As I look back

Brain Having been involved in microbiology for so long it’s sometimes difficult to see the progress we are making. When I started out as a microbiologist in the 1970s the impact of molecular biology on microbiology was overwhelming, even if it took us a few years to think about what we should do with our new tools beyond expressing foreign proteins in microbes. With the development of PCR in the 1980s the flood of new sequence data and new species increased, and the 1990s brought us into the genomics era with the start of the Human Genome Project. But around the millenium it all got a bit cloudy for me and I wasn’t sure where we were headed any longer.

Many people would argue that CRISPR has been the great leap forward of the last decade, but I’m not so sure. To me it’s just another tool, following on directly from cloning and PCR. When people involved the first human genome CRISPR trials tell you they are “a huge undertaking and not very scalable“, they may have a point. As the NHS crumbles in the UK, what hope will there ever be for rolling out such expensive technologies worldwide? Anyway, back ten years….

As we accummulated more and more metagenomes, I still wasn’t sure were we were going. Was this just stamp collecting? Of course I shouldn’t have worried, because blue skies research is never a waste. The true revalation of the past decade has been the link between gut bacteria and the brain – the real game changer (Gut Microbes and the Brain: Paradigm Shift in Neuroscience). Who could ever have seen that one coming? The news that Parkinson’s Disease may be triggered (in those with a genetic predisposition) by the balance and shifts of gut flora is the real future. Forget expensive genome engineering, the future worldwide looks like faecal transplants (in the short term) and diets, probiotics and pills of freeze dried bacteria in the medium term. This is already happening in clinics to treat C. difficile colitis and other bowel conditions, but extending these treatments to the brain is the early days of a revolution. Forget moonshot-scale expenditure, the future is all about the bugs in your gut. The future’s bright. The future’s brown.

 

Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell 167(6): 1469–1480.e12, 1 December 2016. doi: 10.1016/j.cell.2016.11.018
The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson’s disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.

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One Response to As I look back

  1. Ed Rybicki says:

    I echo your sentiments: microbiomes and their influence on their surroundings (be it gut, vaginas, or seawater) turn out to be The Big Discovery. CRISPR is another toolkit to make what we already know how to do, easier.

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