Beyond BMI: The Synergistic Effect of Ultra-Processed Food Consumption and Sedentary Behavior on Gut Microbiota and Systemic Inflammation in Young Adults with Early Metabolic Syndrome – A Longitudinal Cohort Study
Article Sidebar
Main Article Content
Abstract
Background: Body mass index (BMI) inadequately captures metabolic risks driven by modern lifestyles, particularly the combination of ultra-processed food (UPF) intake and sedentary behavior. While each factor independently fosters low-grade systemic inflammation, their synergistic impact on the gut microbiota–inflammation axis in young adults with early metabolic syndrome (MetS) remains unexplored. Objective: This longitudinal cohort study examined the independent and synergistic effects of UPF consumption and sedentary behavior on gut microbiota composition and systemic inflammatory biomarkers in Indonesian young adults with early MetS over 12 months. Methods: We recruited 400 participants aged 20–30 years meeting 1–2 ATP III criteria for MetS. Dietary intake was assessed with a validated semi-quantitative FFQ with NOVA classification; sedentary time was measured via triaxial accelerometers. Gut microbiota was profiled using 16S rRNA sequencing (V3–V4 region), and hs-CRP, IL-6, and TNF-α were quantified at baseline and 12 months. Participants were stratified into four groups by median splits of UPF energy share (%kcal) and daily sedentary time. Generalized estimating equations tested synergistic interactions on inflammation, and mediation analyses evaluated microbiota diversity pathways. Results: The high-UPF/high-sedentary group exhibited the greatest increases in hs-CRP (+1.78 mg/L), IL-6 (+2.95 pg/mL), and TNF-α (+3.12 pg/mL), with a significant multiplicative interaction (p<0.001). Shannon diversity declined most sharply in the high-UPF/high-sedentary group (−0.32), paralleled by a rise in the Firmicutes/Bacteroidetes ratio (+0.47). Mediation analysis showed that 31.4% of the synergistic effect on hs-CRP was mediated by loss of diversity. Conclusion: Co-occurring high UPF consumption and sedentary behavior synergistically amplify systemic inflammation partly through gut dysbiosis in early MetS, underscoring the need to target both dietary and physical activity domains beyond BMI-centric strategies
Downloads
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
K. Erdoğan and N. Sanlier, “Metabolic Syndrome and Menopause: The Impact of Menopause Duration on Risk Factors and Components,” Int. J. Womens. Health, vol. Volume 16, pp. 1249–1256, Jul. 2024, doi: 10.2147/IJWH.S460645.
R. K. Morris, E. Johnstone, C. Lees, V. Morton, and G. Smith, “Investigation and Care of a Small‐for‐Gestational‐Age Fetus and a Growth Restricted Fetus (Green‐top Guideline No. 31),” BJOG An Int. J. Obstet. Gynaecol., vol. 131, no. 9, Aug. 2024, doi: 10.1111/1471-0528.17814.
E. Y. Bachtiar, R. G. H. Novika, B. Murti, E. P. Pamungkasari, and S. S. Rahardjo, “Determinants of Low Birth Weight at Dr. Moewardi Hospital, Surakarta, Central Java, Indonesia,” J. Matern. Child Heal., vol. 10, no. 6, pp. 383–398, 2025, doi: 10.26911/thejmch.2025.10.06.05.
K. Ryczkowska, W. Adach, K. Janikowski, M. Banach, and A. Bielecka-Dabrowa, “Menopause and women’s cardiovascular health: is it really an obvious relationship?,” Arch. Med. Sci., vol. 19, no. 2, pp. 458–466, Mar. 2023, doi: 10.5114/aoms/157308.
T. E. Cook, A. T. Tyra, R. C. Brindle, and A. T. Ginty, “The Relationship Between Subjective Sleep, Biological Sex, and Cardiovascular and Psychological Reactivity to Acute Psychological Stress,” Psychophysiology, vol. 63, no. 1, Jan. 2026, doi: 10.1111/psyp.70213.
J. Kachimba, C. M. Ngoma, and C. Kwaleyela, “Exploring Adolescent Mothers’ Experiences of Social and Behavioral Change Communication Interventions for Safe Motherhood in Ndola District, Zambia,” Br. J. Healthc. Med. Res., vol. 12, no. 05, pp. 138–150, Nov. 2025, doi: 10.14738/bjhr.1205.19518.
X. Zhang, “Distinct Neurobiological Mechanisms of Chronic and Acute Stress in Major Depressive Disorder: A Review,” Lect. Notes Educ. Psychol. Public Media, vol. 113, no. 1, pp. 149–154, Sep. 2025, doi: 10.54254/2753-7048/2025.NS26871.
J. Lu et al., “Study on the Zinc Nutritional Status and Risk Factors of Chinese 6–18-Year-Old Children,” Nutrients, vol. 15, no. 7, p. 1685, Mar. 2023, doi: 10.3390/nu15071685.
M. Zinöcker and I. Lindseth, “The Western Diet–Microbiome-Host Interaction and Its Role in Metabolic Disease,” Nutrients, vol. 10, no. 3, p. 365, Mar. 2018, doi: 10.3390/nu10030365.
Clayton A. Copeland, C. Tobin, and Linda Lucas Walling, “Breaking Reading Barriers for Children with Disabilities,” Proc. ALISE Annu. Conf., Oct. 2025, doi: 10.21900/j.alise.2025.2037.
S. Sarkar, A. S. Abeyagunawardena, and R. Sinha, “Impact of glucocorticoid therapy on hypothalamic-pituitary-adrenal axis function in pediatric nephrotic syndrome: A narrative review,” World J. Clin. Pediatr., vol. 14, no. 4, Dec. 2025, doi: 10.5409/wjcp.v14.i4.110374.
D. Dhanyalayam, H. Thangavel, K. Lizardo, J. V. Desai, and J. F. Nagajyothi, “Sex-specific transcriptional regulation in lung macrophages during sub-acute Mycobacterium tuberculosis infection,” Microbiol. Spectr., vol. 13, no. 12, Dec. 2025, doi: 10.1128/spectrum.01790-25.
G. Pagliai, M. Dinu, M. P. Madarena, M. Bonaccio, L. Iacoviello, and F. Sofi, “Consumption of ultra-processed foods and health status: a systematic review and meta-analysis,” Br. J. Nutr., vol. 125, no. 3, pp. 308–318, Feb. 2021, doi: 10.1017/S0007114520002688.
G.-B. van Setten, “Ocular Surface Allostasis—When Homeostasis Is Lost: Challenging Coping Potential, Stress Tolerance, and Resilience,” Biomolecules, vol. 13, no. 8, p. 1246, Aug. 2023, doi: 10.3390/biom13081246.
Z. Song et al., “Mechanics‐Resilient HA/SIS‐Based Composite Scaffolds with ROS‐Scavenging and Bacteria‐Resistant Capacity to Address Infected Bone Regeneration,” Adv. Funct. Mater., vol. 34, no. 24, Jun. 2024, doi: 10.1002/adfm.202315382.
L. J. Mailing, J. M. Allen, T. W. Buford, C. J. Fields, and J. A. Woods, “Exercise and the Gut Microbiome: A Review of the Evidence, Potential Mechanisms, and Implications for Human Health,” Exerc. Sport Sci. Rev., vol. 47, no. 2, pp. 75–85, Apr. 2019, doi: 10.1249/JES.0000000000000183.
R. M. Chandika, “Generalizability and Consistency of Derived Dietary Patterns across Gender and Residence Subgroups among University Students, Saudi Arabia,” Saudi J. Heal. Res. Pract., vol. 1, no. 3 & 4, pp. 1–6, Oct. 2025, doi: 10.63908/ck4v7h88.
A. Ambrogi, V. Panetta, S. Folcarelli, M. Piras, M. Diomedi, and I. Maestrini, “Comparative Analysis of Antithrombotic Strategies in Atrial Fibrillation Patients with Ischemic Stroke: A Propensity Score and Inverse Probability Weighting Approach with three groups,” Epidemiol. Biostat. Public Heal., Sep. 2025, doi: 10.54103/2282-0930/29288.
Z. Shaheen, M. S. Ullah, S. Imran, N. Akram, M. Alorini, and U. Sarwar, “Clinical Correlation between Cervical Cancer Screening Using Pap Smear Test,” Pakistan J. Med. Heal. Sci., vol. 16, no. 7, pp. 900–902, Jul. 2022, doi: 10.53350/pjmhs22167900.
C. Zhu, T. Zhang, Q. Li, X. Chen, and K. Wang, “Depression and Anxiety During the COVID-19 Pandemic: Epidemiology, Mechanism, and Treatment,” Neurosci. Bull., vol. 39, no. 4, pp. 675–684, Apr. 2023, doi: 10.1007/s12264-022-00970-2.
A. B. Lloyd and G. Havenith, “Reply to Richalet and Hermand. Updating the CVR model for limitations in maximum myocardial contractility at high altitude,” J. Appl. Physiol., vol. 134, no. 1, pp. 148–149, Jan. 2023, doi: 10.1152/japplphysiol.00678.2022.
J. Spittler and L. Oberle, “Current Trends in Ultramarathon Running,” Curr. Sports Med. Rep., vol. 18, no. 11, pp. 387–393, Nov. 2019, doi: 10.1249/JSR.0000000000000654.
T. Langfield, L. Marty, M. Inns, A. Jones, and E. Robinson, “Healthier diets for all? A systematic review and meta‐analysis examining socioeconomic equity of the effect of increasing availability of healthier foods on food choice and energy intake,” Obes. Rev., vol. 24, no. 6, Jun. 2023, doi: 10.1111/obr.13565.
X. Sun et al., “Intermittent compared with continuous calorie restriction for treatment of metabolic dysfunction-associated steatotic liver disease: a randomized clinical trial,” Am. J. Clin. Nutr., vol. 121, no. 1, pp. 158–166, Jan. 2025, doi: 10.1016/j.ajcnut.2024.10.012.
J. Lyon, M. Connell, K. Chandrasekaran, and S. Srivastava, “Effect of synbiotics on weight loss and metabolic health in adults with overweight and obesity: A randomized controlled trial,” Obesity, vol. 31, no. 8, pp. 2009–2020, Aug. 2023, doi: 10.1002/oby.23801.
J. E. Finnell and C. R. Ferrario, “Applying behavioral economics-based approaches to examine the effects of liquid sucrose consumption on motivation,” Appetite, vol. 186, p. 106556, Jul. 2023, doi: 10.1016/j.appet.2023.106556.