Anti-TNF alpha treatment in Crohn's disease: Impact on hepatic steatosis, gut-derived hormones and metabolic status

Paul Manka; Svenja Sydor; Nishikant Wase; Jan Best; Malte Brandenburg; Annika Hellbeck; Julia Schanzer; Ramiro Vilchez-Vargas; Alexander Link; Anja Figge; Andreas Jahnert; Ulrike von Arnim; Jason D. Coombes; Francisco-Javier Cubero; Alisan Kahraman; Moon-Sung Kim; Julia Kalsch; Sonja Kinner; Klaas-Nico Faber; Han Moshage; Guido Gerken; Wing-Kin Syn; Scott L. Friedman; Ali Canbay; Lars P. Bechmann

doi:10.1111/liv.15003

Anti-TNF alpha treatment in Crohn's disease: Impact on hepatic steatosis, gut-derived hormones and metabolic status

Paul Manka, Svenja Sydor, Nishikant Wase, Jan Best, Malte Brandenburg, Annika Hellbeck, Julia Schanzer, Ramiro Vilchez-Vargas, Alexander Link, Anja Figge, Andreas Jahnert, Ulrike von Arnim, Jason D. Coombes, Francisco-Javier Cubero, Alisan Kahraman, Moon-Sung Kim, Julia Kalsch, Sonja Kinner, Klaas-Nico Faber, Han MoshageGuido Gerken, Wing-Kin Syn, Scott L. Friedman, Ali Canbay, Lars P. Bechmann^*

^*Corresponding author for this work

Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND AND AIMS: An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD-treatments are agents that inhibit Tumor-Necrosis-Factor (TNF) activity, yet it is unclear why anti-TNFα agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analyzed a potential relationship between anti-TNF treatment and hepatic steatosis in CD, focusing on the gut-liver axis.

METHODS: This cross-sectional study evaluated patients with established CD, with and without anti-TNFα treatment, analyzing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP), and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analyzed gut microbiota composition and mediators of bile acid (BA) signaling via stool and serum analysis.

RESULTS: Patients on anti-TNFα treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti-TNFα therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti-TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group-specific alterations with low levels in patients without anti-TNFα treatment. Low abundance of Firmicutes was associated with higher triglyceride levels.

CONCLUSIONS: Anti-TNFα treatment is associated with reduced steatosis, lower triglyceride levels, alterarions in FXR-signaling (e.g., FGF19) and microbiota composition in CD.

Original language	English
Pages (from-to)	2646-2658
Number of pages	13
Journal	Liver International
Volume	41
Issue number	11
DOIs	https://doi.org/10.1111/liv.15003
Publication status	Published - Nov-2021

Keywords

Crohn's disease
microbiota
steatosis
TNF-alpha
NECROSIS-FACTOR-ALPHA
NONALCOHOLIC STEATOHEPATITIS
BILE-ACIDS
LIVER
MICROBIOME
EXPRESSION
GLP-1
INFLAMMATION
REGULATORS
INCRETINS

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Anti‐TNFα treatment in Crohn’s disease_ Impact on hepatic steatosis, gut‐derived hormones and metabolic statusFinal publisher's version, 1.71 MBLicence: CC BY

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Manka, P., Sydor, S., Wase, N., Best, J., Brandenburg, M., Hellbeck, A., Schanzer, J., Vilchez-Vargas, R., Link, A., Figge, A., Jahnert, A., von Arnim, U., Coombes, J. D., Cubero, F.-J., Kahraman, A., Kim, M.-S., Kalsch, J., Kinner, S., Faber, K.-N., ... Bechmann, L. P. (2021). Anti-TNF alpha treatment in Crohn's disease: Impact on hepatic steatosis, gut-derived hormones and metabolic status. Liver International, 41(11), 2646-2658. https://doi.org/10.1111/liv.15003

@article{e794c0997580403990c6a5fa48f36567,

title = "Anti-TNF alpha treatment in Crohn's disease: Impact on hepatic steatosis, gut-derived hormones and metabolic status",

abstract = "BACKGROUND AND AIMS: An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD-treatments are agents that inhibit Tumor-Necrosis-Factor (TNF) activity, yet it is unclear why anti-TNFα agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analyzed a potential relationship between anti-TNF treatment and hepatic steatosis in CD, focusing on the gut-liver axis.METHODS: This cross-sectional study evaluated patients with established CD, with and without anti-TNFα treatment, analyzing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP), and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analyzed gut microbiota composition and mediators of bile acid (BA) signaling via stool and serum analysis.RESULTS: Patients on anti-TNFα treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti-TNFα therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti-TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group-specific alterations with low levels in patients without anti-TNFα treatment. Low abundance of Firmicutes was associated with higher triglyceride levels.CONCLUSIONS: Anti-TNFα treatment is associated with reduced steatosis, lower triglyceride levels, alterarions in FXR-signaling (e.g., FGF19) and microbiota composition in CD.",

keywords = "Crohn's disease, microbiota, steatosis, TNF-alpha, NECROSIS-FACTOR-ALPHA, NONALCOHOLIC STEATOHEPATITIS, BILE-ACIDS, LIVER, MICROBIOME, EXPRESSION, GLP-1, INFLAMMATION, REGULATORS, INCRETINS",

author = "Paul Manka and Svenja Sydor and Nishikant Wase and Jan Best and Malte Brandenburg and Annika Hellbeck and Julia Schanzer and Ramiro Vilchez-Vargas and Alexander Link and Anja Figge and Andreas Jahnert and {von Arnim}, Ulrike and Coombes, {Jason D.} and Francisco-Javier Cubero and Alisan Kahraman and Moon-Sung Kim and Julia Kalsch and Sonja Kinner and Klaas-Nico Faber and Han Moshage and Guido Gerken and Wing-Kin Syn and Friedman, {Scott L.} and Ali Canbay and Bechmann, {Lars P.}",

year = "2021",

month = nov,

doi = "10.1111/liv.15003",

language = "English",

volume = "41",

pages = "2646--2658",

journal = "Liver International",

issn = "1478-3223",

publisher = "Wiley",

number = "11",

}

Manka, P, Sydor, S, Wase, N, Best, J, Brandenburg, M, Hellbeck, A, Schanzer, J, Vilchez-Vargas, R, Link, A, Figge, A, Jahnert, A, von Arnim, U, Coombes, JD, Cubero, F-J, Kahraman, A, Kim, M-S, Kalsch, J, Kinner, S, Faber, K-N , Moshage, H, Gerken, G, Syn, W-K, Friedman, SL, Canbay, A & Bechmann, LP 2021, 'Anti-TNF alpha treatment in Crohn's disease: Impact on hepatic steatosis, gut-derived hormones and metabolic status', Liver International, vol. 41, no. 11, pp. 2646-2658. https://doi.org/10.1111/liv.15003

TY - JOUR

T1 - Anti-TNF alpha treatment in Crohn's disease

T2 - Impact on hepatic steatosis, gut-derived hormones and metabolic status

AU - Manka, Paul

AU - Sydor, Svenja

AU - Wase, Nishikant

AU - Best, Jan

AU - Brandenburg, Malte

AU - Hellbeck, Annika

AU - Schanzer, Julia

AU - Vilchez-Vargas, Ramiro

AU - Link, Alexander

AU - Figge, Anja

AU - Jahnert, Andreas

AU - von Arnim, Ulrike

AU - Coombes, Jason D.

AU - Cubero, Francisco-Javier

AU - Kahraman, Alisan

AU - Kim, Moon-Sung

AU - Kalsch, Julia

AU - Kinner, Sonja

AU - Faber, Klaas-Nico

AU - Moshage, Han

AU - Gerken, Guido

AU - Syn, Wing-Kin

AU - Friedman, Scott L.

AU - Canbay, Ali

AU - Bechmann, Lars P.

PY - 2021/11

Y1 - 2021/11

N2 - BACKGROUND AND AIMS: An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD-treatments are agents that inhibit Tumor-Necrosis-Factor (TNF) activity, yet it is unclear why anti-TNFα agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analyzed a potential relationship between anti-TNF treatment and hepatic steatosis in CD, focusing on the gut-liver axis.METHODS: This cross-sectional study evaluated patients with established CD, with and without anti-TNFα treatment, analyzing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP), and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analyzed gut microbiota composition and mediators of bile acid (BA) signaling via stool and serum analysis.RESULTS: Patients on anti-TNFα treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti-TNFα therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti-TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group-specific alterations with low levels in patients without anti-TNFα treatment. Low abundance of Firmicutes was associated with higher triglyceride levels.CONCLUSIONS: Anti-TNFα treatment is associated with reduced steatosis, lower triglyceride levels, alterarions in FXR-signaling (e.g., FGF19) and microbiota composition in CD.

AB - BACKGROUND AND AIMS: An association between Crohn's disease (CD) and hepatic steatosis has been reported. However, the underlying mechanisms of steatosis progression in CD are not clear. Among the most effective CD-treatments are agents that inhibit Tumor-Necrosis-Factor (TNF) activity, yet it is unclear why anti-TNFα agents would affect steatosis in CD. Recent studies suggest that microbiome can affect both, CD and steatosis pathogenesis. Therefore, we here analyzed a potential relationship between anti-TNF treatment and hepatic steatosis in CD, focusing on the gut-liver axis.METHODS: This cross-sectional study evaluated patients with established CD, with and without anti-TNFα treatment, analyzing serum markers of liver injury, measurement of transient elastography, controlled attenuation parameter (CAP), and MRI for fat detection. Changes in lipid and metabolic profiles were assessed by serum and stool lipidomics and metabolimics. Additionally, we analyzed gut microbiota composition and mediators of bile acid (BA) signaling via stool and serum analysis.RESULTS: Patients on anti-TNFα treatment had less hepatic steatosis as assessed by CAP and MRI. Serum FGF19 levels were significantly higher in patients on anti-TNFα therapy and associate with reduced steatosis and increased bowel motility. Neutral lipids including triglycerides were reduced in the serum of patients on anti-TNF treatment. Bacteria involved in BA metabolism and FGF19 regulation, including Firmicutes, showed group-specific alterations with low levels in patients without anti-TNFα treatment. Low abundance of Firmicutes was associated with higher triglyceride levels.CONCLUSIONS: Anti-TNFα treatment is associated with reduced steatosis, lower triglyceride levels, alterarions in FXR-signaling (e.g., FGF19) and microbiota composition in CD.

KW - Crohn's disease

KW - microbiota

KW - steatosis

KW - TNF-alpha

KW - NECROSIS-FACTOR-ALPHA

KW - NONALCOHOLIC STEATOHEPATITIS

KW - BILE-ACIDS

KW - LIVER

KW - MICROBIOME

KW - EXPRESSION

KW - GLP-1

KW - INFLAMMATION

KW - REGULATORS

KW - INCRETINS

U2 - 10.1111/liv.15003

DO - 10.1111/liv.15003

M3 - Article

C2 - 34219348

SN - 1478-3223

VL - 41

SP - 2646

EP - 2658

JO - Liver International

JF - Liver International

IS - 11

ER -

Anti-TNF alpha treatment in Crohn's disease: Impact on hepatic steatosis, gut-derived hormones and metabolic status

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Keywords

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