nach oben

European Journal of Nutrition

Erschienen in:

20.03.2022 | Original Contribution

Characterization of metabolites and biomarkers for the probiotic effects of Clostridium cochlearium on high-fat diet-induced obese C57BL/6 mice

verfasst von: Fei Yang, Wenjun Zhu, Paba Edirisuriya, Qing Ai, Kai Nie, Xiangming Ji, Kequan Zhou

Erschienen in: European Journal of Nutrition | Ausgabe 4/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Probiotic species of butyrate producers have been investigated for the potential in preventing and treating obesity and overweight. However, Clostridium cochlearium has not been linked with any health benefits. We hypothesized that C. cochlearium could be a promising new probiotic with health benefits in improving body weight control and insulin sensitivity.

Methods

Productions of short-chain fatty acids (SCFAs) were characterized for C. cochlearium by NMR and GC–MS analyses. Probiotic effects of C. cochlearium were evaluated through diet-induced obese (DIO) C57BL/6 mice. The influence of C. cochlearium administration on gut SCFAs was measured using GC–MS. LC–MS-based untargeted metabolomic profiling and multivariate analysis were used to assess the serum metabolic alteration, identify biomarkers and pathways in response to the C. cochlearium administration.

Results

After 17 weeks of diet intervention, body weight gain of CC group (fed with a high-fat diet supplemented with C. cochlearium) showed a 21.86% reduction from the high-fat diet (HF) control group (P < 0.001), which was specifically reflected on the significantly lowered fat mass (CC vs HF, 17.19 g vs 22.86 g, P < 0.0001) and fat percentage (CC vs HF, 41.25% vs 47.10%, P < 0.0001), and increased lean percentage (CC vs HF, 46.63% vs 43.72%, P < 0.05). C. cochlearium administration significantly reduced fasting blood glucose from week 8 (P < 0.05 or 0.01), and eventually improved insulin sensitivity (HOMA-IR, CC vs HF, 63.77 vs 143.13, P < 0.05). Overall lowered levels of SCFAs were observed in the gut content of CC group. Metabolomic analysis enabled the identification of 53 discriminatory metabolites and 24 altered pathways between CC and HF groups. In particularly, most of the pathway-matched metabolites showed positive correlations with body weight, which included glutamate, phenylalanine, ornithine, PCs, LPCs, AcCas, proline, 5,6-dihydrouracil, pyroglutamic acid, and 1-pyrroline-4-hydroxy-2-carboxylate.

Conclusions

The beneficial effects of C. cochlearium could be related to its ability to restore certain obesity-driven biomarkers and pathways, especially downregulating pathways related to specific amino acids, PCs, LPCs and AcCas. Further research is warranted to investigate related metabolites and metabolic pathways. C. cochlearium may be developed as a promising new probiotic for the prevention or alleviation of obesity and diabetes in human.

Nur mit Berechtigung zugänglich

World Health Organization (2018) Obesity and overweight. https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 15 Sept 2021

Sanz Y, Santacruz A, Gauffin P (2010) Gut microbiota in obesity and metabolic disorders. Proc Nutr Soc 69:434–441. https://doi.org/10.1017/S0029665110001813CrossRefPubMed

Muller TD, Clemmensen C, Finan B, DiMarchi RD, Tschop MH (2018) Anti-obesity therapy: from rainbow pills to polyagonists. Pharmacol Rev 70:712–746. https://doi.org/10.1124/pr.117.014803CrossRefPubMed

Heymsfield SB, Wadden TA (2017) Mechanisms, pathophysiology, and management of obesity. N Engl J Med 376:254–266. https://doi.org/10.1056/NEJMra1514009CrossRefPubMed

Kobyliak N, Conte C, Cammarota G, Haley AP, Styriak I, Gaspar L et al (2016) Probiotics in prevention and treatment of obesity: a critical view. Nutr Metab. https://doi.org/10.1186/s12986-016-0067-0CrossRef

Sekirov I, Russell SL, Antunes LC, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev 90:859–904. https://doi.org/10.1152/physrev.00045.2009CrossRefPubMed

Sanders ME (2008) Probiotics: definition, sources, selection, and uses. Clin Infect Dis 46(Suppl 2):S58-61. https://doi.org/10.1086/523341CrossRefPubMed

Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G et al (2016) The gut microbiota and host health: a new clinical frontier. Gut 65:330–339. https://doi.org/10.1136/gutjnl-2015-309990CrossRefPubMed

Rouxinol-Dias AL, Pinto AR, Janeiro C, Rodrigues D, Moreira M, Dias J et al (2016) Probiotics for the control of obesity—its effect on weight change. Porto Biomed J 1:12–24. https://doi.org/10.1016/j.pbj.2016.03.005CrossRefPubMedPubMedCentral

10.

Raoult D (2009) Probiotics and obesity: a link? Nat Rev Microbiol 7:616. https://doi.org/10.1038/nrmicro2209CrossRefPubMed

11.

Chang CS, Ruan JW, Kao CY (2019) An overview of microbiome based strategies on anti-obesity. Kaohsiung J Med Sci 35:7–16. https://doi.org/10.1002/kjm2.12010CrossRefPubMed

12.

Udayappan S, Manneras-Holm L, Chaplin-Scott A, Belzer C, Herrema H, Dallinga-Thie GM et al (2016) Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice. NPJ Biofilms Microbi. https://doi.org/10.1038/npjbiofilms.2016.9CrossRef

13.

Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M et al (2009) Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58:1509–1517. https://doi.org/10.2337/db08-1637CrossRefPubMedPubMedCentral

14.

Chen W, Zhang S, Wu J, Ye T, Wang S, Wang P et al (2020) Butyrate-producing bacteria and the gut-heart axis in atherosclerosis. Clin Chim Acta 507:236–241. https://doi.org/10.1016/j.cca.2020.04.037CrossRefPubMed

15.

Fu X, Liu Z, Zhu C, Mou H, Kong Q (2019) Nondigestible carbohydrates, butyrate, and butyrate-producing bacteria. Crit Rev Food Sci Nutr 59:S130–S152. https://doi.org/10.1080/10408398.2018.1542587CrossRefPubMed

16.

Yutin N, Galperin MY (2013) A genomic update on clostridial phylogeny: gram-negative spore formers and other misplaced clostridia. Environ Microbiol 15:2631–2641. https://doi.org/10.1111/1462-2920.12173CrossRefPubMedPubMedCentral

17.

Sanchez Ramos L, Rodloff AC (2018) Identification of Clostridium species using the VITEK((R)) MS. Anaerobe 54:217–223. https://doi.org/10.1016/j.anaerobe.2018.01.007CrossRefPubMed

18.

Ling Z, Liu X, Cheng Y, Luo Y, Yuan L, Li L et al (2015) Clostridium butyricum combined with Bifidobacterium infantis probiotic mixture restores fecal microbiota and attenuates systemic inflammation in mice with antibiotic-associated diarrhea. Biomed Res Int. https://doi.org/10.1155/2015/582048CrossRefPubMedPubMedCentral

19.

Sun YY, Li M, Li YY, Li LX, Zhai WZ, Wang P et al (2018) The effect of Clostridium butyricum on symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial. Sci Rep. https://doi.org/10.1038/s41598-018-21241-zCrossRefPubMedPubMedCentral

20.

Shang H, Sun J, Chen YQ (2016) Clostridium butyricum CGMCC0313.1 modulates lipid profile, insulin resistance and colon homeostasis in obese mice. PLoS ONE 11:e0154373. https://doi.org/10.1371/journal.pone.0154373CrossRefPubMedPubMedCentral

21.

Jia L, Li D, Feng N, Shamoon M, Sun Z, Ding L et al (2017) Anti-diabetic effects of Clostridium butyricum CGMCC0313.1 through promoting the growth of gut butyrate-producingbacteria in type 2 diabetic mice. Sci Rep. https://doi.org/10.1038/s41598-017-07335-0CrossRefPubMedPubMedCentral

22.

Buckel W, Barker H (1974) Two pathways of glutamate fermentation by anaerobic bacteria. J Bacteriol 117:1248–1260. https://doi.org/10.1128/jb.117.3.1248-1260.1974CrossRefPubMedPubMedCentral

23.

Leutbecher U, Böcher R, Linder D, BUCKEL W (1992) Glutamate mutase from Clostridium cochlearium: purification, cobamide content and stereospecific inhibitors. Eur J Biochem 205:759–765. https://doi.org/10.1111/j.1432-1033.1992.tb16840.xCrossRefPubMed

24.

Lee W, Fujisawa T, Kawamura S, Itoh K, Mitsuoka T (1991) Isolation and identification of clostridia from the intestine of laboratory animals. Lab Anim 25:9–15. https://doi.org/10.1258/002367791780808158CrossRefPubMed

25.

Finegold SM, Molitoris D, Song Y, Liu C, Vaisanen M-L, Bolte E et al (2002) Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis 35:S6-16. https://doi.org/10.1086/341914CrossRefPubMed

26.

Duncan SH, Louis P, Flint HJ (2004) Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl Environ Microbiol 70:5810–5817. https://doi.org/10.1128/AEM.70.10.5810-5817.2004CrossRefPubMedPubMedCentral

27.

Louis P, Young P, Holtrop G, Flint HJ (2010) Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environ Microbiol 12:304–314. https://doi.org/10.1111/j.1462-2920.2009.02066.xCrossRefPubMed

28.

Ippagunta SM, Kharitonenkov A, Adams AC, Hillgartner FB (2018) Cholic acid supplementation of a high-fat obesogenic diet suppresses hepatic triacylglycerol accumulation in mice via a fbroblast growth factor 21–dependent mechanism. J Nutr 148:510–517. https://doi.org/10.1093/jn/nxy022CrossRefPubMed

29.

Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E, Lindon JC et al (2007) Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc 2:2692–2703. https://doi.org/10.1038/nprot.2007.376CrossRefPubMed

30.

Kaspar H (2009) Amino acid analysis in biological fluids by GC-MS. PhD, University of Regensburg

31.

Zheng X, Qiu Y, Zhong W, Baxter S, Su M, Li Q et al (2013) A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids. Metabolomics 9:818–827. https://doi.org/10.1007/s11306-013-0500-6CrossRefPubMedPubMedCentral

32.

Dunn WB, Broadhurst D, Begley P, Zelena E, Francis-McIntyre S, Anderson N et al (2011) Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc 6:1060–1083. https://doi.org/10.1038/nprot.2011.335CrossRefPubMed

33.

Lu D, Xue L, Feng C, Wu C, Xie C, Gonzalez FJ et al (2019) A systemic workflow for profiling metabolome and lipidome in tissue. J Chromatogr A 1589:105–115. https://doi.org/10.1016/j.chroma.2018.12.061CrossRefPubMed

34.

Gong J, Feng Z, Peterson AL, Carr JF, Lu X, Zhao H et al (2021) The pentose phosphate pathway mediates hyperoxia-induced lung vascular dysgenesis and alveolar simplification in neonates. JCI Insight 6:e137594. https://doi.org/10.1172/jci.insight.137594CrossRefPubMedCentral

35.

Kataoka N, Vangnai AS, Pongtharangkul T, Yakushi T, Matsushita K (2017) Butyrate production under aerobic growth conditions by engineered Escherichia coli. J Biosci Bioeng 123:562–568. https://doi.org/10.1016/j.jbiosc.2016.12.008CrossRefPubMed

36.

Jing L, Guigonis J-M, Borchiellini D, Durand M, Pourcher T, Ambrosetti D (2019) LC-MS based metabolomic profiling for renal cell carcinoma histologic subtypes. Sci Rep 9:1–10. https://doi.org/10.1038/s41598-019-52059-yCrossRef

37.

Borga M, West J, Bell JD, Harvey NC, Romu T, Heymsfield SB et al (2018) Advanced body composition assessment: from body mass index to body composition profiling. J Investig Med 66:1–9. https://doi.org/10.1136/jim-2018-000722CrossRefPubMedPubMedCentral

38.

Segal KR, Dunaif A, Gutin B, Albu J, Nyman A, Pi-Sunyer FX (1987) Body composition, not body weight, is related to cardiovascular disease risk factors and sex hormone levels in men. J Clin Invest 80:1050–1055. https://doi.org/10.1172/JCI113159CrossRefPubMedPubMedCentral

39.

Hardy OT, Czech MP, Corvera S (2012) What causes the insulin resistance underlying obesity? Curr Opin Endocrinol Diabetes Obes 19:81–87. https://doi.org/10.1097/MED.0b013e3283514e13CrossRefPubMedPubMedCentral

40.

Hill JO, Wyatt HR, Peters JC (2012) Energy balance and obesity. Circulation 126:126–132. https://doi.org/10.1161/CIRCULATIONAHA.111.087213CrossRefPubMedPubMedCentral

41.

Jéquier E (2002) Pathways to obesity. Int J Obes 26:S12–S17. https://doi.org/10.1038/sj.ijo.0802123CrossRef

42.

Hariri N, Thibault L (2010) High-fat diet-induced obesity in animal models. Nutr Res Rev 23:270–299. https://doi.org/10.1017/S0954422410000168CrossRefPubMed

43.

Kobyliak N, Conte C, Cammarota G, Haley AP, Styriak I, Gaspar L et al (2016) Probiotics in prevention and treatment of obesity: a critical view. Nutr Metab 13:1–13. https://doi.org/10.1186/s12986-016-0067-0CrossRef

44.

Baothman OA, Zamzami MA, Taher I, Abubaker J, Abu-Farha M (2016) The role of gut microbiota in the development of obesity and diabetes. Lipids Health Dis 15:1–8. https://doi.org/10.1186/s12944-016-0278-4CrossRef

45.

Anand S, Kaur H, Mande SS (2016) Comparative in silico analysis of butyrate production pathways in gut commensals and pathogens. Front Microbiol 7:1945. https://doi.org/10.3389/fmicb.2016.01945CrossRefPubMedPubMedCentral

46.

Cummings JH (1981) Short chain fatty acids in the human colon. Gut 22:763–779. https://doi.org/10.1136/gut.22.9.763CrossRefPubMedPubMedCentral

47.

Butel MJ (2014) Probiotics, gut microbiota and health. Med Mal Infect 44:1–8. https://doi.org/10.1016/j.medmal.2013.10.002CrossRefPubMed

48.

Yan F, Polk DB (2010) Probiotics: progress toward novel therapies for intestinal diseases. Curr Opin Gastroenterol 26:95–101. https://doi.org/10.1097/MOG.0b013e328335239aCrossRefPubMedPubMedCentral

49.

Liu H, Wang J, He T, Becker S, Zhang G, Li D et al (2018) Butyrate: a double-edged sword for health? Adv Nutr 9:21–29CrossRefPubMedPubMedCentral

50.

Chakraborti CK (2015) New-found link between microbiota and obesity. World J Gastrointest Pathophysiol 6:110–119. https://doi.org/10.4291/wjgp.v6.i4.110CrossRefPubMedPubMedCentral

51.

den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud D-J, Bakker BM (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54:2325–2340. https://doi.org/10.1194/jlr.R036012CrossRef

52.

Fernandes J, Su W, Rahat-Rozenbloom S, Wolever T, Comelli E (2014) Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes. https://doi.org/10.1038/nutd.2014.23CrossRefPubMedPubMedCentral

53.

Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1031. https://doi.org/10.1038/nature05414CrossRefPubMed

54.

Murphy E, Cotter P, Healy S, Marques TM, O’sullivan O, Fouhy F et al (2010) Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59:1635–1642. https://doi.org/10.1136/gut.2010.215665CrossRefPubMed

55.

Schwiertz A, Taras D, Schäfer K, Beijer S, Bos NA, Donus C et al (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18:190–195. https://doi.org/10.1038/oby.2009.167CrossRefPubMed

56.

Tulipani S, Palau-Rodriguez M, Alonso AM, Cardona F, Marco-Ramell A, Zonja B et al (2016) Biomarkers of morbid obesity and prediabetes by metabolomic profiling of human discordant phenotypes. Clin Chim Acta 463:53–61. https://doi.org/10.1016/j.cca.2016.10.005CrossRefPubMed

57.

Würtz P, Soininen P, Kangas AJ, Rönnemaa T, Lehtimäki T, Kähönen M et al (2013) Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults. Diabetes Care 36:648–655. https://doi.org/10.2337/dc12-0895CrossRefPubMedPubMedCentral

58.

Sailer M, Dahlhoff C, Giesbertz P, Eidens MK, de Wit N, Rubio-Aliaga I et al (2013) Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome. PLoS ONE 8:e63950. https://doi.org/10.1371/journal.pone.0063950CrossRefPubMedPubMedCentral

59.

Lent-Schochet D, McLaughlin M, Ramakrishnan N, Jialal I (2019) Exploratory metabolomics of metabolic syndrome: a status report. World J Diabetes 10:23. https://doi.org/10.4239/wjd.v10.i1.23CrossRefPubMedPubMedCentral

60.

Monti LD, Casiraghi MC, Setola E, Galluccio E, Pagani MA, Quaglia L et al (2013) L-arginine enriched biscuits improve endothelial function and glucose metabolism: a pilot study in healthy subjects and a cross-over study in subjects with impaired glucose tolerance and metabolic syndrome. Metabolism 62:255–264. https://doi.org/10.1016/j.metabol.2012.08.004CrossRefPubMed

61.

Han X (2016) Lipidomics for studying metabolism. Nat Rev Endocrinol 12:668. https://doi.org/10.1038/nrendo.2016.98CrossRefPubMed

62.

Gross RW, Han X (2007) Lipidomics in diabetes and the metabolic syndrome. Meth Enzymol 433:73–90. https://doi.org/10.1016/S0076-6879(07)33004-8CrossRef

63.

Syme C, Czajkowski S, Shin J, Abrahamowicz M, Leonard G, Perron M et al (2016) Glycerophosphocholine metabolites and cardiovascular disease risk factors in adolescents: a cohort study. Circulation 134:1629–1636. https://doi.org/10.1161/CIRCULATIONAHA.116.022993CrossRefPubMed

64.

Cole LK, Vance JE, Vance DE (2012) Phosphatidylcholine biosynthesis and lipoprotein metabolism. Biochim Biophys Acta, Mol Cell Biol Lipids 1821:754–761. https://doi.org/10.1016/j.bbalip.2011.09.009CrossRef

65.

Law S-H, Chan M-L, Marathe GK, Parveen F, Chen C-H, Ke L-Y (2019) An updated review of lysophosphatidylcholine metabolism in human diseases. Int J Mol Sci 20:1149. https://doi.org/10.3390/ijms20051149CrossRefPubMedCentral

66.

Heimerl S, Fischer M, Baessler A, Liebisch G, Sigruener A, Wallner S et al (2014) Alterations of plasma lysophosphatidylcholine species in obesity and weight loss. PLoS ONE 9:e111348. https://doi.org/10.1371/journal.pone.0111348CrossRefPubMedPubMedCentral

67.

Barber MN, Risis S, Yang C, Meikle PJ, Staples M, Febbraio MA et al (2012) Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes. PLoS ONE 7:e41456. https://doi.org/10.1371/journal.pone.0041456CrossRefPubMedPubMedCentral

68.

Adeva-Andany MM, Calvo-Castro I, Fernández-Fernández C, Donapetry-García C, Pedre-Piñeiro AM (2017) Significance of L-carnitine for human health. IUBMB Life 69:578–594. https://doi.org/10.1002/iub.1646CrossRefPubMed

69.

Guasch-Ferré M, Ruiz-Canela M, Li J, Zheng Y, Bulló M, Wang DD et al (2019) Plasma acylcarnitines and risk of type 2 diabetes in a Mediterranean population at high cardiovascular risk. J Clin Endocrinol Metab 104:1508–1519. https://doi.org/10.1210/jc.2018-01000CrossRefPubMed

70.

Hoppel CL, Genuth SM (1982) Urinary excretion of acetylcarnitine during human diabetic and fasting ketosis. Am J Physiol Endocrinol Metab 243:E168–E172. https://doi.org/10.1152/ajpendo.1982.243.2.E168CrossRef

Titel: Characterization of metabolites and biomarkers for the probiotic effects of Clostridium cochlearium on high-fat diet-induced obese C57BL/6 mice
verfasst von: Fei Yang
Wenjun Zhu
Paba Edirisuriya
Qing Ai
Kai Nie
Xiangming Ji
Kequan Zhou
Publikationsdatum: 20.03.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 4/2022
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-022-02840-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Characterization of metabolites and biomarkers for the probiotic effects of Clostridium cochlearium on high-fat diet-induced obese C57BL/6 mice

Abstract

Purpose

Methods

Results

Conclusions

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Ist Fasten vor Koronarinterventionen wirklich nötig?

Typ-2-Diabetes: Ernährungsunsicherheit vervierfacht Risiko für schwere Hypoglykämien

Mehr Brustkrebs, aber weniger andere gynäkologische Tumoren mit Levonorgestrel-IUS

GLP-1-Agonist Semaglutid wirkt kardio- und nephroprotektiv

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2022

Effect of maternal curcumin supplementation on intestinal damage and the gut microbiota in male mice offspring with intra-uterine growth retardation

Suppression of high-fat-diet-induced obesity in mice by dietary folic acid supplementation is linked to changes in gut microbiota

Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia

Dietary omega-3 polyunsaturated fatty acid and alpha-linolenic acid are associated with physical capacity measure but not muscle mass in older women 65–72 years

The DONALD study as a longitudinal sensor of nutritional developments: iodine and salt intake over more than 30 years in German children

Differential impact of cold and hot tea extracts on tyrosine phosphatases regulating insulin receptor activity: a focus on PTP1B and LMW-PTP

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Ist Fasten vor Koronarinterventionen wirklich nötig?

Typ-2-Diabetes: Ernährungsunsicherheit vervierfacht Risiko für schwere Hypoglykämien

Mehr Brustkrebs, aber weniger andere gynäkologische Tumoren mit Levonorgestrel-IUS

GLP-1-Agonist Semaglutid wirkt kardio- und nephroprotektiv

Update Innere Medizin