The Microbiome and Probiotics Will Change the World- Paul Wischmeyer M.D.

hello yyam it's great to be speaking with you today this is Paul wishme and I'm a professor of anesthesiology and surgery at Duke University and I'm thrilled to be here today to talk to you about how the microbiome and probotics will change the world and perhaps treat covid-19 these are my alignments um some would call them conflicts I hope they're alignments of Interest that's helped support my research and what we want to focus on today we spend a lot of time talking about antibiotics and how to eradicate bacteria but I'd like to impose upon you or or have you believe that bacteria are 100 trillion friends that we didn't know we had and that we want to keep around and that perhaps we should think about how we should give back B um bacteria to uh to our patients and perhaps to ourselves and there's a lot of information about giving bacteria and perhaps stool back to patients and to ourselves to care for ourselves things like FAL transplants there's books about how you can use your own stool to improve your health perhaps and perhaps we'll be prescribing stool and poop pills and and probiotics to our patients very soon with the data that we now have and perhaps even this will make a big difference in treating and preventing covid-19 so why should you care so much about your microbes well have you ever wondered why you get bitten by all the mosquitoes and your wife or husband don't when you go in the woods it's not because you're sweeter it's because the bacteria that live on your skin attract or repel mosquitoes and in in fact we're finding out that the bacteria that live inside our bodies inside our colons our intestines may even decide who we marry or have sex with in fact we know this is true if you're a fruit fly so we may find this out about humans as well and how do they all do that how do bacteria why are they so important to our bodies well what is it that makes us human is it our cells that make us human well we are 30 trillion human cells in the average body but 38 trillion microbial cells so cellularly we are more bacterial than human perhaps you think it's your genes that make you human well you have 20,000 human genes right now sitting in your home or wherever you are and 20 million microbial genes so we are 1% genetically human and 99% genetically bacterial so we're posed to answer questions about our bacterial cells and how we can use them to improve our health and so this brings back the question what's in our patient guts can it help or hurt them and what happens to it when we get sick well we know that many of the things that happen in the ICU derange and impair our microbiome or our bacteria they lead to what we call dysbiosis and these are things like sedativ opiates fos levels vas oppressors psychological stress and all the things that go with being in the ICU and so perhaps to restore this balance that criticalness and other things antibiotics cause we need to be giving back probiotics and resting the lawn that's blighted the normal bacteria that are killed with probiotics stool transplants or poop pills the kids at MIT will sell you their poop in a pill and tell you that it makes it smart that will make you smarter um the FDA has some questions about that but it's interesting nonetheless so if we're going to use probiotics and and microbiome related drugs how should we do it it needs to make scientific sense first and what is the science well we know that when a patient becomes sick that pathogens grow up all of us have pseudomonas living in our guts right now and when we become sick pathogens grow up quickly and they can talk to each other and they can recruit other pathogens and so we lose our normal bacterial floor and this leads to an invasion of bad bacteria much like when there's a hurricane in the US and all the people live in the city leave the city and looters come in and begin looting and they bring their looting friends and so this is a problem what we think is if we can give back normal bacteria through probiotics or stoal transplants what this does is it quickly outgrows the pathogenic bacteria and it protects the gut and tells those those looters that have come into the City and they're bad for to go away and just like lutters leave the city when the people come back it's true for bacteria as well and probotics have a lot of Direct effects on both viruses and bacteria there's many mechanisms by which they reduce infection and protect our bodies at at the fundamental level against infections and injury so what about things like covid-19 respiratory infections and pneumonia my laboratory has had a long interest in this and we've used lacopo and bifidobacteria to show that you can use probiotic treatments to prevent mortality from from pneumonias like from pomonis and you can see this data here we significantly prevented mortality and in fact when you give these probiotics to the animals after giving pomonis you can eliminate the bacteria and the Bal positive settings you can see this pneumonia animal who got ponus has a lot of bacteria in their blood the animals that got lactobac GG have none and we repeated this study many times and we also showed it was true imp peritonitis and it protects the lung you can see the pneumonia lung that didn't get probotics looks like an RDS lung or the probiotic LS do not and so what's the mechanism that begins to underly this and so we know that for instance t-reg cell responses reduce the injury that pneumonia causes in the airds that it causes and the death it causes well probiotics increase t-reg cells and help regulate the proper response to a major injury to the lung and so this is one of the pathways amongst many we think it works by this is a start basic science but not sufficient so how do we do this safely we have to make sure giving back bacteria safe well the US hrq health research quality Institute went looking for the harm from probiotics thinking they would find it they studied looked at 622 probiotic studies and what they found was there was no risk of Adverse Events even studies that go on for more than a year in healthy patients who get probotics you can see no relative risk of Adverse Events at all in fact in sicker patients there was less Adverse Events in people who got probiotics like critically patients versus non patients who patients who didn't get probiotics the propa trial is a trial you've probably heard of it was a uh pancreatic pancreatitis trial that gave probiotics and fiber to the small bow postpyloric and these patients got balis schia because those boluses didn't move and so what we learned from this study that that showed some risk of doing this was do not give probotics post pyloric in patients who have poor motility so again you want to always give them to the stomach but the conclusion of this hrq document was 622 trials shows there was not a risk of probiotics they were very safe and in fact maybe beneficial at the more sick you are so what happens to the microbiome and critically old patients what's this was a study the IU microbiome project that my group did with a number of other groups around the world and published recently with Rob Knight's group he's a real Maven in the probiotic field and we found extreme disbiosis this was our first publication 115 ICU patients four centers across North America mechanically ventilated more than 48 hours and everybody got antibiotics you can't be in ICU in North America for more than 4 hours notet antibiotics and you can see our results show that there was significant derangement with the ICU patients in blue and the normal healthy patients in red that were our controls there was significant derangement of the microbiome and massive change happened in just a few days and unfortunately the mouth the skin and the gut began to look Norm the same so we lose our barrier function we lose our diversity you can see normally there's a great deal of spread in the small dots between those three body areas they all come together as we get sicker and there's a massive increase in pathogens those red lines coming down of the pathogens and the normal bacteria the greens and the blues and there's massive loss at I Mission and discharge of the normal bacteria and the growing of the pathogens so does this not only affect physical outcomes or infectious outcomes but does it affect how our brain works delirium depression and other cognitive function well we know that the bacteria in our gut transmit or or generate neurotransmitters we call them psychobiotics and so there seems to be a significant effect on delirium potentially and depression from probiotics and so you can treat this as well so the cognitive symptoms may be relevant as well does it improve clinical outcomes well the clinical data says giv probiotics en large metaanalysis data this is a jam of paper looking at probiotic use for diarrhea 12,000 patients reduced antibiotic Associated diarrhea by 40% with good safety so again large large metalysis exist this was a prevention trial the NIH funded looking at laop GG to prevent Viller Associated pneumonia reduced villain Associated pneumonia by half 50% in patients who got laop GG and this was in the intention to treat group and ciff diarrhea went down as well this is a met analysis my group did against significant reductions in infections in many trials the sicker you were the more you benefited because we think the more your microbiome is deranged you can see there were a lot of studies that went into this and significant reductions in infection this is true in sepsis elective surgery trauma and many other areas where probotics have been shown to be safe and beneficial on Clinic iCal outcomes and this is the lmar trial you should know about especially when it comes to thinking about covid-19 this was published in nature five full pages of nature this was a 4500 well healthy infant study done in India looking at lacto faill plantarium plus a preotic versus a control and this showed a 30 to 50% reduction in respiratory tract infections and sepsis and death in those healthy subjects that got a probiotic versus those that didn't massive effect and again significant Improv movements in the primary outcome of sepsis and death 40% reduction significant reduction in lower interruptor respiratory tract infections including viral infections this seem to have a big effect on viral infections like covid-19 there's another large metaanalysis in Cochran showing that probotics reduce respir trct infections by almost 50% when they're used in large populations and again they reduce the length of that as well the length of the rest trct infection shortens it's a 10,000 patient meta analysis of symbiotics pro and prebiotics again reductions in R trct infections so we need clinical trials of this in covid-19 we at Duke are doing or starting a number of Trials you can see them all here one of the trials we're enrolling is prevention of covid-19 infection in family and caregivers of positive patients but we're also looking at hospitalized patients we're looking at nursing homes and a number of others we have an indd for this so this is a real drug study we're doing with lactobacillus GG and we've secured all the product we need this is the first trial probotics to reduce transmission we're trying to modify the microbiome we're doing microbiome measures every week we're having them send us their stool and a nasal swab for PCR for covid and we believe we can reduce symptoms and transmission significantly this is our website if you want to learn more about the study or if you want to participate please feel free to reach out you can see we're collecting stool and nasal swabs every week in the study and collecting the other things online so what have we learned so far as we close well first a healthy gut is a diverse gut and that the ICU and critical illness leads to a significant loss diversity of the gut microbiome which is associated with the poor outcome we need to correct this we need to be treating this this is a fundamental part of who we are we really live in a bacterial world and we can change this world and we think we can have a big effect even in covid-19 and reducing infections and helping people around the world safely and cheaply do that so perhaps there is something to prescribing poop or prescribing probotics or poop pills to our patients and we can resod the lawn that's deranged by antibiotics and restore balance and now with the modern microbiome analysis Technologies we can make it so easy that a child can do it and so I want to thank the groups that have helped me do this research the night lab um who helped me do the IU microbiome project and many other things and Tony Sun who's working with me on the uh covid-19 research Trials of probotics and the microbiome with that I'll be happy to answer your questions feel free to reach out on Instagram Twitter or email if you'd like some of these papers or have anything you'd like to ask and I look forward to hopefully probotics helping us fight this pandemic and improve our ICU patients carees outcomes thank you