Liver diseases, accounting for about 2 million deaths worldwide, are known for their complexity. Among the different types, non-alcoholic fatty liver disease (NAFLD) is particularly prevalent, affecting around 30% of the global population. There is a need of urgent comprehensive strategies to address all aspects of diagnosis and management of this condition. 

A recent study led by Partha Chakrabarti at CSIR-Indian Institute of Chemical Biology (IICB), Kolkata, explores the therapeutic potential of the microorganisms colonising the human gut, commonly known as the ​‘gut microbiota,’ as a preventive strategy for NAFLD. ​“We wanted to seek the ​‘drugs from the bugs’,” says Chakrabarti, ​“to pave new preventive as well as therapeutic avenues”.

NAFLD is an umbrella term for a range of diseases characterised by accumulation of excess fat in the liver, and not caused by alcohol consumption, hence termed as ​‘non-alcoholic’. Sachin Palnitkar, an honorary consultant and liver transplant physician, Deenanath Mangeshkar Hospital, Pune says, ​“It is highly prevalent among Asian populations and remains asymptomatic until it progresses to cirrhosis or hepatocellular carcinoma. Once the disease is diagnosed, it becomes irreversible”. 

NAFLD begins with harmless accumulation of fat in the liver, known as steatosis. But it can progress to a condition called non-alcoholic steatohepatitis (NASH), characterised by liver inflammation. Ultimately, NAFLD can progress to a more serious condition called cirrhosis, putting individuals at a heightened risk of developing various other serious health problems.

The human gut consists of trillions of bacteria, and variations in their composition and function, known as gut dysbiosis, are associated with several disease conditions. The gut microbiota releases various metabolic compounds that interact with our cells and reach the liver through the portal circulation, playing a role in the liver’s immunologic environment. Butyrate, one such metabolite and a short chain fatty acid, has shown potential in reducing inflammation in numerous diseases. 

Ankita Sarkar, the first author of the study, explains, ​“We investigated how butyrate can affect the progression of NAFLD using mice that were fed a specific diet to induce NAFLD. Our findings show that butyrate is effective in reducing inflammation in macrophages found in the liver”. This research focused on studying the effects of butyrate on the immune system and its impact on liver health using animal models.

“I would like to congratulate the authors on this well-executed study. I believe this research provides valuable insights into the underlying mechanisms of NASH, emphasising the role of macrophage sub-populations and suggesting a potential target for treating inflammation-related liver damage in NASH,” says Pragyan Acharya, All India Institute of Medical Science (AIIMS) Delhi, an additional professor specialising in liver disease. 

In their findings, Sarkar et​.al., observed a notable decrease in the number of inflammatory immune cells and the elimination of sub-groups of macrophages that cause inflammation. These findings are noteworthy because immune cells infiltrating the liver play a critical role in driving the progression of the disease, and macrophages are among the immune cells that multiply and become active during inflammation.

Chakrabarti says, ​“We also aim to study how butyrate affects other metabolic problems and its role in the connection between the gut and the brain by regulating the feeding centre of the hypothalamus”. He further adds ​“Fecal transplantation from healthy individuals to obese patients, which encourages the growth of bacteria that produce butyrate called Roseburia intestinalis, can potentially modulate the gut-microbial ecology or improve the clinical outlook for NAFLD”.

“This research will significantly expand the scope of early interventions in NASH,” adds Palnitkar.