as promising bioactive compounds sources, and [...] Read more.

Hypertension is a frequent comorbidity in patients with heart failure; therefore, blood pressure management for these patients is widely recommended in medical guidelines. Bee pollen and postbiotics that contain inactivated probiotic cells and their metabolites have emerged as promising bioactive compounds sources, and their potential role in mitigating cardiovascular (CV) risks is currently being unveiled. Therefore, this preliminary study aimed to investigate the impact of a lactic-fermented bee pollen postbiotic (FBPP) on the CV microbiota via in vitro tests. A new isolated Lactobacillus spp. strain from the digestive tract of bees was used to ferment pollen, obtaining liquid and dried atomized caps postbiotics. The modulating effects on a CV microbiota that corresponds to the pathophysiology of hypertension were investigated using microbiological methods and qPCR and correlated with the metabolic profile. Both liquid and dried FBPPs increased the number of the beneficial Lactobacillus spp. and Bifidobacterium spp. bacteria by up to 2 log/mL, while the opportunistic pathogen E. coli, which contributes to CV pathogenesis, decreased by 3 log/mL. The short-chain fatty acid (SCFA) profile revealed a significant increase in lactic (6.386 ± 0.106 g/L) and acetic (4.284 ± 0.017 g/L) acids, both with known antihypertensive effects, and the presence of isovaleric acid, which promotes a healthy gut microbiota. Understanding the impact of the FBPP on gut microbiota could lead to innovative strategies for promoting heart health and preventing cardiovascular diseases. Full article

(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)

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13 pages, 1386 KiB

Open AccessEditor’s ChoiceArticle

Intestinal Barrier Dysfunction and Microbial Translocation in Patients with First-Diagnosed Atrial Fibrillation

by Leon Blöbaum, Marco Witkowski, Max Wegner, Stella Lammel, Philipp-Alexander Schencke, Kai Jakobs, Marianna Puccini, Daniela Reißner, Daniel Steffens, Ulf Landmesser, Ursula Rauch and Julian Friebel

Biomedicines 2023, 11(1), 176; https://doi.org/10.3390/biomedicines11010176 - 10 Jan 2023

Cited by 10 | Viewed by 2998

Abstract

Background: According to the leaky gut concept, microbial products (e.g., lipopolysaccharide, LPS) enter the circulation and mediate pro-inflammatory immunological responses. Higher plasma LPS levels have been reported in patients with various cardiovascular diseases, but not specifically during early atrial fibrillation (AF). Methods: We [...] Read more.

Background: According to the leaky gut concept, microbial products (e.g., lipopolysaccharide, LPS) enter the circulation and mediate pro-inflammatory immunological responses. Higher plasma LPS levels have been reported in patients with various cardiovascular diseases, but not specifically during early atrial fibrillation (AF). Methods: We studied data and blood samples from patients presenting with first-diagnosed AF (FDAF) (n = 80) and 20 controls. Results: Circulating biomarkers that are suggestive of mucosal inflammation (zonulin, mucosal adhesion molecule MAdCAM-1) and intestinal epithelium damage (intestinal fatty acid binding protein, IFABP) were increased in the plasma of patients with FDAF when compared to patients with chronic cardiovascular diseases but without AF. Surrogate plasma markers of increased intestinal permeability (LPS, CD14, LPS-binding protein, gut-derived LPS-neutralising IgA antibodies, EndoCAbs) were detected during early AF. A reduced ratio of IgG/IgM EndoCAbs titres indicated chronic endotoxaemia. Collagen turnover biomarkers, which corresponded to the LPS values, suggested an association of gut-derived low-grade endotoxaemia with adverse structural remodelling. The LPS concentrations were higher in FDAF patients who experienced a major adverse cardiovascular event. Conclusions: Intestinal barrier dysfunction and microbial translocation accompany FDAF. Improving gut permeability and low-grade endotoxaemia might be a potential therapeutic approach to reducing the disease progression and cardiovascular complications in FDAF. Full article

(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)

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Review

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18 pages, 650 KiB

Open AccessReview

The Role of Gut Microbiota and Its Metabolites in Patients with Heart Failure

by Krzysztof Cienkowski, Alicja Cienkowska, Karolina Kupczynska and Agata Bielecka-Dabrowa

Biomedicines 2024, 12(4), 894; https://doi.org/10.3390/biomedicines12040894 - 18 Apr 2024

Cited by 1 | Viewed by 1648

Abstract

Heart failure (HF) is a significant health concern; early detection and prevention are crucial. Recent studies suggest that the gut microbiota and its metabolites may influence HF development and risk factors. We explored this relationship by examining changes in gut microbiota composition and [...] Read more.

Heart failure (HF) is a significant health concern; early detection and prevention are crucial. Recent studies suggest that the gut microbiota and its metabolites may influence HF development and risk factors. We explored this relationship by examining changes in gut microbiota composition and metabolite levels in HF patients. HF patients often exhibit decreased alpha and beta diversity compared to controls, suggesting lower bacterial richness and community variation. Changes in specific bacterial phyla were observed, with decreases in Firmicutes (e.g., Ruminococcus) and Bacteroidetes (e.g., Prevotella) and increases in Proteobacteria (e.g., Escherichia, Shigella, and Klebsiella) and Actinobacteria. Gut-microbiota-related metabolites have been identified, potentially affecting various body systems, including the cardiovascular system. Among these are short-chain fatty acids (SCFAs), betaine, trimethylamine N-oxide (TMAO), phenylalanine, tryptophan–kynurenine, and phenylacetylgutamine (PAGIn). Although SCFAs positively affect our organisms, patients with HF have been observed to experience a decline in bacteria responsible for producing these chemical compounds. There have been indications of possible links between betaine, TMAO, phenylalanine, tryptophan–kynurenine, PAGIn, and heart failure. TMAO and phenylalanine, in particular, show promise as potential prognostic factors. However, their clinical significance has not yet been thoroughly evaluated and requires further investigation. Full article

(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)

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18 pages, 1359 KiB

Open AccessReview

Human Gut Microbiota in Heart Failure: Trying to Unmask an Emerging Organ

by Ioannis Paraskevaidis, Andrew Xanthopoulos, Elias Tsougos and Filippos Triposkiadis

Biomedicines 2023, 11(9), 2574; https://doi.org/10.3390/biomedicines11092574 - 19 Sep 2023

Cited by 5 | Viewed by 2540

Abstract

There is a bidirectional relationship between the heart and the gut. The gut microbiota, the community of gut micro-organisms themselves, is an excellent gut-homeostasis keeper since it controls the growth of potentially harmful bacteria and protects the microbiota environment. There is evidence suggesting [...] Read more.

There is a bidirectional relationship between the heart and the gut. The gut microbiota, the community of gut micro-organisms themselves, is an excellent gut-homeostasis keeper since it controls the growth of potentially harmful bacteria and protects the microbiota environment. There is evidence suggesting that a diet rich in fatty acids can be metabolized and converted by gut microbiota and hepatic enzymes to trimethyl-amine N-oxide (TMAO), a product that is associated with atherogenesis, platelet dysfunction, thrombotic events, coronary artery disease, stroke, heart failure (HF), and, ultimately, death. HF, by inducing gut ischemia, congestion, and, consequently, gut barrier dysfunction, promotes the intestinal leaking of micro-organisms and their products, facilitating their entrance into circulation and thus stimulating a low-grade inflammation associated with an immune response. Drugs used for HF may alter the gut microbiota, and, conversely, gut microbiota may modify the pharmacokinetic properties of the drugs. The modification of lifestyle based mainly on exercise and a Mediterranean diet, along with the use of pre- or probiotics, may be beneficial for the gut microbiota environment. The potential role of gut microbiota in HF development and progression is the subject of this review. Full article

(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)

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22 pages, 1905 KiB

Open AccessReview

Recent Advances in Microbiota-Associated Metabolites in Heart Failure

by Sepiso K. Masenga, Joreen P. Povia, Propheria C. Lwiindi and Annet Kirabo

Biomedicines 2023, 11(8), 2313; https://doi.org/10.3390/biomedicines11082313 - 21 Aug 2023

Cited by 10 | Viewed by 3579

Abstract

Heart failure is a risk factor for adverse events such as sudden cardiac arrest, liver and kidney failure and death. The gut microbiota and its metabolites are directly linked to the pathogenesis of heart failure. As emerging studies have increased in the literature [...] Read more.

Heart failure is a risk factor for adverse events such as sudden cardiac arrest, liver and kidney failure and death. The gut microbiota and its metabolites are directly linked to the pathogenesis of heart failure. As emerging studies have increased in the literature on the role of specific gut microbiota metabolites in heart failure development, this review highlights and summarizes the current evidence and underlying mechanisms associated with the pathogenesis of heart failure. We found that gut microbiota-derived metabolites such as short chain fatty acids, bile acids, branched-chain amino acids, tryptophan and indole derivatives as well as trimethylamine-derived metabolite, trimethylamine N-oxide, play critical roles in promoting heart failure through various mechanisms. Mainly, they modulate complex signaling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells, Bcl-2 interacting protein 3, NLR Family Pyrin Domain Containing inflammasome, and Protein kinase RNA-like endoplasmic reticulum kinase. We have also highlighted the beneficial role of other gut metabolites in heart failure and other cardiovascular and metabolic diseases. Full article

(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)

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19 pages, 1310 KiB

Open AccessEditor’s ChoiceReview

The Interaction of Gut Microbiota and Heart Failure with Preserved Ejection Fraction: From Mechanism to Potential Therapies

by Wei Yu, Yufeng Jiang, Hui Xu and Yafeng Zhou

Biomedicines 2023, 11(2), 442; https://doi.org/10.3390/biomedicines11020442 - 2 Feb 2023

Cited by 9 | Viewed by 3653

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a disease for which there is no definite and effective treatment, and the number of patients is more than 50% of heart failure (HF) patients. Gut microbiota (GMB) is a general term for a group [...] Read more.

Heart failure with preserved ejection fraction (HFpEF) is a disease for which there is no definite and effective treatment, and the number of patients is more than 50% of heart failure (HF) patients. Gut microbiota (GMB) is a general term for a group of microbiota living in humans’ intestinal tracts, which has been proved to be related to cardiovascular diseases, including HFpEF. In HFpEF patients, the composition of GMB is significantly changed, and there has been a tendency toward dysbacteriosis. Metabolites of GMB, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs) and bile acids (BAs) mediate various pathophysiological mechanisms of HFpEF. GMB is a crucial influential factor in inflammation, which is considered to be one of the main causes of HFpEF. The role of GMB in its important comorbidity—metabolic syndrome—also mediates HFpEF. Moreover, HF would aggravate intestinal barrier impairment and microbial translocation, further promoting the disease progression. In view of these mechanisms, drugs targeting GMB may be one of the effective ways to treat HFpEF. This review focuses on the interaction of GMB and HFpEF and analyzes potential therapies. Full article

(This article belongs to the Special Issue Recent Advances in Gut Microbiome and Heart Failure)

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