Media

HKU develops novel probiotic mixture “Prohep” that may offer potential therapeutic effects on liver cancer

27 Apr 2016

Research team members: (from left) Dr Hani El-Nezami, Dr Gianni Panagiotou and  Dr Li Jun

A research team led by Dr Hani El-Nezami and Dr Gianni Panagiotou, of the School of biological Sciences at the University of Hong Kong, in collaboration with the HKU Li Ka Shing Faculty of Medicine and the School of Medicine, University of Eastern Finland, develops a novel probiotic mixture “Prohep” that may have potential therapeutic effects on Hepatocellular carcinoma.

Hepatocellular carcinoma is the second most deadly cancer type globally and accounts for most liver cancers. The research team found that Prohep, when tested on mice, could slow down the tumor growth significantly and reduce the tumor size and weight. A reduction of the tumor weight and size by 40% was revealed following feeding a mouse model with Prohep one week before the tumor injection (group 3 in photo). The findings have been published in March in the Proceedings of the National Academy of Sciences of the United States of America (please click here for the PNAS article),  a top international journal which publishes articles with original scientific research of exceptional importance.

1. Control group: fed with normal diet after tumour injection
2. Cisplatin group: fed with chemotherapy drug Cisplatin after tumour injection
3. ProPre group: fed with Prohep one week before the tumor injection. Other treatments the same as ProTreat group.
4.ProTreat group: fed with normal diet and Prohep after tumour injection

The animals were killed 38 days after tumor injection to quantify the tumor size.

Probiotics are live bacteria and yeasts that are believed to provide health benefits (for humans and animals) when consumed. The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extra-intestinal tumors remain unexplored. The research team has been the first globally to have applied probiotics in liver cancer studies and generate results.  

According to the findings, the probiotics’ beneficial effect is closely related with the abundance of certain beneficial bacteria that produce anti-inflammatory metabolites, which subsequently regulate the pro-inflammatory immune cell population via the crosstalk between gut and tumor. Modulated gut microbiota, when applied to liver, suppresses hepatocellular carcinoma growth in mice.

Prohep, the probiotic mixture developed by the team, its individual components have been studied in isolation demonstrating their ability to induce different biological processes altering the communication between the bacteria but also between the bacteria and the host, that influences host metabolism and disease risk or development. It has the potential to offer solutions for the future treatment, or development of alternative or complementary therapeutic and prophylactic methods for Hepatocellular carcinoma. (Note)

In light of the findings, Dr Hani El-Nezami said: “The successful demonstration of probiotic efficacy in retarding hepatocellular carcinoma tumor growth in pre-clinical model will warrant further testing of our approach in a microbiome-based intervention trial in cancer patients. The combined data from these studies could be applied to product development of immunotherapeutic drugs containing the studied bacterial communities. This will offer an opportunity for local pharmaceutical industries to adventure into this area of research to develop novel drugs, based on microbial ecosystems, to reduce HCC risks. “

He said future research would be to find out how to consume the probiotic mixture to obtain the best results, and to develop more efficient  bacterial cocktails.

Dr El-Nezami added: “Over the last few years a lot of studies that associate different disease types, such as infection diseases, cancer and metabolic diseases, with disturbances in the gut microbiota. However, in most of these cases the statistical analysis will propose just a couple of bacteria as the main contributors on the disease progression. For complex diseases, bacterial communities - 20, 30, 50 different species - are necessary for inducing the biological processes that will positively influence the host. Therefore the research team’s follow up studies on HCC progression and the interplay with the gut microbiota are in that direction, to develop more efficient bacterial cocktails. Moreover, there are many more parameters that need to be elucidated in relation to this study. Whether these bacterial cocktails are going to be used as basis for a drug or in tandem it also depends on the stage, size and grade of the tumour. It should ultimately be tested also on humans; this is the only way to get definitive answers.”

The commercialization of Prohep is being assisted by the HKU Technology Transfer Office and Versitech Limited.

Note: The potential of probiotics in offering cheaper treatment solutions for HCC 
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, the average cost is around US$6 000 per month for  targeted therapy Published cost analysis of HCC in the United States indicated that the mean 5-year net cost 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.

About the research team
Dr Hani El-Nezami and Dr Gianni Panagiotou, key members of HKU Food eSRT (Strategic Research Theme) and SRT of Genomics, respectively, 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.  

About Technology Transfer Office at HKU
The Technology Transfer Office (TTO) manages the use of the intellectual property assets of HKU by providing patenting, licensing, and other commercialization support to our researchers. Acting as the bridge linking HKU to society in the area of technology commercialization, TTO facilitates industries and businesses to access HKU’s powerhouse of knowledge, innovation, and expertise through close collaboration.  For HKU’s patents and technologies, please visit: http://www.tto.hku.hk.  Potential industrial/ business partners who are interested to discuss commercialization opportunities are welcome to contact TTO by email at info@tto.hku.hk or telephone at (852) 2299 0111.

About Versitech Limited
Versitech Limited, the commercial arm of the University operating on a non-profit making basis to promote technology innovations by HKU researchers. Website：http://www.versitech.hku.hk/.

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. Our biochemical analysis 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 tumor. It should certainly be tested also on humans.

For media enquiries about the research findings, please contact:
Dr Hani El-Nezami: elnezami@hku.hk
Dr Gianni Panagiotou: gipa@hku.hk
Dr Li Jun: h0992085@connect.hku.hk
or
Ms Melanie Wan, Senior Manager (Media), Tel: 2859 2600/Email: melwkwan@hku.hk, Communications & Public Affairs Office, HKU.