Deoxycholic acid transformations catalyzed by selected filamentous fungi

Kollerov, Vyacheslav; Lobastova, Tatyana G.; Monti, Daniela; Deshcherevskaya, N.O.; Ferrandi, Erica Elisa; Fronza, Giovanni; Riva, Sergio; Donova, Marina V.

doi:10.1016/j.steroids.2015.12.015

Cited by 21 publications

(23 citation statements)

References 32 publications

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“…It was shown to improve insulin sensitivity in a murine model of diabetes,39 and there is evidence to indicate that this effect could also occur in patients with the metabolic syndrome 40. Most of the correlations we found between gut bacteria and liver tests were with bilirubinaemia, highlighting the strong link between cholestasis and bile acids on the one hand and gut microbiota on the other, as recently reported by Torres et al 19 It should be emphasised in this respect that bacteria and fungi are able to metabolise bile acids 41. Almost all patients with PSC included in this study were on UDCA treatment (94%), which may have influenced our results.…”

Section: Discussionsupporting

confidence: 71%

Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

Lemoinne¹,

Kemgang²,

Belkacem³

et al. 2019

Gut

150

134

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ObjectivePatients with primary sclerosing cholangitis (PSC) were previously shown to display a bacterial gut dysbiosis but fungal microbiota has never been examined in these patients. The aim of this study was to assess the fungal gut microbiota in patients with PSC.DesignWe analysed the faecal microbiota of patients with PSC and concomitant IBD (n=27), patients with PSC and no IBD (n=22), patients with IBD and no PSC (n=33) and healthy subjects (n=30). Bacterial and fungal composition of the faecal microbiota was determined using 16S and ITS2 sequencing, respectively.ResultsWe found that patients with PSC harboured bacterial dysbiosis characterised by a decreased biodiversity, an altered composition and a decreased correlation network density. These alterations of the microbiota were associated with PSC, independently of IBD status. For the first time, we showed that patients with PSC displayed a fungal gut dysbiosis, characterised by a relative increase in biodiversity and an altered composition. Notably, we observed an increased proportion of Exophiala and a decreased proportion of Saccharomyces cerevisiae. Compared with patients with IBD and healthy subjects, the gut microbiota of patients with PSC exhibited a strong disruption in bacteria-fungi correlation network, suggesting an alteration in the interkingdom crosstalk.ConclusionThis study demonstrates that bacteria and fungi contribute to gut dysbiosis in PSC.

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Section: Discussionsupporting

confidence: 71%

Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

Lemoinne¹,

Kemgang²,

Belkacem³

et al. 2019

Gut

150

134

View full text Add to dashboard Cite

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“…The 12aBAs in this study are as follows: CA, UCA, DCA, TCA, TDCA, GCA, GDCA, 7oDCA and 12oLCA. Among these BAs, 12oLCA possesses an oxo group at position 12 on the steroid ring and is not a genuine 12aBA, but we included 12oLCA in the 12aBA family in the present study because this molecule can originate from one of the 12aBAs, DCA (19). Blood aminotransferase activities, glucose, and insulin.…”

Section: Methodsmentioning

confidence: 99%

Alteration of Bile Acid Metabolism by a High-Fat Diet Is Associated with Plasma Transaminase Activities and Glucose Intolerance in Rats

Yoshitsugu

Kikuchi

Iwaya

et al. 2019

Journal of Nutritional Science and Vitaminology

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Ingestion of a high-fat (HF) diet is known to enhance bile acid (BA) secretion, but precise information about the BA molecular species is lacking, especially information on the conjugated BAs in enterohepatic circulation. As cholesterol is the precursor of BAs, we analyzed alterations of the entire BA metabolic pathway in response to a HF diet without the addition of cholesterol and BA in the diet. Additionally, we evaluated the relationships between BA metabolism and some disorders, such as plasma transaminase activities and glucose intolerance induced by the HF diet. Acclimated WKAH/HkmSlc male rats (3 wk old) were divided into two groups fed a control or the HF diet for 22 wk. Fasting blood glucose was measured during the experimental period, and an intraperitoneal glucose tolerance test was performed at week 21. As a result, ingestion of the HF diet selectively increased the concentration of taurocholic acid in the bile and small intestinal contents as well as deoxycholic acid in the large intestinal contents and feces. These results indicated a selective increase of 12a-hydroxylated BA concentrations in response to the HF diet. Moreover, fecal 12a-hydroxylated BA concentration was positively correlated with cumulative energy intake, visceral adipose tissue weight, and glucose intolerance. The present study suggests that fecal 12a-hydroxylated BA is a non-invasive marker that can detect the early phase of glucose intolerance.

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“…The key-enzyme in that pathway is a P450-like enzyme that catalyses the specific and irreversible 7β-hydroxylation. On this topic, a recent work by Kollerov et al [ 98 ] describes several DCA modifying filamentous fungi strains (mostly ascomycetes and zygomycetes): the highest 7β-hydroxylase activity level was found in Fusarium merismoides VKM F-2310.…”

Section: Reviewmentioning

confidence: 99%

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

Tonin

Arends

2018

Beilstein J. Org. Chem.

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Ursodeoxycholic acid (UDCA) is a pharmaceutical ingredient widely used in clinics. As bile acid it solubilizes cholesterol gallstones and improves the liver function in case of cholestatic diseases. UDCA can be obtained from cholic acid (CA), which is the most abundant and least expensive bile acid available. The now available chemical routes for the obtainment of UDCA yield about 30% of final product. For these syntheses several protection and deprotection steps requiring toxic and dangerous reagents have to be performed, leading to the production of a series of waste products. In many cases the cholic acid itself first needs to be prepared from its taurinated and glycilated derivatives in the bile, thus adding to the complexity and multitude of steps involved of the synthetic process. For these reasons, several studies have been performed towards the development of microbial transformations or chemoenzymatic procedures for the synthesis of UDCA starting from CA or chenodeoxycholic acid (CDCA). This promising approach led several research groups to focus their attention on the development of biotransformations with non-pathogenic, easy-to-manage microorganisms, and their enzymes. In particular, the enzymatic reactions involved are selective hydrolysis, epimerization of the hydroxy functions (by oxidation and subsequent reduction) and the specific hydroxylation and dehydroxylation of suitable positions in the steroid rings. In this minireview, we critically analyze the state of the art of the production of UDCA by several chemical, chemoenzymatic and enzymatic routes reported, highlighting the bottlenecks of each production step. Particular attention is placed on the precursors availability as well as the substrate loading in the process. Potential new routes and recent developments are discussed, in particular on the employment of flow-reactors. The latter technology allows to develop processes with shorter reaction times and lower costs for the chemical and enzymatic reactions involved.

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Deoxycholic acid transformations catalyzed by selected filamentous fungi

Cited by 21 publications

References 32 publications

Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

Alteration of Bile Acid Metabolism by a High-Fat Diet Is Associated with Plasma Transaminase Activities and Glucose Intolerance in Rats

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

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