Journal of Cancer Research
- ISSN: 2578-3726
Alexandre Tavartkiladze, Gaiane Simonia, Ruite Lou, Pati Revazishvili, Maia Maisuradze, George Mamukashvili, Givi Zumbadze, Tamar Japaridze, Tatia Potskhoraia, Pirdara Nozadze, George Dundua and David Egiazarov
The COVID-19 pandemic has left an indelible mark on global health, with millions experiencing not only the acute effects of SARS-CoV-2 infection but also long-term sequelae collectively referred to as post-COVID syndrome or long COVID. Among its multifaceted impacts, the gastrointestinal system has emerged as a significant area of concern. This study explores the potential link between post-COVID syndrome and the development of small intestinal bacterial overgrowth (SIBO), focusing on mechanisms involving melatonin dysregulation, chronic inflammation, and dysbiosis. The findings suggest that post- COVID SIBO could represent a novel pre-cancerous condition, underscoring the urgent need for improved diagnostic and therapeutic strategies. An observational cohort study was conducted on 33 healthy individuals aged 17 to 69 years, who had no prior symptoms of SIBO before SARS-CoV-2 infection. Preventive baseline tests in 2019 included assessments of melatonin and melatonin sulfate levels, pro-inflammatory cytokines, stool analysis for dysbiosis, and tumor markers. In 2023, post-COVID, 18 participants developed SIBO symptoms, while 15 remained asymptomatic. The study revealed significant reductions in blood melatonin concentrations and 24-hour urinary melatonin sulfate levels across all participants (p <0.01). However, this reduction was more pronounced in the SIBO-positive group, accompanied by marked elevations in proinflammatory cytokines such as IL-6, TNF-α, IL-12, and IL-17. These findings highlight a strong inverse correlation between melatonin levels and inflammatory cytokines (r = -0.68, p < 0.01). Stool analyses indicated severe dysbiosis in SIBO-positive participants, characterized by an overgrowth of pathogenic bacteria and reduced microbial diversity. In contrast, SIBOnegative individuals exhibited only mild to moderate dysbiosis.
Notably, tumor markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19.9) were elevated in SIBO-positive individuals, raising concerns about potential early carcinogenic processes linked to chronic inflammation and microbial dysbiosis. No such elevations were observed in the SIBO-negative group. These findings suggest that SIBO, particularly in the context of post-COVID syndrome, may serve as a pre-cancerous condition necessitating early diagnosis and intervention. The study identifies several mechanisms potentially linking post-COVID syndrome to SIBO. Melatonin dysregulation, driven by post-COVID desynchronosis, appears to play a central role. As a regulator of circadian rhythms, melatonin impacts gastrointestinal motility, immune function, and gut microbiome composition. Reduced melatonin levels may impair gut motility, disrupt microbial balance, and exacerbate systemic inflammation, creating a conducive environment for bacterial overgrowth. Furthermore, chronic inflammation and increased intestinal permeability associated with dysbiosis amplify the risk of tumorigenesis, as evidenced by elevated tumor markers. This research highlights the clinical and research implications of post-COVID SIBO. Healthcare providers must remain vigilant for gastrointestinal symptoms in post-COVID patients and prioritize early diagnostic strategies, such as comprehensive breath tests, biomarker assessments, and stool analyses. Therapeutic interventions, including melatonin supplementation, probiotics, and targeted antimicrobial therapies, may mitigate the progression of SIBO and its associated complications. Additionally, the integration of advanced technologies, such as artificial intelligence and microbiome analysis, could revolutionize SIBO diagnostics and enhance precision medicine approaches. In conclusion, this study emphasizes the importance of recognizing post-COVID SIBO as a new and potentially pre-cancerous condition. By addressing melatonin dysregulation, chronic inflammation, and dysbiosis, healthcare providers can improve outcomes for millions of patients globally. Further research is essential to validate these findings and develop innovative strategies to prevent and treat SIBO, ultimately reducing its impact on global population health and mitigating the risks of cancer development.