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Microbes & Immunity

ORIGINAL RESEARCH ARTICLE
Modulation of host immune response by

carotene supplementation in a COVID-19
vaccination mouse model

Kang Wei Tan , Saatheeyavaane Bhuvanendran , Kar Wai Hong ,
Uma Devi Palanisamy , and Ammu Kutty Radhakrishnan*
Food as Medicine Research Strength, Jeffrey Cheah School of Medicine and Health Sciences,
Monash University Malaysia, Selangor, Malaysia

Abstract
Carotenoids, known for their immunomodulatory and gut microbiota-modulating
effects, have drawn attention as potential dietary adjuvants to enhance vaccine
efficacy and maintain gut health. This study aimed to evaluate the effect of carotene
supplementation on immune response with insight into gut microbiome using an
in vivo animal model. The BALB/c mice were fed daily with CaroGaia (50 mg/kg of
body weight), a carotene supplement that contained 33.3% α-carotene and 66.6%
β-carotene, by oral gavage for 70 days. Mice fed with the vehicle served as controls.
The mice in the vaccinated groups received two doses of the CoronaVac inactivated
virus vaccine on days 14 and 42. Flow cytometry revealed no significant modulation
*Corresponding author: of lymphocyte subsets (total T lymphocytes, T-helper cells, cytotoxic T lymphocytes,
Ammu Kutty Radhakrishnan
(ammu.radhakrishnan@monash. and B cells) with carotene supplementation. In addition, there were no significant
edu) differences in the levels of SARS-CoV-2 immunoglobulin G and interferon-gamma in
Citation: Tan KW, Bhuvanendran S, plasma between treatment and control groups. In contrast, the vaccinated carotene
Hong KW, Palanisamy UD, group showed an increased SARS-CoV-2 antigen-specific splenocyte proliferation. In
Radhakrishnan AK. Modulation of the gut microbiome, carotene supplementation appeared to alter the gut microbiota
host immune response by carotene
supplementation in a COVID-19 composition. However, no significant changes were observed in the short-chain fatty
vaccination mouse model. Microbes acids (SCFA) levels, such as acetic acid, butyric acid, and propionic acid. Furthermore,
& Immunity. 2025;2(3):72-86. the differential abundance analysis showed that carotene supplementation reduced
doi: 10.36922/MI025110021
the levels of SCFA producers (Odoribacter and Monoglobus genera) in unvaccinated
Received: March 10, 2025 mice compared to the control group, while it enriched the level of SCFA producers
Revised: April 8, 2025 (Ruminococcaceae family) and reduced pathobiont levels, commensal bacteria that
have pathogenic potential (Mucispirillum genus), in the vaccinated group.
Accepted: April 21, 2025
Published online: May 15, 2025
Keywords: COVID-19; SARS-CoV-2; Vaccination; Carotenoid; Carotene; Immune-
Copyright: © 2025 Author(s). modulation; Gut microbiota; Short-chain fatty acid
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium, 1. Introduction
provided the original work is
properly cited. The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory
Publisher’s Note: AccScience syndrome coronavirus 2 (SARS-CoV-2), emerged in China in late 2019. By March
1
Publishing remains neutral with 2020, the World Health Organization had declared it a pandemic. The virus rapidly
regard to jurisdictional claims in
published maps and institutional spread worldwide, causing severe disruptions to societies, economies, and politics. The
affiliations. pandemic had led to millions of infections and deaths without signs of abating. Given

Volume 2 Issue 3 (2025) 72 doi: 10.36922/MI025110021