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Metabolites
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Bile Acid Metabolism and Gut Microbiota
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Bile Acid Metabolism and Gut Microbiota

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Microbiology and Ecological Metabolomics".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 24822

Special Issue Editors

Dr. Ulrike E. Rolle-Kampczyk

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Guest Editor
Department of Molecular Systems Biology, Helmholtz Zentrum für Umweltforschung, 15, 04318 Leipzig, Germany
Interests: metabolomics (targeted/untargeted); human biomonitoring; microbiome research; mass spectrometry
Special Issues, Collections and Topics in MDPI journals
Dr. Beatrice Engelmann

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Guest Editor
Helmholtz Zentrum für Umweltforschung, 15, 04318 Leipzig, Germany
Interests: targeted and untargeted metabolomics; LC-MS/MS-based methodology development; biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Sven-Bastiaan Haange

E-Mail Website
Guest Editor
Helmholtz Zentrum für Umweltforschung, 15, 04318 Leipzig, Germany
Interests: intestinal microbiome; multi-omics; metabolomics (targeted/untargeted); metaproteomics; 16S rRNA gene sequencing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bile acids, which have a primary function in nutrient absorption, are also heavily involved in gut–microbiota host signalling. Primary bile acids are synthesized in the liver by the host and then conjugated before release into the intestinal tract. Here, they can be reabsorbed and transported with the portal blood to the liver, forming the enterohepatic circulation. In the gut, conjugated primary bile acids can be deconjugated, followed by conversion to secondary bile acids by specific bacteria. The bile acids present in the gut influence the composition of the gut microbiota because of their differing bactericidal properties. In addition, secondary bile acids are reabsorbed in the colon and are known to act as signalling molecules in several host processes including glucose homeostasis, immune system regulation and lipogenesis. Thus, bile acid and gut microbiota research is a compelling field with imperative health implications.

This Special Issue of Metabolites, “Bile Acids and Gut Microbiota”, will be dedicated to dealing with interactions between bile acids and the gut microbiota as well as the resulting host effects. This Issue is not only intended for results from basic research (cell or animal models) but is also open to results from epidemiological studies. In addition, new measurement methods, bioinformatical tools and data analysis concepts are welcome.

Dr. Ulrike E. Rolle-Kampczyk
Dr. Beatrice Engelmann
Dr. Sven-Bastiaan Haange
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bile acids
  • gut microbiota
  • host interactions
  • intestinal crosstalk
  • microbial regulation

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Published Papers (7 papers)

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Research

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28 pages, 7338 KiB  
Article
Ring Trial on Quantitative Assessment of Bile Acids Reveals a Method- and Analyte-Specific Accuracy and Reproducibility
by Sven-Bastiaan Haange, Andreas Till, Per-Olof Bergh, Günter Fauler, Michael Gigl, Anita Löfgren-Sandblom, Frank G. Schaap, Thomas Clavel, Christian Trautwein, Wiebke Fenske, Karin Kleigrewe, Hanns-Ulrich Marschall, Steven W. M. Olde Damink, Tarek Moustafa, Martin von Bergen and Ulrike Rolle-Kampczyk
Metabolites 2022, 12(7), 583; https://doi.org/10.3390/metabo12070583 - 23 Jun 2022
Cited by 5 | Viewed by 2431
Abstract
Bile acids are a key mediator of the molecular microbiome-host interaction, and various mass spectrometry-based assays have been developed in the recent decade to quantify a wide range of bile acids. We compare existing methodologies to harmonize them. Methodology for absolute quantification of [...] Read more.
Bile acids are a key mediator of the molecular microbiome-host interaction, and various mass spectrometry-based assays have been developed in the recent decade to quantify a wide range of bile acids. We compare existing methodologies to harmonize them. Methodology for absolute quantification of bile acids from six laboratories in Europe were compared for the quantification of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) and conjugated products glycocholic acid (GCA) and taurocholic acid (TCA). For the bacterially modified secondary bile acids, the quantification of deoxycholic acid (DCA) and lithocholic acid (LCA) was compared. For the murine bile acids, we used the primary muricholic acids (α-MCA and, β-MCA) and the intestinally produced secondary bile acid muricholic (ω-MCA). The standards were spiked into methanol:water (1:1) mix as well as in human and murine serum at either low concentration range (150–3000 nM) or high concentration range (1500–40,000 nM). The precision was better for higher concentrations. Measurements for the hydrophobic unconjugated bile acids LCA and ω-MCA were the most challenging. The quality assessments were generally very similar, and the comprehensive analyses demonstrated that data from chosen locations can be used for comparisons between studies. Full article
(This article belongs to the Special Issue Bile Acid Metabolism and Gut Microbiota)
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21 pages, 4080 KiB  
Article
Metabolic Profile and Metabolite Analyses in Extreme Weight Responders to Gastric Bypass Surgery
by Charlotte M. Fries, Sven-Bastiaan Haange, Ulrike Rolle-Kampczyk, Andreas Till, Mathis Lammert, Linda Grasser, Evelyn Medawar, Arne Dietrich, Annette Horstmann, Martin von Bergen and Wiebke K. Fenske
Metabolites 2022, 12(5), 417; https://doi.org/10.3390/metabo12050417 - 6 May 2022
Cited by 4 | Viewed by 3061
Abstract
Background: Roux-en-Y gastric bypass (RYGB) surgery belongs to the most frequently performed surgical therapeutic strategies against adiposity and its comorbidities. However, outcome is limited in a substantial cohort of patients with inadequate primary weight loss or considerable weight regain. In this study, gut [...] Read more.
Background: Roux-en-Y gastric bypass (RYGB) surgery belongs to the most frequently performed surgical therapeutic strategies against adiposity and its comorbidities. However, outcome is limited in a substantial cohort of patients with inadequate primary weight loss or considerable weight regain. In this study, gut microbiota composition and systemically released metabolites were analyzed in a cohort of extreme weight responders after RYGB. Methods: Patients (n = 23) were categorized based on excess weight loss (EWL) at a minimum of two years after RYGB in a good responder (EWL 93 ± 4.3%) or a bad responder group (EWL 19.5 ± 13.3%) for evaluation of differences in metabolic outcome, eating behavior and gut microbiota taxonomy and metabolic activity. Results: Mean BMI was 47.2 ± 6.4 kg/m2 in the bad vs. 26.6 ± 1.2 kg/m2 in the good responder group (p = 0.0001). We found no difference in hunger and satiety sensation, in fasting or postprandial gut hormone release, or in gut microbiota composition between both groups. Differences in weight loss did not reflect in metabolic outcome after RYGB. While fecal and circulating metabolite analyses showed higher levels of propionate (p = 0.0001) in good and valerate (p = 0.04) in bad responders, respectively, conjugated primary and secondary bile acids were higher in good responders in the fasted (p = 0.03) and postprandial state (GCA, p = 0.02; GCDCA, p = 0.02; TCA, p = 0.01; TCDCA, p = 0.02; GDCA, p = 0.05; GUDCA, p = 0.04; TLCA, p = 0.04). Conclusions: Heterogenous weight loss response to RYGB surgery separates from patients’ metabolic outcome, and is linked to unique serum metabolite signatures post intervention. These findings suggest that the level of adiposity reduction alone is insufficient to assess the metabolic success of RYGB surgery, and that longitudinal metabolite profiling may eventually help us to identify markers that could predict individual adiposity response to surgery and guide patient selection and counseling. Full article
(This article belongs to the Special Issue Bile Acid Metabolism and Gut Microbiota)
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11 pages, 1983 KiB  
Article
Evaluation of the Risk of Clostridium difficile Infection Using a Serum Bile Acid Profile
by Tadakuni Monma, Junichi Iwamoto, Akira Honda, Hajime Ueda, Fumio Kakizaki, Shoichiro Yara, Teruo Miyazaki and Tadashi Ikegami
Metabolites 2022, 12(4), 331; https://doi.org/10.3390/metabo12040331 - 6 Apr 2022
Cited by 2 | Viewed by 1965
Abstract
Since intestinal secondary bile acids (BAs) prevent Clostridium difficile infection (CDI), the serum BA profile may be a convenient biomarker for CDI susceptibility in human subjects. To verify this hypothesis, we investigated blood samples from 71 patients of the Division of Gastroenterology and [...] Read more.
Since intestinal secondary bile acids (BAs) prevent Clostridium difficile infection (CDI), the serum BA profile may be a convenient biomarker for CDI susceptibility in human subjects. To verify this hypothesis, we investigated blood samples from 71 patients of the Division of Gastroenterology and Hepatology at the time of admission (prior to antibiotic use and CDI onset). Twelve patients developed CDI during hospitalization, and the other 59 patients did not. The serum unconjugated deoxycholic acid (DCA)/[DCA + unconjugated cholic acid (CA)] ratio on admission was significantly lower in patients who developed CDI than in patients who did not develop CDI (p < 0.01) and in 46 healthy controls (p < 0.0001). Another unconjugated secondary BA ratio, 3β-hydroxy (3βOH)-BAs/(3βOH + 3αOH-BAs), was also significantly lower in patients who developed CDI than in healthy controls (p < 0.05) but was not significantly different between patients who developed and patients who did not develop CDI. A receiver operating characteristic (ROC) curve determined a cut-off point of DCA/(DCA + CA) < 0.349 that optimally discriminated on admission the high-risk patients who would develop CDI (sensitivity 91.7% and specificity 64.4%). In conclusion, a decreased serum DCA/(DCA + CA) ratio on admission strongly correlated with CDI onset during hospitalization in patients with gastrointestinal and hepatobiliary diseases. Serum BA composition could be a helpful biomarker for predicting susceptibility to CDI. Full article
(This article belongs to the Special Issue Bile Acid Metabolism and Gut Microbiota)
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13 pages, 1645 KiB  
Article
A Potential Role for Bile Acid Signaling in Celiac Disease-Associated Fatty Liver
by Paul Manka, Svenja Sydor, Julia M. Schänzer-Ocklenburg, Malte Brandenburg, Jan Best, Ramiro Vilchez-Vargas, Alexander Link, Dominik Heider, Susanne Brodesser, Anja Figge, Andreas Jähnert, Jason D. Coombes, Francisco Javier Cubero, Alisan Kahraman, Moon-Sung Kim, Julia Kälsch, Sonja Kinner, Klaas Nico Faber, Han Moshage, Guido Gerken, Wing-Kin Syn, Ali Canbay and Lars P. Bechmannadd Show full author list remove Hide full author list
Metabolites 2022, 12(2), 130; https://doi.org/10.3390/metabo12020130 - 30 Jan 2022
Cited by 5 | Viewed by 3819
Abstract
Celiac disease (CeD) is a chronic autoimmune disorder characterized by an intolerance to storage proteins of many grains. CeD is frequently associated with liver damage and steatosis. Bile acid (BA) signaling has been identified as an important mediator in gut–liver interaction and the [...] Read more.
Celiac disease (CeD) is a chronic autoimmune disorder characterized by an intolerance to storage proteins of many grains. CeD is frequently associated with liver damage and steatosis. Bile acid (BA) signaling has been identified as an important mediator in gut–liver interaction and the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we aimed to analyze BA signaling and liver injury in CeD patients. Therefore, we analyzed data of 20 CeD patients on a gluten-free diet compared to 20 healthy controls (HC). We furthermore analyzed transaminase levels, markers of cell death, BA, and fatty acid metabolism. Hepatic steatosis was determined via transient elastography, by MRI and non-invasive scores. In CeD, we observed an increase of the apoptosis marker M30 and more hepatic steatosis as compared to HC. Fibroblast growth factor 19 (FGF19) was repressed in CeD, while low levels were associated with steatosis, especially in patients with high levels of anti-tissue transglutaminase antibodies (anti-tTG). When comparing anti-tTG-positive CeD patients to individuals without detectable anti-tTG levels, hepatic steatosis was accentuated. CeD patients with significant sonographic steatosis (defined by CAP ≥ 283 db/m) were exclusively anti-tTG-positive. In summary, our results suggest that even in CeD patients in clinical remission under gluten-free diet, alterations in gut–liver axis, especially BA signaling, might contribute to steatotic liver injury and should be further addressed in future studies and clinical practice. Full article
(This article belongs to the Special Issue Bile Acid Metabolism and Gut Microbiota)
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Review

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10 pages, 875 KiB  
Review
Farnesoid X Receptor, Bile Acid Metabolism, and Gut Microbiota
by Hideki Mori, Gianluca Svegliati Baroni, Marco Marzioni, Francesca Di Nicola, Pierangelo Santori, Luca Maroni, Ludovico Abenavoli and Emidio Scarpellini
Metabolites 2022, 12(7), 647; https://doi.org/10.3390/metabo12070647 - 14 Jul 2022
Cited by 27 | Viewed by 3791
Abstract
Obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) are characterized by the concepts of lipo- and glucotoxicity. NAFLD is characterized by the accumulation of different lipidic species within the hepatocytes. Bile acids (BA), derived from cholesterol, and conjugated and stored in [...] Read more.
Obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) are characterized by the concepts of lipo- and glucotoxicity. NAFLD is characterized by the accumulation of different lipidic species within the hepatocytes. Bile acids (BA), derived from cholesterol, and conjugated and stored in the gallbladder, help the absorption/processing of lipids, and modulate host inflammatory responses and gut microbiota (GM) composition. The latter is the new “actor” that links the GI tract and liver in NAFLD pathogenesis. In fact, the discovery and mechanistic characterization of hepatic and intestinal farnesoid X receptor (FXR) shed new light on the gut–liver axis. We conducted a search on the main medical databases for original articles, reviews, meta-analyses of randomized clinical trials, and case series using the following keywords, their acronyms, and their associations: farnesoid X receptor, bile acids metabolism, gut microbiota, dysbiosis, and liver steatosis. Findings on the synthesis, metabolism, and conjugation processes of BAs, and their action on FXR, change the understanding of NAFLD physiopathology. In detail, BAs act as ligands to several FXRs with GM modulation. On the other hand, the BAs pool is modulated by GM, thus, regulating FXRs functioning in the frame of liver fat deposition and fibrosis development. In conclusion, BAs passed from their role of simple lipid absorption and metabolism agents to messengers between the gut and liver, modulated by GM. Full article
(This article belongs to the Special Issue Bile Acid Metabolism and Gut Microbiota)
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14 pages, 1640 KiB  
Review
New Kids on the Block: Bile Salt Conjugates of Microbial Origin
by Ümran Ay, Martin Leníček, Arno Classen, Steven W. M. Olde Damink, Carsten Bolm and Frank G. Schaap
Metabolites 2022, 12(2), 176; https://doi.org/10.3390/metabo12020176 - 13 Feb 2022
Cited by 9 | Viewed by 3619
Abstract
Biotransformation of host bile salts by gut microbes results in generation of secondary bile salt species that have biological and physicochemical properties that are distinct from the parent compounds. There is increased awareness that a bile salt–gut microbiome axis modulates various processes in [...] Read more.
Biotransformation of host bile salts by gut microbes results in generation of secondary bile salt species that have biological and physicochemical properties that are distinct from the parent compounds. There is increased awareness that a bile salt–gut microbiome axis modulates various processes in the host, including innate and adaptive immunity, by interaction of microbial bile salt metabolites with host receptors. Omics and targeted approaches have vastly expanded the number and repertoire of secondary bile salt species. A new class of microbial bile salt metabolites was reported in 2020 and comprises bile salts that are conjugated by microbial enzymes. Amino acids other than those employed by host enzymes (glycine and taurine) are used as substrates in the formation of these microbial bile salt conjugates (MBSCs). Leucocholic acid, phenylalanocholic acid and tyrosocholic acid were the first MBSCs identified in mice and humans. The number of distinct MBSCs is now approaching 50, with variation both at the level of bile salt and amino acid employed for conjugation. Evidence is emerging that MBSC generation is a common feature of human gut bacteria, and initial links with disease states have been reported. In this review, we discuss this intriguing new class of secondary bile salts, with yet enigmatic function. Full article
(This article belongs to the Special Issue Bile Acid Metabolism and Gut Microbiota)
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14 pages, 5243 KiB  
Review
The Interaction between the Gut Microbiome and Bile Acids in Cardiometabolic Diseases
by Cengiz Callender, Ilias Attaye and Max Nieuwdorp
Metabolites 2022, 12(1), 65; https://doi.org/10.3390/metabo12010065 - 11 Jan 2022
Cited by 15 | Viewed by 3720
Abstract
Cardio-metabolic diseases (CMD) are a spectrum of diseases (e.g., type 2 diabetes, atherosclerosis, non-alcohol fatty liver disease (NAFLD), and metabolic syndrome) that are among the leading causes of morbidity and mortality worldwide. It has long been known that bile acids (BA), which are [...] Read more.
Cardio-metabolic diseases (CMD) are a spectrum of diseases (e.g., type 2 diabetes, atherosclerosis, non-alcohol fatty liver disease (NAFLD), and metabolic syndrome) that are among the leading causes of morbidity and mortality worldwide. It has long been known that bile acids (BA), which are endogenously produced signalling molecules from cholesterol, can affect CMD risk and progression and directly affect the gut microbiome (GM). Moreover, studies focusing on the GM and CMD risk have dramatically increased in the past decade. It has also become clear that the GM can function as a “new” endocrine organ. BA and GM have a complex and interdependent relationship with several CMD pathways. This review aims to provide a comprehensive overview of the interplay between BA metabolism, the GM, and CMD risk and progression. Full article
(This article belongs to the Special Issue Bile Acid Metabolism and Gut Microbiota)
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