Cholecystitis, or inflammation of the gallbladder, occurs due to gallstone production or blockages in the cystic ducts and causes severe pain (biliary colic) and fever, often requiring surgery. When bile flow is interrupted, a number of secondary problems such as fat-soluble vitamin malabsorption and liver damage can occur. Once the gallbladder is surgically removed, patients often encounter complications in the form of acute infections or chronic bowel difficulties that can last months or years, making gallbladder disease one of the most common and costly of all digestive diseases. Post-cholecystectomy Syndrome (PCS) arises from alterations in bile flow due to loss of the reservoir function of the gallbladder, and affects approximately 20-40% of patients. Although the exact reasons have not yet been elucidated, these complications are examples of a much wider problem – unknown effects of gallbladder removal on the human body’s biggest organ, its microbiome. Without the gallbladder, the body lacks a way of regulating the flow of bile into the intestines. It is expected that the increased bile flow leads to downstream changes in the intestinal population, but no such studies have been performed in humans.
Cholecystectomies rank number one for the most frequently performed major surgery. The National Health and Nutrition Examination Survey in the US estimated that 6.3 million men and 14.2 million women aged 20-74 yrs suffer gallbladder disease. The prevalence is 20 million cases among Europeans, whereby the incidence of gallstones is 1 million new cases/yr. In the US, direct and indirect costs of gallbladder disease represented a consumption of $6.2 billion in 2012, increasing by more than 20% over the last three decades. In 2013 England reported >12,000 cases of cholelithiasis, making it one of the primary reasons for hospital visits relating to gastrointestinal issues. Treatment is governed by non-specific diagnoses and usually includes pharmacologic or surgical approaches. As these number increase, considerable burden is placed on the healthcare system and taxpayer funds. However, the degree of research in this topic does not reflect demand, and much remains to be known about the epidemiology of gallbladder disease.
The MSCA-funded GallBiome project aimed to define the core gallbladder microbiome. It was hypothesized that measurable differences would be seen among the dominant phyla in healthy compared to diseased gallbladders and that removal of the gallbladder would lead to gut dysbiosis. To investigate these questions the fellow sought to achieve the following objectives: 1) mapping community changes linked to gallbladder disease; 2) quantifying changes in bacterial communities from gallbladder mucosa, bile, and stool as a function of time and patient status, 3) evaluations of gallbladder removal on the gut population (3) correlations among population profiles with metabolite profiles to glean microbial functions, and 4) the isolation and characterization of previously uncultivated anaerobic bacteria. Ultimately, this project seeks to understand the role of bacteria in gallbladder disease and will form the basis for establishing relationships between gallbladder microbiota and gut microbiota to benefit human health.
