A novel probiotic mixture may offer potential therapeutic effects on hepatocelluar carcinoma

Researchers at the University of Hong Kong, in collaboration with the University of Eastern Finland, found a reduction of the tumor weight and size by 40% following feeding a mouse model with a novel probiotic mixture, “Prohep”, 1 week before the tumor inoculation.

Hepatocellular carcinoma (HCC) is an aggressive tumor with sobering prognosis. The major shortcoming related to current HCC treatment is the high health-care cost. For example, molecular targeted therapy using sorafenib as recommended by NCCN/AASLD/JSH/ESMO Guideline is expensive, with an average cost around US$6 000 per month, so it can only be performed in countries with extensive financial resources for healthcare services. Published cost analysis of HCC in the United States indicated that the mean 5-year net costs is∼US$45,000 for an average HCC patient per month.

Meanwhile, probiotics, bacterial cocktails, may be commonly found in dairy food products, and the cost is only ~US$86.00 per month for buying patented commercial products such as VSL#3. Microbiome-based therapeutics may therefore offer a cheaper approach in HCC intervention.

Key research findings

Cancer progression is a very complex process. In many cancers, there is a marked infiltration of the tumour microenvironment by different types of immune cells, such as T cells, neutrophils, natural killer cells, macrophages, and myeloid-derived suppressor cells. T helper 17 (Th17) cells are a subset of the T-cell population and their prevalence in the tumour microenvironment has been previously reported to increase during tumour progression. These Th17 cells are producing cytokines that enhance angiogenesis, a very important process in cancer progression. Tumour-associated inflammation is also unfavourable for the host and inflammatory cells have been found to be present in the tumour microenvironment of most tumours playing a pivotal role in the tumour promoting direction by escalating tumour angiogenesis and cell growth. Especially in hepatocellular carcinoma (HCC), a highly vascularized tumour, new vasculature is necessary for supplying nutrients and oxygen to support the growth of tumour cells, therefore modulating these two highly linked processes, inflammation and angiogenesis, could be proven an excellent strategy to control HCC growth. 

The biochemical analysis carried out in the study indicated that the probiotics’ beneficial effect is closely related with the weakened angiogenesis and reduced Th17 cells recruited from the intestine. The metagenome sequencing revealed that the reduced recruitment of Th17 cells was correlated with the probiotics’ modulated gut microbiota. Furthermore the abundance of certain beneficial bacteria that produce anti-inflammatory metabolites was increased upon probiotics administration.

“Of course there are many more parameters that need to be elucidated in relation to our study, and we are already working on improving the bacterial mixture to create even more efficient cocktails. But whether it is going to be used as a basis for a drug or in tandem it also depends on the stage, size and grade of the tumour. It should certainly be tested also on humans,” say the lead researchers on the project, Dr Hani El-Nezami and Dr Gianni Panagiotou, key members of HKU Food eSRT and SRT of Genomics, respectively. They led the study from School of Biological Sciences, Faculty of Science, HKU.  

Other key researchers include Dr Nikki Lee from Department of Surgery, Li Ka Shing, Faculty of Medicine, Dr Jun Li and Dr Cecilia Ying Ju Sung, School of Biological Sciences, Faculty of Science, HKU, Prof Jussi Pihlajamäki, Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland.

For further information, please contact:

Professor Jussi Pihlajamäki, University of Eastern Finland, Institute of Public Health and Clinical Nutrition, tel. +358 50 3440187, jussi.pihlajamaki (at)

Dr Hani El-Nezami, Hong Kong University, School of Biological Sciences and University of Eastern Finland, Institute of Public Health and Clinical Nutrition, hani.el-nezamy (at), elnezami (at)

Research article:

Jun Li, Cecilia Ying Ju Sung, Nikki Lee, Yueqiong Ni, Jussi Pihlajamäki, Gianni Panagiotou & Hani El-Nezami. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. PNAS Online Early Edition February 16, 2016, doi: 10.1073/pnas.1518189113