From bench to bedside - the continuing journey of Akkermansia muciniphila
Patrice Cani is a Research Director whose main interests are the investigation of interactions between the gut microbiota, the host and the specific biological systems in the context of obesity, type two diabetes and cancer. He described the “long journey” his work on this bacteria and said it must continue.
He opened his presentation by explaining that the composition of the gut microbiota is different in multiple conditions including cardiovascular and liver disease, appetite disorders, arthritis and eczema.
He said: “If you analyse the microbiota from someone who is suffering from a given disease, you will find a difference and this is clearly, most of the time correlation and not real causation. This is something we have been working on in the lab over the last 20 years.”
During his talk he told a room filled with cohorts that he wanted to hone-in on one specific bacteria - Akkermansia muciniphila.
Abundance in gut
He said: “I want to discuss with you today one specific bacterium that has been part of my work for more than 15 years and that is the history of Akkermansia from the bench to the bedside – we know that there is quite an abundance of it in the gut.”
Patrice explained that numerous correlations had been observed and that a lot of evidence had shown a causal beneficial impact of Akkermensia in a variety of preclinical models. He said taking these revelations to humans is the next logical step and that many obstacles have been overcome.
“In 2007/2008 in the lab, we started to analyse the microbiota from different models - titled use obesity, genetic obesity and diabetes. And for all the different experiments we did we found that there was a decrease in the abundance of Akkermansia,” he says.
Interestingly, on the opposite side, Patrice said that his research had shown that lean mice had a high abundance of Akkermansia and that this was a simple correlation.
“If you think about humans now, there are many, many papers clearly demonstrating that in those suffering from intestinal inflammatory bowel disease, obesity, type two diabetes but also elderly subjects or people not responding to checkpoint inhibitors to treat certain cancers or neurogenerative diseases – they all have a lower abundance of Akkermansia."
Patrice said he and his colleagues as well as others found that analysing the microbiome after surgery such as gastric bypass – losing weight quickly with a quick resolution of diabetes that this is linked to a change in microbial composition including Akkermansia.
While testing has been carried out on mice since 2010 and remains ongoing, human testing only began in 2015 and finished in 2018. Although getting to this stage was not easy as it was a challenge to access but Patrice said through the grit and determination enough data was collected, “this was interesting,” he noted, “but we all wanted to see what happens in humans.”
While it proved difficult to test on humans, this was eventually achieved by Patrice and his team and they now have a medium that is suitable for human use. During a study they administered placebo, live and pasteurised Akkermansia to those taking part. They discovered that pasteurising Akkermansia improved the phenotype by stabilising it. The humans in the study had no change in their diet and were not taking medication. They were however obese and/or insulin resistant.
“So the results were very interesting for us, they showed resistance to insulin reduced by about 30% and there was an increase in cholesterol by about 8.5% which is not huge, it is not a statin but it shows what you can find by using specific dietary interventions and it is very important to accumulate the different factors. We were surprised to see a link to hepatic inflammation markers in liver enzymes GGT and EST and believe the Akkermansia reinforces good biofunction lowering hepatic inflammation. Cardiometabolic risk factors were lowered by pasteurised Akkermansia.”
Patrice said that it is essential to continue with this work because the results have been so promising.
“We have found the bacteria, isolated it, tested it on mice, moved to humans and now on to the markets and this is what will happen here because Akkermansia finally got approval from EFSA as a novel food and I want to thank all the different collaborators sincerely – this has been a very long journey.”