Targeted metabolomics reveals plasma short-chain fatty acids are associated with metabolic dysfunction-associated steatotic liver disease
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Targeted metabolomics reveals plasma short-chain fatty acids are associated with metabolic dysfunction-associated steatotic liver disease. / Thing, Mira; Werge, Mikkel Parsberg; Kimer, Nina; Hetland, Liv Eline; Rashu, Elias Badal; Nabilou, Puria; Junker, Anders Ellekaer; Galsgaard, Elisabeth Douglas; Bendtsen, Flemming; Laupsa-Borge, Johnny; McCann, Adrian; Gluud, Lise Lotte.
I: BMC Gastroenterology, Bind 24, Nr. 1, 43, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Targeted metabolomics reveals plasma short-chain fatty acids are associated with metabolic dysfunction-associated steatotic liver disease
AU - Thing, Mira
AU - Werge, Mikkel Parsberg
AU - Kimer, Nina
AU - Hetland, Liv Eline
AU - Rashu, Elias Badal
AU - Nabilou, Puria
AU - Junker, Anders Ellekaer
AU - Galsgaard, Elisabeth Douglas
AU - Bendtsen, Flemming
AU - Laupsa-Borge, Johnny
AU - McCann, Adrian
AU - Gluud, Lise Lotte
N1 - Publisher Copyright: © 2024, The Author(s).
PY - 2024
Y1 - 2024
N2 - Background: Alterations in the production of short-chain fatty acids (SCFAs) may reflect disturbances in the gut microbiota and have been linked to metabolic dysfunction-associated steatotic liver disease (MASLD). We assessed plasma SCFAs in patients with MASLD and healthy controls. Methods: Fasting venous blood samples were collected and eight SCFAs were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). Relative between-group differences in circulating SCFA concentrations were estimated by linear regression, and the relation between SCFA concentrations, MASLD, and fibrosis severity was investigated using logistic regression. Results: The study includes 100 patients with MASLD (51% with mild/no fibrosis and 49% with significant fibrosis) and 50 healthy controls. Compared with healthy controls, MASLD patients had higher plasma concentrations of propionate (21.8%, 95% CI 3.33 to 43.6, p = 0.02), formate (21.9%, 95% CI 6.99 to 38.9, p = 0.003), valerate (35.7%, 95% CI 4.53 to 76.2, p = 0.02), and α-methylbutyrate (16.2%, 95% CI 3.66 to 30.3, p = 0.01) but lower plasma acetate concentrations (− 30.0%, 95% CI − 40.4 to − 17.9, p < 0.001). Among patients with MASLD, significant fibrosis was positively associated with propionate (p = 0.02), butyrate (p = 0.03), valerate (p = 0.03), and α-methylbutyrate (p = 0.02). Six of eight SCFAs were significantly increased in F4 fibrosis. Conclusions: In the present study, SCFAs were associated with MASLD and fibrosis severity, but further research is needed to elucidate the potential mechanisms underlying our observations and to assess the possible benefit of therapies modulating gut microbiota.
AB - Background: Alterations in the production of short-chain fatty acids (SCFAs) may reflect disturbances in the gut microbiota and have been linked to metabolic dysfunction-associated steatotic liver disease (MASLD). We assessed plasma SCFAs in patients with MASLD and healthy controls. Methods: Fasting venous blood samples were collected and eight SCFAs were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). Relative between-group differences in circulating SCFA concentrations were estimated by linear regression, and the relation between SCFA concentrations, MASLD, and fibrosis severity was investigated using logistic regression. Results: The study includes 100 patients with MASLD (51% with mild/no fibrosis and 49% with significant fibrosis) and 50 healthy controls. Compared with healthy controls, MASLD patients had higher plasma concentrations of propionate (21.8%, 95% CI 3.33 to 43.6, p = 0.02), formate (21.9%, 95% CI 6.99 to 38.9, p = 0.003), valerate (35.7%, 95% CI 4.53 to 76.2, p = 0.02), and α-methylbutyrate (16.2%, 95% CI 3.66 to 30.3, p = 0.01) but lower plasma acetate concentrations (− 30.0%, 95% CI − 40.4 to − 17.9, p < 0.001). Among patients with MASLD, significant fibrosis was positively associated with propionate (p = 0.02), butyrate (p = 0.03), valerate (p = 0.03), and α-methylbutyrate (p = 0.02). Six of eight SCFAs were significantly increased in F4 fibrosis. Conclusions: In the present study, SCFAs were associated with MASLD and fibrosis severity, but further research is needed to elucidate the potential mechanisms underlying our observations and to assess the possible benefit of therapies modulating gut microbiota.
KW - Acetate
KW - Butyrate
KW - Circulating SCFA
KW - Cirrhosis
KW - Metabolome
KW - Microbiome
KW - Non-alcoholic fatty liver disease
KW - Non-alcoholic steatohepatitis
KW - Propionate
KW - Targeted metabolomics
U2 - 10.1186/s12876-024-03129-7
DO - 10.1186/s12876-024-03129-7
M3 - Journal article
C2 - 38262952
AN - SCOPUS:85182858343
VL - 24
JO - B M C Gastroenterology
JF - B M C Gastroenterology
SN - 1471-230X
IS - 1
M1 - 43
ER -
ID: 381022928