Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disease that has no effective treatment. Our proprietary probiotic mixture, Prohep, has been proven in a previous study to be helpful in reducing hepatocellular carcinoma (HCC) in vivo. However, its prospective benefits on the treatment of other liver diseases such as MASLD, which is one of the major risk factors in the development of HCC, are unclear. To investigate the potential of Prohep in modulating the development and progression of MASLD, we first explored the effect of Prohep supplementation via voluntary intake in a high-fat diet (HFD)-induced MASLD/metabolic dysfunction-associated steatohepatitis (MASH) murine model. Our results indicated that Prohep alleviated HFD-induced liver steatosis and reduced excessive hepatic lipid accumulation and improved the plasma lipid profile when compared with HFD-fed control mice through suppressing hepatic de novo lipogenesis and cholesterol biosynthesis gene expressions. In addition, Prohep was able to modulate the gut microbiome, modify the bile acid (BA) profile, and elevate fecal short-chain fatty acid (SCFA) levels. Next, in a prolonged HFD-feeding MASLD/MASH model, we observed the effectiveness of Prohep in preventing the transition from MASLD to MASH via amelioration in hepatic steatosis, inflammation, and fibrosis. Taken together, Prohep could ameliorate HFD-induced MASLD and control the MASLD-to-MASH progression in mice. Our findings provide distinctive insights into the development of novel microbial therapy for the management of MASLD and MASH.

Cancers are causing millions of deaths and leaving a huge clinical and economic burden. High costs of cancer drugs are limiting their access to the growing number of cancer cases. The development of more affordable alternative therapy could reach more patients. As gut microbiota plays a significant role in the development and treatment of cancer, microbiome-targeted therapy has gained more attention in recent years. Dietary and natural compounds can modulate gut microbiota composition while providing broader and more accessible access to medicine. Tea compounds have been shown to have anti-cancer properties as well as modulate the gut microbiota and their related metabolites. However, there is no comprehensive review that focuses on the gut modulatory effects of tea compounds and their impact on reshaping the metabolic profiles, particularly in cancer models. In this review, the effects of different tea compounds on gut microbiota in cancer settings are discussed. Furthermore, the relationship between these modulated bacteria and their related metabolites, along with the mechanisms of how these changes led to cancer intervention are summarized.

The probiotic mixture Prohep has been studied as a potential therapy for liver diseases such as MASLD, MASH, and HCC. To evaluate its safety, we conducted an experiment on CD-1 mice to assess its acute, subacute, and subchronic oral toxicity. The results showed that Prohep intake did not cause any morbidity or mortality, nor did it produce adverse changes in body weight, histopathological, haematological, or biochemical parameters. Therefore, Prohep is considered safe for consumption, with LD ₅₀ of Prohep being higher than 5000 mg/kg (category 5, LD ₅₀ > 2000 mg/kg) and no-observed-adverse-effect-level (NOAEL) of Prohep being 2800 mg/kg. Furthermore, we investigated the ability of Prohep to modulate gut microbiota under both normal chow and high-fat diets. Based on faecal DNA sequencing results, a continuous 28-day course of Prohep supplementation is required to achieve complete reshaping of the gut microbiota composition. This 28-day supplementation window may therefore be informative for designing human dosing regimens aimed at inducing durable, clinically meaningful modulation of the gut microbiota. The modulatory effects of Prohep supplementation on gut microbiota were still observed 28 days after withdrawal. These findings provide valuable information for the pharmaceutical use of Prohep, including its safety and optimal duration of probiotic supplementation.