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HFD aggravated the arthritis and atherosclerosis by altering the intestinal status and gut microbiota

Na Shi^1,2, Shan Jiang^1,2, Yue Zhao^1,2

¹Key Laboratory of Viral Pathogenesis and Infection Prevention and Control (Jinan University), Ministry of Education, School of Medicine, Jinan University, Guangzhou, 510632, China.

Molecular Medicine (Cambridge, Mass.)

|December 23, 2024

Insights

High-fat diets worsen rheumatoid arthritis (RA) and atherosclerosis in mice by disrupting gut microbiota and immune balance. This study highlights the link between diet, gut health, and chronic inflammatory diseases.

Area of Science:

Immunology
Cardiovascular Science
Microbiology

Background:

Rheumatoid arthritis (RA) and cardiovascular disease (CVD) are chronic inflammatory conditions.
The interplay between systemic inflammation in RA and atherosclerosis development is not fully understood.

Purpose of the Study:

To investigate the impact of a high-fat diet (HFD) on atherosclerosis development in a mouse model of arthritis.
To explore the effects of HFD on gut microbiota, intestinal homeostasis, and immune cell profiles.

Main Methods:

ApoE-/- mice were treated with K/BxN serum and a high-fat diet (HFD).
Phenotypic assessments included hyperlipidemia, atherosclerotic lesions, and arthropathy.
Immune profiles were analyzed, focusing on gut microbiota, intestinal barrier function, and immune cell populations (Th17/Treg balance, Peyer's patches, aortic leukocytes).

Main Results:

HFD exacerbated hyperlipidemia, atherosclerotic lesions, and arthritic symptoms in mice.
HFD significantly altered gut microbiota composition, impaired intestinal homeostasis, and shifted the Th17/Treg cell balance.
Decreased Peyer's patches, altered gut immune cell expression, and increased aortic leukocytes/macrophages were observed, indicating heightened inflammation.

Conclusions:

High-fat diet exacerbates both arthritis and atherosclerosis in ApoE-/- mice.
Diet-induced disruptions in microbiota, intestinal permeability, and immune homeostasis contribute to disease severity.
Findings suggest a mechanistic link between diet, gut dysbiosis, and the exacerbation of inflammatory diseases like RA and CVD.

Read full analysis

Abstract:

Rheumatoid arthritis (RA) and cardiovascular disease (CVD) are both the chronic inflammatory disease. To investigate the influence of secondary atherosclerosis on arthritis mice, we treated the ApoE^-/- mice with K/BxN serum and high fat diet (HFD), and subsequently assessed the phenotypes as well as immune profiles of K/BxN serum and HFD induced ApoE^-/- mice. We found that HFD treatment aggravated the hyperlipidemia, atherosclerotic lesions, ankle swelling and arthropathy of mice. We further demonstrated that HFD altered the gut microbiota and metabolism, intestinal homeostasis and Th17/Treg cell balance in lamina propria lymphocytes. Moreover, HFD decreased the number of Peyer' s patches and altered the expression profiling of gut immune cells. In addition, HFD increased the number of aortic leukocytes and macrophages, then aggravated the atherosclerosis in aorta, which led to greater inflammation in mice aorta and aortic root. Collectively, our study indicated that HFD aggravated the arthritis and atherosclerosis, which may be contributed by microbiota dysbiosis, the intestinal permeability and disrupted immunological homeostasis.

Keywords:

Arthritis combined with atherosclerosis Gut microbiota Inflammation Intestinal status

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