Photo credit: www.sciencedaily.com

New Insights on the Microbiome’s Role in Cirrhosis and Antibiotic Resistance

Recent research reveals significant correlations between bacterial changes in the microbiome and rising antibiotic resistance, underscoring the necessity for more precise antibiotic treatment strategies.

This pioneering study offers a thorough examination of the similarities between bacterial populations in the oral cavity and the gut. It also investigates the conditions that enable harmful bacteria to thrive as cirrhosis advances.

The human microbiome, composed of complex bacterial communities, undergoes significant alterations in cirrhosis—a condition defined by the replacement of healthy liver tissue with scar tissue, which impairs liver function. While there is currently no cure for cirrhosis, the disease adversely impacts quality of life, shortens life expectancy, and may necessitate a liver transplant, a procedure not suitable for all patients. In the UK alone, cirrhosis accounts for more than 10,000 deaths annually, with liver disease imposing a burden of over £2 billion on the National Health Service (NHS).

Infection is a pivotal factor contributing to complications and mortality associated with cirrhosis. Growing evidence suggests that alterations in the microbiome—both in the gut and oral cavity—play a significant role in these infections. This hypothesis has been explored in a collaborative study led by researchers from King’s College London, the Roger Williams Institute of Liver Studies, and King’s College Hospital.

Rising Levels of Harmful Bacteria

Employing cutting-edge DNA sequencing technology, researchers found that individuals with varying stages of cirrhosis exhibited higher concentrations of harmful bacteria and diminished populations of beneficial bacteria. As the severity of cirrhosis increased, so did the prevalence of harmful bacteria possessing ‘virulence factors’ that enable their survival and proliferation in affected individuals.

Transfer of Bacteria Between Mouth and Gut

Furthermore, the study indicated that the distinction between the mouth and gut microbiomes diminished in cirrhosis patients. In healthy individuals, significant variation is observed in bacterial colonies between these sites. The convergence of bacteria from the mouth to the gut—and potentially the reverse—may contribute to disruptions in essential gut functions and the integrity of the gut wall. Notably, as cirrhosis progresses, the overlap of bacterial populations in the two regions becomes more pronounced.

Antimicrobial Resistance and the Implications for Treatment

A critical finding of the study is that advanced cirrhosis patients harbor bacteria with an increased number of genes associated with antibiotic resistance. This presents a pressing challenge to treatment efficacy. Typically, when individuals with cirrhosis are hospitalized, they are often administered broad-spectrum antibiotics as a precaution, even in the absence of confirmed infections. Given that untreated infections can elevate mortality risk by 10% for each hour of delay in antibiotic intervention, this practice is concerning.

However, indiscriminate antibiotic use can exacerbate microbiome imbalances, leading to heightened resistance among bacteria without necessarily resolving the underlying infection. This scenario accentuates the urgent need for improved diagnostic techniques to accurately identify infections and tailor antibiotic treatments accordingly.

Researchers at King’s College London collaborated on the analysis involving 100 patients, encompassing cases of mild to severe cirrhosis, in comparison to healthy individuals.

Expert Perspectives

Dr. Vishal Patel, a Reader in Hepatology at the Roger Williams Institute, stated, “This research emphasizes the crucial role of microbiome changes in accelerating cirrhosis, particularly as multidrug-resistant infections become increasingly prevalent. Our findings indicate a close relationship between bacterial overlap, virulence, and resistance genes with clinical outcomes, particularly among patients with advanced cirrhosis.”

He added, “These insights point toward the potential for personalized, microbiome-focused treatments to enhance outcomes for individuals with chronic liver disease, alongside initiatives to improve oral health. Moreover, this work highlights the necessity for rapid and precise infection diagnostics in cirrhosis patients to optimize existing antibiotic therapies.”

Co-author Dr. Saeed Shoaie emphasized the impact of their findings in tracing antibiotic-resistant bacteria through oral-gut microbiome analyses, which could aid in refining diagnosis, surveillance, and personalized treatment regimens. He noted, “This approach could integrate with artificial intelligence (AI) to discern key resistance patterns, facilitating targeted antibiotic interventions.”

Professor Philip Newsome, Director of the Roger Williams Institute of Liver Studies, remarked, “This study brings us closer to individualized treatment strategies for chronic liver disease, suggesting that manipulating the microbiome could provide new avenues for therapeutic development.”

References:

1 British Liver Trust – https://britishlivertrust.org.uk/information-and-support/statistics/

2 The Lancet – https://pubmed.ncbi.nlm.nih.gov/27989558/

3 National Institute of Health (NIH) – https://pmc.ncbi.nlm.nih.gov/articles/PMC3556696/

Source
www.sciencedaily.com