Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

Juanola, Oriol; Ferrusquía‐Acosta, José; Garcı́a-Villalba, Rocío; Zapater, Pedro; Magaz, Marta; Marín, Alicia; Olivas, Pol; Baiges, Anna; Bellot, Pablo; Turón, Fanny; Hernández‐Gea, Virginia; González‐Navajas, José M.; Tomás-Barberán, Francisco A.; García‐Pagán, Juan Carlos; Francés, Rubén

doi:10.1096/fj.201901327r

Cited by 84 publications

(82 citation statements)

References 51 publications

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“…Accumulating studies show that hypertension is strongly associated with enteric dysbacteriosis, which is accompanying with reduction in butyrate-producing bacteria [92,[126][127][128]. Interestingly, circulating levels of butyrate are inversely related to portal hypertension [129], and butyrate could directly suppress Ang II-induced hypertension through inhibiting renal (pro)renin receptor (PRR)-mediated renin release [130]. However, the fundamental mechanisms underlying butyrate roles in regulating atherosclerosis and hypertension are not known.…”

Section: Butyrate and Butyrylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Metabolic dysfunction is a fundamental core mechanism underlying CVDs. Previous studies generally focused on the roles of long-chain fatty acids (LCFAs) in CVDs. However, a growing body of study has implied that short-chain fatty acids (SCFAs: namely propionate, malonate, butyrate, 2-hydroxyisobutyrate (2-HIBA), β-hydroxybutyrate, crotonate, succinate, and glutarate) and their cognate acylations (propionylation, malonylation, butyrylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation, crotonylation, succinylation, and glutarylation) participate in CVDs. Here, we attempt to provide an overview landscape of the metabolic pattern of SCFAs in CVDs. Especially, we would focus on the SCFAs and newly identified acylations and their roles in CVDs, including atherosclerosis, hypertension, and heart failure. Clinical Science (2020) 134 657-676 https://doi.org/10.1042/CS20200128 cofactors in certain protein acylations, such as propionylation [14], malonylation [15], butyrylation [14], 2-hydroxyisobutyrylation [16], β-hydroxybutyrylation [17], crotonylation [18], succinylation [19], and glutarylation [20]. These discoveries give us a deeper understanding of PTM. Among PTMs, protein acetylation is the earliest discovered and most studied. Similar to protein acetylation, various studies have shown that these newly discovered PTMs are also involved in physiological and pathophysiological processes, including cardiovascular homeostasis.Here in this review, we will summarize SCFAs, protein acylations, and their emerging roles in CVDs, including atherosclerosis, hypertension, and heart failure. The metabolic pattern and FAs in CVDsThe heart is an 'omnivore' , using FAs, glucose, lactate, ketone bodies, and amino acids as metabolic substrates [5,6]. The substrates utilized by the embryonic heart are significantly different from those used by the adult heart. The embryonic heart depends primarily on glycolysis as well as lactate oxidation to produce energy [21]. The newborn and adult heart shift toward the remarkable utilization of FAs to meet cardiac energy demand [5,9]. In failing hearts, a decrease in FA oxidation and an increase in glycolysis are critically involved in cardiac dysfunction [22]. As thus, the metabolic pattern is essential for maintaining cardiac and vascular functions.Diabetes, hypertension, and obesity contribute to heart failure syndrome. Accumulating evidence suggests that hypertension, ischemic hearts, and heart failure induce a shift in substrate toward the remarkable utilization of glucose to generate energy. Despite this shift, the FA oxidation remains to make much energy for the diseased heart [23]. Since FAs are the predominant substrates for cardiomyocytes, alterations in FA metabolism have been implicated as causal in cardiac diseases. FAs within cells and in the circulation are critically involved in cardiometabolic diseases. CVDs are closely associated with lifestyle and metabolic status, which affect circul...

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Section: Butyrate and Butyrylationmentioning

confidence: 99%

Short-chain fatty acid, acylation and cardiovascular diseases

2020

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“…There is a further reduction of SCFAs in cirrhosis with HE. Butyrate has a negative correlation with inflammatory markers and serum endotoxin (Juanola et al, 2019). SCFAs bind the G-protein-coupled receptor 43 (GPR43) to promote the regression of inflammation (Maslowski et al, 2009).…”

Section: Short-chain Fatty Acidsmentioning

confidence: 99%

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

Chen

Ruan

et al. 2021

Front. Cell. Infect. Microbiol.

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Hepatic encephalopathy (HE) is a neurological disorder that occurs in patients with liver insufficiency. However, its pathogenesis has not been fully elucidated. Pharmacotherapy is the main therapeutic option for HE. It targets the pathogenesis of HE by reducing ammonia levels, improving neurotransmitter signal transduction, and modulating intestinal microbiota. Compared to healthy individuals, the intestinal microbiota of patients with liver disease is significantly different and is associated with the occurrence of HE. Moreover, intestinal microbiota is closely associated with multiple links in the pathogenesis of HE, including the theory of ammonia intoxication, bile acid circulation, GABA-ergic tone hypothesis, and neuroinflammation, which contribute to cognitive and motor disorders in patients. Restoring the homeostasis of intestinal bacteria or providing specific probiotics has significant effects on neurological disorders in HE. Therefore, this review aims at elucidating the potential microbial mechanisms and metabolic effects in the progression of HE through the gut–brain axis and its potential role as a therapeutic target in HE.

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“…Acetic acid and propionic acid are metabolized and used in the liver and muscle. Juanola et al 25 . reported that short chain fatty acids (mainly butyric acid) are inversely correlated with the model for end‐stage liver disease score and were reduced in patients with a history of ascites, hepatic encephalopathy, or spontaneous bacterial peritonitis.…”

Section: Discussionmentioning

confidence: 99%

The relationship between oral‐origin bacteria in the fecal microbiome and albumin–bilirubin grade in patients with hepatitis C

Yamamoto

Honda

Ito

et al. 2020

J of Gastro and Hepatol

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Background Bacteria of oral origin (BO) in the gut are associated with prognosis in patients with cirrhosis. The Greengenes database (gg_13_8) is widely used in microbiome analysis, but the expanded Human Oral Microbiome Database (eHOMD), a specialized database for BO, can add more detailed information. We used each database to evaluate the relationship between the albumin–bilirubin grade (ALBI) and the microbiome in patients with hepatitis C. Methods Eighty patients were classified into the low ALBI group (LA; n = 34) or high ALBI group (HA; n = 46). Isolated DNA from stool was amplified to target the V3–4 regions of 16S rRNA. The microbiomes of the two groups were compared using gg_13_8 or eHOMD. We evaluated the associations between microbiomes and prognoses using Cox proportional hazards models. Results At the genus level, the two groups differed significantly regarding 6 (gg_13_8) and 7 (eHOMD) types of bacteria. All types except Akkermansia are classified as BO. Both databases showed an increase in Streptococcus and Veillonella. eHOMD showed a decrease in Fusobacterium and an increase in Fretibacterium; both produce various types of short‐chain fatty acids. At the species level, the two groups demonstrated significant differences in 2 (gg_13_8) and 6 (eHOMD) bacterial types. Selenomonas noxia and Streptococcus salivarius were related to poor prognosis in univariate analysis. Conclusion The HA group demonstrated increased BO, most of which produce lactic acid or acetic acid. The correlation between the microbiome and metabolism might be related to prognosis. eHOMD was a useful database for analyzing BO.

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Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis

Cited by 84 publications

References 51 publications

Short-chain fatty acid, acylation and cardiovascular diseases

Short-chain fatty acid, acylation and cardiovascular diseases

The Role of Intestinal Bacteria and Gut–Brain Axis in Hepatic Encephalopathy

The relationship between oral‐origin bacteria in the fecal microbiome and albumin–bilirubin grade in patients with hepatitis C

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