Radiocarbon Dating of Gallstones for Timeline of Formation, Dormancy Analysis, and Correlation with Chemical/Microbial Composition: A Pilot Study on Gallstone Geobiology

Vipin Yadav; Ragini Kilambi; Rajveer Sharma; Nihar Mohaptra; Shridhar V Sasturkar; Anit Dawar; Archana Rastogi; Manju Saini; Deepti Sharma; Nirupama Trehanpati; Pratibha R Kale; Viniyendra Pamecha; Gayatri Ramakrishna

doi:10.1016/j.gassur.2024.101937

Radiocarbon Dating of Gallstones for Timeline of Formation, Dormancy Analysis, and Correlation with Chemical/Microbial Composition: A Pilot Study on Gallstone Geobiology

J Gastrointest Surg. 2024 Dec 26:101937. doi: 10.1016/j.gassur.2024.101937. Online ahead of print.

Affiliations

¹ Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, Delhi, India.
² Department of Hepatopancreatobiliary Surgery, Institute of Liver and Biliary Sciences, Delhi, India.
³ Inter-University Accelerator Centre, Delhi, India.
⁴ Department of Histopathology, Institute of Liver and Biliary Sciences, Delhi, India.
⁵ Amity Stem Cell Institute, Amity Medical School, Amity University Haryana, Panchgaon, Manesar (Gurugram), Haryana, India.
⁶ Department of Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India.
⁷ Department of Microbiology, Institute of Liver and Biliary Sciences, Delhi, India.
⁸ Department of Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India. Electronic address: [email protected].

PMID: 39732159
DOI: 10.1016/j.gassur.2024.101937

Abstract

Background: India has a high incidence of gallstones, which can cause chronic inflammation and increase the risk of gallbladder cancer. Understanding the age and composition of gallstones can provide insights into their formation and growth. This study used ¹⁴C dating, FTIR, and metagenome analysis to explore the natural history, deposition rate, and microbial/chemical composition of gallstones.

Method: In this pilot study three cholesterol gallstones were chosen with different tissue histopathologies (normal, metaplasia, and dysplasia) and respective layers were analyzed for ¹⁴C bomb pulse dating and FTIR for age and chemical composition respectively. The core of each gallstone was subjected to scanning electron microscopy and further to 16S rRNA sequencing for microbial analysis.

Result: The ¹⁴C data indicated that the largest stone with dysplastic epithelium formed over a period of six years, while stones with metaplasia and normal pathology took 13 and 12 years, to develop, respectively. Further, the largest stone was dormant for 6 years before subject experienced acute pain, while other two stones laid dormant for 7 and 18 years. FTIR analysis revealed that all the three gallstones were primarily composed of cholesterol. Additionally, calcium oxalate, calcium carbonate, and calcium bilirubinate were present in stones with underlying dysplasia. The 16S rRNA analysis showed an increased abundance of Corynebacterium sp. in stones associated with metaplasia and dysplasia. Moreover, pathogenic species of Klebsiella and E. coli were abundant in calcium oxalate-rich gallstones with underlying dysplasia.

Conclusion: Overall, the pilot study established the feasibility of ¹⁴C bomb pulse in evaluating the timeline of gallstone formation and combining with FTIR/metagenome analysis helps in understanding the natural history of gallstone associated disease.

Keywords: Carbon Dating ((14)C); Fourier Transform Infrared Spectroscopy (FTIR); Fraction Modern Carbon (PMC); Gallstone; Metagenome; Scanning Electron Microscopy (SEM).