Microbiomes: is there nothing that they can't do?

Microbiomes: is there nothing that they can’t do?

The volume of recent developments in preclinical and Phase II trials suggests there are still more discoveries to come from the world of microbes and microbiota.

Previously we looked at studies suggesting that neural disorders like Parkinson’s might not just be a brain condition but very likely have origins in the gastrointestinal tract.

Evidence in practise

It is generally accepted that intestinal decontamination with non-absorbable antibiotics such as rifaximin is an effective treatment for hepatic encephalopathy. Hepatic encephalopathy (HE) refers to changes in the brain that occur in patients with advanced, acute (sudden) or chronic (long-term) liver disease. It is one of the major complications of cirrhosis. It can occur suddenly in people with acute liver failure but is more often seen in those with chronic liver disease.

This suggests that gut dysbiosis and the ensuing metabolic consequences involving intestinal absorption of nitrogenous compounds plays a role in the progression of neurocognitive dysfunction.

Cancer is also a target

One study has suggested differences in microbiome in men with cancer compared with benign prostate hypertrophy. It found a higher abundance of Bacteroides massiliensis in prostate cancer and higher Faecalibacterium prausnitzii and Eubacterium rectalie in controls and suggested an influence on micronutrients [Ref 1]. Another study identified a 10-microbiome metabolic pathway score that may provide an additional risk factor for prostate cancer, and which is potentially modifiable [Ref 2]. Vedanta has developed a bacterial consortia, VE 800, which when combined with checkpoint inhibitors has been found to induce anticancer CD8+ T cells in animal models of melanoma and colon cancer, improving survival and showing infiltration into tumors.

The good, the bad, and the… dysbiotic

Clearly this emerging field has key questions to answer. The identity of “good” microbes in your gut or on your skin, for instance, is not clear, nor are the relative numbers that typify a “normal healthy” individual. Also, what constitutes an unhealthy or “dysbiotic” state: is it characterised by an increase in abundance of “bad” microbes, a decreased abundance of “good” ones, an overall loss of community diversity, or a combination of all three?

A growing market

Whatever the answers, microbiome treatments represent a potentially large market. One recent study by Transparency Market Research suggests that the worldwide human microbiome market will be worth $2.2 billion in 2020, reaching $3.2 billion by 2024. Diagnostics and therapeutics are the two main components in this market, with both predicted to hit an annual growth rate of around 9% by 2024.

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Research output is progressing quickly thanks to genome sequencing technology which provides fast analysis on the complexities of microbiome genomes. At the same time, however, there are new regulatory hurdles to face, with the FDA and EMA having to decide how best to monitor and control treatments such as FMT and live cell mixtures, as well as refining protocols to standardise testing between treatments [Ref 3].

Over this four-part series, we’ve discussed the fast expanding interest in altering the human microbiome to treat C. Diff and superbug infections, inflammatory diseases, cancer and cirrhosis. Successful preclinical and phase II trials that aim to rebalance the microbiome using genetically modified and non-modified bacteria, phages, probiotics, peptides and small molecule inhibitors will not only provide hope in the form of novel cures, it will also allow for the creation of a large pharmaceutical market possessing a great reach across multiple disease types.

References

1. “The role of gut microbiome in the pathogenesis of prostate cancer: a prospective, pilot study.” Golombos, D.M., Ayangbesan, A., O’Malley, P. et al. Urology. 2018; 111: 122–128.

2. “Metabolic Biosynthesis Pathways Identified from Fecal Microbiome Associated with Prostate Cancer” Michael A. Liss European Urology July 11 2018 DOI: https://doi.org/10.1016/j.eururo.2018.06.033.

3. "Faecal microbiota transplantation: a regulatory hurdle?" Frederick Verbeke et al. BMC Gastroenterol. 2017; 17: 128. Nov 28. doi:  10.1186/s12876-017-0687-5.