Inflammation: Is the Gut the Driving Force of Systemic Inflammation?

as Sarah mentioned I'm a surgeon I do general and trauma surgery and I work in the ICU but my PhD workers in nutrition and so it's been an interesting run of 35 years now bringing nutrition sort of back to a surgical practice the concept of where I really work is a concept of getting people tuned up prior to a savage act to me or penguins ectomy or big operations and it's also allowed me to work on several things I do a lot of international work we work in chiang rai Thailand and then Laos and Finch in Laos on several big projects with rice and several things so I've had a very been very lucky my career to be able to work on this concept of good nutrition changing things changing outcome changing cognitive function and both and then come back to a clinical setting and work at the Medical College or at the Oregon Health Sciences where I work in Portland so you know if we look at our global health challenges they're really tremendous I mean really but it revolves a lot about this concept of inflammatory disease you know we're looking here and really if we look at the diseases other than the communicable diseases which we see overseas we're looking at cardiovascular disease cancer chronic respiratory disease etc and those are big burdens I mean they're huge you know I think this quote by Napoleon very well he says the winner of the war will be able to control the women of the battle be able to control chaos we're really our approach currently is chaos we've got government that doesn't really regulate much especially in the last few years you know they take away a lot of the things we get to get put in our foods there's a lot of craziness I mean you know for years we've been having policy that hasn't really fit with the nutritional aspects I mean we get billions of dollars to healthcare but we don't really address what's the bottom line to the disease we're not addressing the inflammatory process with our education we know oh it works if please start teaching kids and the five and six and seven-year-old that'll they'll take on that message and that's worked and we've seen that work and that's a lot of what I'm doing now at the end of my career is trying to get these programs into schools so we can teach these kids and start from day one with rock with progress but again you know we look at inflammatory States to obesity cancer inflammatory bowel disease etc all starts and if we look at the this slide is very interesting it talks just about it shows nicely what's happened here with all the infectious diseases have germ end ously dropped okay this is clearly not just fifty years ago but this is starting about 1950 to 2000 of TB hepatitis rheumatic fever measles mumps all coming down because immunizations and a public policy which affects those but look at our inflammatory diseases growing up almost paralleling in fact about ten years preceding what we recognizes our obesity crisis so I think inflammation then is a root to many of these things and as you know this is not new John Hunter famous biologist anatomist from London in 1794 showed us that inflammation has many diseases associated with many diseases so I mean it's a couple hundred years old we've realized a connection so I think that's the issue so if we look at diseases associated with inflammation it's tremendous so you know you can see this big issue is virtually everything we deal with on a day to day basis in a clinical setting is inflammatory disease I mean you know even as a surgeon we don't deal with infectious disease anymore except for necrotizing fasciitis which rarely comes to and comes in once or twice a week that's about it but so what's the driving force I mean what is it what can we treat I think we have to think about the GI tract as the main source okay so if we think about I like to think of the GI tract I certainly like just a tube going through us you know kind of like a river going down through us right but not all that like the skin that has to protect us from the outside environment you know from the toxins we see and the things we put on our skin but it also has to selectively absorb nutrients so it has the bigger problem it has to absorb some things without taking Ana toxin so it has to keep out the bad stuff and taking the good stuff and so there's enough endotoxin than just one person in this room to kill all of us so that's how efficient our gut is I mean that one cell layer thick you know that we see down there on the brush border and the area out here is basically keeping us from dying because the endotoxin in our GI tracts and that's produced by the bacteria and produced by the you know purify e.coli into toxins etc that we see every day we use clinically to induce hyper dynamic State so I think think about what the GI tract so we're walking a thin line you know we're walking that tightrope basically between barrier functions symbiosis homeostasis which is we'd like to permeability and dysbiosis information so I think that's why very little change you know in our microbiome and the bacteria can make that difference so what I like to think of the gut as orchestrating the inflammatory response you know because when you start reading and you know drilling down this it really is I mean if we think about that we've got g-protein receptors here that were responding to metabolites and bacteria we've got dendritic cells here that go out and sample the environment of what's going on and tell the immune system what to do basically comes back and regulates the t-cell the t seller regulates the b-cells we know that these these basically the muscularis layer is altered by what's happening in the bow we see this every day in the clinical setting with once we've disrupted their bowel and done surgery we know we all to the mechanical ability to Paul to parasol's so really we have to think of the gut as changing we also now know the association between the brain and the central nervous system I mean the gut brain access is a huge push now and where did this all start well it's actually fairly new 1977 was this paper by Ben Iseman University Colorado a surgeon who said maybe the gut is the source of multiple organ failure before that before 1970 we all said it's just beginning of my surgical training we all said it's related basically to infection and all these people died and those they were dying of infection then then started with the concept of maybe it's multiple organ failure related to this uncontrolled inflammatory response not necessarily infection although we spent the next twenty years going through papers that would say there's inflammation inflammation but we never could isolate the bacteria remember the in your colon you've got several thousand back different species there's at least 1,500 different species in the US of which only about 800 or so or culturable so we're not able to culture them until we gather more modern techniques we didn't really know so and all these people with these thing germ free animals don't respond the same so maybe there's something going on with the bacteria living in our gut and so then we start saying well what about the microbiome and this this group as you can see is almost identical to the previous one inflammation diseases related microbiome changes disease is related and they're almost identical we get parallel so let's look back at the sort of this history of this concept of microbiome okay so mention a cough really is sort of the father of our current concept of microbiome mission accom the Nobel Prize in 1904 for discovery of the macrophage okay and then he took his money that he won the Nobel Prize with he decided his interest was to why do certain populations in the world live longer in small villages segments and different cultures live longer than the surrounding villages so Bulgaria is where he originally worked so he went the Yucatan Peninsula and found a segment that lived 20 years longer than the rest of the area people in the area he went to north is now in North Korea dependent Corian peninsula found a segment of people that live longer and he studied five different segments around the world they were an interesting paper in 1907 he said that there's the only thing they have in common was all of these cultures that live old groups that live a little longer than everybody else in their culture all took Daly fermented foods so in North Korea it was kimchi in Yucatan Peninsula was fermented llama milk okay and Bulgaria was cow's milk so they had a lactobacillus species intake on a daily basis so that really got this whole concept started in fact he named lactobacillus bulgaricus which was the first lactobacillus species named as you know in the United States of America be called a yogurt you've got to have lactobacillus bulgaricus by definition so that's followed us along so we know then also the surface of the GI tract is about the size of a tennis court so literally if we take out our intestine we lay it out we take all the micro villi spread them out there about the surface area of this room and you can imagine that exposure what it takes a little bit of toxin in an area like that and we know there's a million bacterial genes and about 20,000 human genes and our different parts of our body have a different microbiome specific the weather there's the skin or the oral pharynx or whatever you know and we have about a thousand species we can get by culture guy University of California Davis spent his life culturing human stool and in about 1985 he published a paper saying there's 750 species in the human stool took about two months to culture them all out all the subspecies I thought that was interesting the poor guy he did his own stool I thought it was really strange when he put his kid's stool and I have those poor kids I feel all dad not those rectal swabs again you know so so you know so when you start seeing that you said well then we started seeing changes and our ability based on some oceanography guys we're able to cope non-culture by using 16s ribosomal units we can now say we know we've got about 12 to 1,500 species that could be argued maybe more maybe less we know the humans living in the United States have about 1213 our species in our colon if we go deep into the Amazon to a group that's never seen Western civilization never had food that's you know done what's done to our food in our society they have about 4000 species so the variety has decreased that's one big issue variety is protective because there's redundancy so the number of bacteria live in your colon helps us survive these perturbations which we see normally through our routine daily life well if you live in the deep in the jungle and you don't eat things in the Western society we don't need emulsifiers and pesticides and sweeteners and all these other things we do we see the variety in your bacteria living in your colon or higher now I'm not saying they live as long as we do in fact they live shorter than we do so I'm not saying we're all it's all bad so if we think about this concept of microbiome I came to us from Joshua Lederberg another Nobel Prize winner and he learned it he warned his Nobel Prize by describing how bacteria transfer genes and things like that but he said when they start talking about the human genetic machinery the human genetic potential we have to look at the whole story that the bacteria as you've seen in this conference the bacteria living in your GI tract have epigenetic changes they will change on a day to day basis that can change your genome expression can change your phenotypic expression not the genome but change your phenotypic expression of your genome through epigenetic changes so we have to get include the bacteria the fungi the viruses in the archaea which are sort of a calf whey protein halfway prokaryote halfway eukaryote so if you look at that what are we done into Western society change our lifestyle sedentary lifestyle newborns the third of kids in this clip actually about 24% done in this country now are born by c-section okay Muniz ations domestic pets parasitic infected refrigeration and that we get down here where we start and see changes and as you've seen in the earlier lectures the way we process our food additive emulsifiers sweeteners i antioxidants preservatives and sect asides great data coming out now on roundup very interesting data how it alters your microbiome and it's in everything okay and then we increase use of antibiotics whether indicated or not we have good studies showing about 50% of the antibiotics are not indicated there's no bacterial cultures found but given because that's what the patient's want this is a good example here this slide shows us what happens to bifida bacteria Bacteroides one of these substances Bacteroides with the single dose abroad of clindamycin which obviously good to kill an ant I wrote back to razors anaerobe look at this they took here they zero the long-term effects of seven-day course of clindamycin on Bacteroides it takes almost a year to get that back to early species back up to normal a single dose of broad-spectrum antibiotics wipes out your normal flora I know that when I give my patients pre-op antibiotics I know I'm altering their floor the worst is cipro we don't give it as a prophylactic antibiotics grant program the highest cause cipro is the highest inducer of c-diff clustering difficile clustering does he'll called cause 24,000 deaths in the united states in 2013 death 24,000 deaths I take out a colon about probably four years ago once a month proceed if sepsis someone dying of c-diff sepsis right took out their whole : now it's about we're down because our hospitals way tennessee did because of our probe bag protocol i'll show you data for though i don't know so the microbiome there's all kinds of good data again I don't board the details but things like the average you know by age 10 the average Americans taking ten courses of antibiotics 50% of pregnant females receive antibiotics during pregnancy these have dramatic effects on our microbiome which we have to think about these things are we doing the right thing you know so if we think about the microbiome I like to think of the microbiome in fact as an organ just like your kidney or your brain or your heart your liver because what does it do for us and that it's not just passive there like we used to talk about the microbiome now is actively involved in day to day metabolism it metabolizes drugs there's your very good data now that if you're taking 5-fu for chemotherapy for colon cancer if you have a sterile animal that takes five of you it takes three times as much five after you to get the same killing effect we know that the bacteria to metabolize 5-fu to becomes more active in killing cancer so the mat the microbiome helps is a metabolize a drug that produces a myriad of vitamins and short chain fatty-acids we know now that seven to 10% of your leucine losing the major anabolic amino acid that's the on signal for protein synthetic machineries in the cell we've got that's hard data we know seven to ten percent of your leucine comes from colonic production by the bacteria we have a transporter in your colon now that will transfer inducible to translate amino acids we say medical students are still taught today that the only reason for the colon to absorb sodium and water there's no nutrients absorbed but that is absolutely wrong short chain fatty acids now amino acids are absorbed from the colon small amounts that would be no acids hormone regulations immune function maintain mucosal barrier those stains are lost when they lose our normal microbiome so I think we got to think of it that way we know that the medical community your guys are gonna be much more accepting of this than the M is used myself and fighting a losing battle for years but I'm starting to win the battle and you know in 2012 we started hearing about the microbiome inlay press the cover of The Economist magazine microbes maketh man okay Scientific American you know sort of a lay scientific journal we started seeing 2012 so starting to see a few things come in and now virtually every major medical journal in scientific journal it's got a major article on microbiome at least once a month it's everywhere nature man is a surgery JAMA all of them in 2018 routinely because it's now part of our normal routine it's hard member it takes us 10 years to go from science benchtop science the clinical use and we're just now coming back because we've had the science for 20 years the survey just done a month ago and just published a month ago done about a year ago in Canada against pharmacists across Canada the interviewed like six hundred pharmacists would you ever prescribe antibiotics for an ICU patient 82% of them said no we don't think it's safe just writes hundreds of articles prospective randomized double-blind trials in two and three thousand people showing that it is safe in an ICU setting so needless to say this is what we're dealing with we I have infectious disease doctors of my hospital still think we should not be given bacteria we should be killing bacteria okay I mean that's what they told me when I first got I moved from Georgia to Oregon fifteen years ago I took a pocket full of protocols with me cuz we had a nice you protocol in Georgia which took me a year to you go and took me three years they're going in Oregon you think in Oregon I'd be a little more progressive you know but they weren't they said Bob you can't be given the sickest people in the hospital bacteria I go but here's the data we don't care about the data basically okay so so here's all these species we talk about you know but when he's talking about species now knowing the next talk will talk about the importance of strain but remember we have species and then we have strains and just because you have a species it has one effect doesn't mean all the strains are gonna have that effect so we know that everything affects the microbiome it takes literally very little to affect on microbiome on a day to day basis I'd like to look at this just international travel we've got three studies now the show and you get on a plane in Los Angeles San Francisco and you land in Thailand your microbiome was dramatically changed a 16-hour flight change remember the half-light these things aren't over in five minutes to 30 minutes they divide 16 an hour flight you get a lot of subdivisions you got a lot of epigenetic changes that can alter them my favorite study is different hearing dogs when you when they took a family before they bought their dog they cultured everybody in the family the oral pharynx the stool the skin everything different places on the skin the hands and then they did a five-day tour three days later seven days later 14 days at a month later and guess what all the humans living in a house became more like the dog and the dog became much more like the people and guess who's the fastest to change kids because I know like with my dog but my grandkids come to the house he's in heaven because they drop all kinds of food and if they didn't drop it they leave it on their face and he gets it off their face so I think it really happens so so anyway all these things contribute to the microbiome and the rapid change is altered intestinal permeability once we get dysbiosis remember variety is your friend we want a variety of these things we don't want to see decreasing Friday and one broad spectrum our bikes like cipro takes it from thousand species to about 250 within 12 hours so that's dramatic we do I'll show you some data in the ICU but this think what if you think that happens in the community setting what happens in the clinical setting what happens when someone gets admitted and I'm a nice you doctor you know i surgical ICU look what happens Raaj victim attaboy Aurel antiseptics proton pump inhibitors vasopressors opioids decreasing normal nutrient delivery parenteral nutrition starting someone on IV feeding NPO IV feeding they go to about a 150 species within about 48 hours from a thousand to a hundred and fifty when there's nothing going in the gut within about 24 that's to work out of Michigan very good work out of Michigan and that's a pediatric population okay invasive devices good study here people I said well just living and like just working in the hospital make sure at higher risk because you have the exposure of these bacteria look at this this is a very nice paper originally published with culture data in 1969 the New England Journal of Medicine but now it's been repeated with our 16s molecular mechanisms so these are people living in there been not in the hospital for six months they've not even walked through a hospital normal healthy free living people this is the oral pharynx microbiota this is just a their swab they swab to do deep back of the mouth okay look at the number of pathogenic gram negatives for nothing hospital workers no difference if you're mildly ill not requiring hospitalization no change but look at this moderate though look what happens they're critically ill people rapidly changing because the critical illness so that's what we have to define we have to maintain a healthy microbiome sort of it with these commensals and symbionts and not get into the situation where the path or biome remember we don't necessary premium bad bacteria we allow with normal things the bacteria living there change they change their phenotype because the opportunity things now here's a good example here is Pseudomonas which you knows an aggressive Pseudomonas can be aggressive this is the same sorta mones here and you'll notice on the left here when they've been exposed to opioids they become aggressive okay now we have endogenous opioids okay you can do this with external opioids or endogenous opioids so the back you're saying hey something's going on here to have this much opioids I'm gonna become aggressive I'm gonna now attached to the bukoza so that bacteria which is normally living in your colon we all have suited Morrison our colon living there happily doing fine saying things are fine I got plenty of food coming downstream 37 degrees pH isn't because it's normal there's no sense of stress here and then you give it an injection you give put in the media opioids or a dodges opioids or lindo toxin has been repeated many different things and you start to see those bacteria clumping and expressing on their cell surface an attachment molecule to allow them to become invasive that's becoming that's the problem okay that was in science magazine John Reverdy has taken this concept and really brought it to us from Chicago from University University Illinois so what he said is that we have a microbiome which becomes a path or biome when we're stressed multiple operations whether it be mental stress or be work stress stress changes in microbiome okay so I don't want to bore you a bunch of rat data but this study is very illustrative what this shows us here is two animals one gets a sham operation ed to get to hepatectomy so the half delivers removed okay that's pretty big stress on humans or on rats okay but in before they did that operation they inoculated in their cecum this bacteria ok this Pseudomonas okay so they inoculate both groups with it with the cecum and then they operate on so one gets a sham operation open and close no real stress animal wakes up runs around the cage hepatectomy they come out they actually do pretty well they come they start wearing around the cave but they're little so is a significant stress okay then one 24 hours later they kill the animal take out the bacteria isolate the Pseudomonas now and then look at it okay and look at the survival the animals okay 100 percent survival and the animals that got a sham operation remember it's the same bacteria just a different operation the animals that got hepatectomy 100 percent mortality so just having an operation cause that Pseudomonas to become from benign to aggressive it and lethal that's why it's important to maintain a healthy microbiome during illness this shows you if you've had identify acts in the prior six months prior to an ICU stay look at the mortality if you're sick in the ICU at 30% of increase in mortality if you've got any antibiotics and the prior six months prior to hospitalization so what can we do there's lots of mechanism how does have you know how does having the right bacteria help us having a probiotic situation help us competitive inhibitions it inhibits this is like a basura inhibiting staph aureus it causes an introduction of heat shock protein which is the protein produced by your cells to prevent stress from a prevent injury from a subsequent stress tight Junction proteins no we'll talk about this it maintains the glue that holds your intestinal cells together not to allow the toxins in that's the bottom line the nose it enhances mucosal blood flow we know that having the right bacteria increases blood flow 30 to 50 percent this is a germ-free animal this is a animal that got bifida bacteria maceda 50 percent in Korean blood though within 24 hours the heal mucosal lesions you've got to have good blood flow increases GI motility stimulates gut immunity helped maintain the normal microbiome at sea deaf colon right there and then butyrate butyrate we used to think is only in the colon and it made by the bacteria fermentation of good fibers of soluble fibers is our main source of butyrate production it's about eight millimole and Nichola it's about 8 micro mole and a serum we now know there's a transporter a short chain fatty acid transporter in the colon to make the concentration going from low and it wasn't discovered till Ganapathy in 2005 discovered the short chain fatty acid transport in the colon so this relatively new stuff so now we know that because we used to say why is that people have less cancer when they have high fiber diets they have less infections when they have high fiber diets now we know that as you we produce short chain fatty acids they get absorbed and we see increased killing by the macrophage this is a macrophage right here it's a small picture there's a little gram-negative ecoli right there you know there's a green spot for that magnifies to kill that bacteria what has to happen first it has to recognizes e.coli there just to send out a pseudopod that's a pseudopod there this is a macrophage sending out a pseudopod it engulfs that ecoli and then produces an oxidative or nitrogen's birch was killed yeah didn't ecoli we know that when you got short chain fatty acids bound to that macrophage there's nine or ten different binding sites on a Mac Rivage when you've got why you've got butyrate bound to your macrophage your killing is tremendously improved you kill about it's some people asked to meet up to 20 bacteria before the cell undergoes apoptosis normally about nine bacteria are killed by a macrophage before undergoes a apoptosis when you enhance the killing ability of the macrophage you get better so this is just a list of the short chain fatty-acids stuff it's tremendous big list we I working on we're working on several projects with our cancer group we've been very lucky we've been well funded by our cancer group this histone deacetylase we know is the issue and sort of the promoter for colon cancer we know that's now decreed we can decrease that promotion when they have plenty of the right microbiome around so this is new data here very interesting we used to say what is it why do people do better with their rehabilitation after surgery when they've got short-chain for them they have a fiber diet which gives them hydrates of butyrate so this paper is very interesting short chain fatty-acids enhanced muscle function and mitochondrial biogenesis so when you've got butyrate on board circulating around and now you're rehabbing after big operation or after a stroke we know that essentially potentiates the effects of exercise the muscle maintenance by enhancing the number of mitochondria within the myocyte very interesting work so let's look at a couple of scenarios here that got about 20 minutes left so I got leaky gut okay diabetes and depression leaky got we've all heard about you know and I have to say on the I believe in leaky had for a long time the MD size my partners go give me a break you know a leaky gut you know business so you know but there's data supporting and there's a data refuting you know so that I give you an equal balance there but gut permeability and we know the definitions leaky gut refers it is but you know sustained mainly by nutritionists and practitioners of alternative medicine so basically saying md's don't believe it that's probably true okay MD answer when you have done Kirby who's chief of GI up at Cleveland Clinic or chief of these GA section MD Stan points very gray area so we don't really know we're not saying it's not there but we sort of don't you know sort of wonder you know so basically see all these sort of nebulous symptoms right bloating gas cramping fatigue you know multiple organ failure sepsis in an inpatient setting and then constipation behavioral change the anxiety you know those are all kind of great hard to get an objective prospective trial of these things so again there's lots of questions but remember our gun has got many different protection mechanisms we've got non mechanical mechanical the brush borders well healed they rapidly turnover number three to five days in the base of the crypt on top of the villas and they turn it over the mucous membrane is very thick so the tight junctions are pretty well maintained and pretty healthy but it doesn't take much to change that remember microbial diversity as we showed already changes rapidly is really what protects us so so diseases associated then with my leaky gut is so many again hard to put a finger on a lot of these things you know fibromyalgia depression I can tell you in the clinic when I see someone come into the diagnosis might with gi complaints I brought in my nutrition clinic as well as my surgical clinic I see a lot page from a chronic abdominal pain and I see fibromyalgia and I go oh god here we go you know because I you know it makes me nervous because I think what are we gonna have here you know fibromyalgia and a chronic abdominal plane I'm thinking oh it's gonna be a long day okay so okay so you know because there it's hard again to put a handle on it so there's all kinds of methods which we look at the mucosal maintenance and barrier we know that some of those are disrupted and some people just really a normal life we know chronic fatigue in fact has alterations by some of these mechanisms which are done in animal models it's easy but it's tougher in humans to prove it so again it's hard to say so what do we do how do we recommend treatment well maintaining visceral blood flow the right microbiome for the clinical setting early and real feeding and probably with early enteral feeding and we haven't one project going on now with organic food blunder eyes dove granting food versus the top-of-the-line formula for ICU patients and so if people are quite shocked when we start showing look at the microbiome variety here versus this you know that'll be published in about three months we got a tumors two more patients enroll so you know it's a broad and randomized prospective blinded trial we've even had to put foil around the line so if nobody can tell what's going through them so so we minimize pharmacological agents you know lower the inflammatory stimuli anti-inflammatory agents you know dietary changes organic foods decrease emulsifiers if you ever want to see what happens to microbiome were taking the salad dressing tell those emulsifiers just every virtually every cream salad dressing has that is I went home after I read those articles in nature and science I mean hard core science articles I went home and cleaned up my refrigerator through a way less of my wife because what the hell's going on here you've read you know I go don't eat that stuff anymore yeah so anyway I go any quills one what about obesity well we know this is here you can see the South really takes a hit this is BMI okay this is hypertension and one of these hypertension ones diabetes and that can't read that you think Adam either they can wait yeah physically inactive yeah the glasses are not good for distance so but you can see they all seem to have a pattern here the southeast North Carolina is in there you know so but remember that sort of obesity is counter-intuitive right so we have you know it's a life we always used to say what's a lifestyle choice people they have lack of you know willpower etc that's really not the case and I tell you for twenty years I did bear a surgery not because I wanted to because I work for the Medical College of Georgia and nobody else would do it so I had a lot of bariatric cases and I used to go you know they just have to quit even okay that's not the case I've learned that through my studies and obesity and multiple projects have been on NIH funded stuff it's a mullet snot just eating tuna it's not a single disorder there's several dozen genetic phenotypes end up being related okay but mainly it's inflammatory remember that obesity is inflammatory disease we know that people have higher CRPS we have all the inflammatory markers are up at obesity so that sets them up right if we look at look at this with diabetes a close association with diabetes type 2 diabetes is proportion of disease's prevalent attributable to obesity type 2 diabetes 57% of the type type 2 diabetes in this country is related to obesity so if we can cure that if we can get these people eating right will make a difference that's not just one references they're all 2015-2016 references ok cancer 30% of the cancer to be from changes and diet you know gallbladder disease hypertension etc look at the cost difference when someone comes into your emergency room with chest pain with obesity 41% higher cost again the government should say we're paying a bill for 60% of this healthcare if we just managed obesity or healthcare costs that go down tremendously so our education programs I don't mean to get a that little box but that's where we need to be focusing so we get this metabolic information right we see the pancreas altar we see muscle altered we see you know basically sarcopenia with increased fatty concentration of muscles or you the functional muscle is very poor it's a little great inflammatory process so the question then is can we by controlling diabetes obesity and diabetes change this trajectory that's really the question well look at this we know that obesity is a tremendous change here this is lean this is bacterial diversity which I talked about number is protective this is right here lean this is obese you can see as we get more obese we see changes and we see increased activities and less for mega T okay so this is again this is a very good study here on human uses transplanted stool so they came they took what they did here was they took humans that were obese and humans that were thin and they transplanted that stool into a germ-free Mouse and then said what if sorry humanized GI tract germ-free mouse and they showed that guess what the people that were obese to wrap the rats rapidly started gaining fat mass default microbiome from the thin people they stayed normal so obesity was transplantable by transplanting the microbiome from a heavy person to it from a thin person compared to a thin person we know that our Western diet alters microbial diversity in mice again germ-free mice we take Weston put him on a McDonald's diet and Burger King and Taco Bell and all these others and guess what happens we change it we decrease diversity we encase for making these we decrease Bacteroides remember that switch we see and even with the people that lose weight we see a switch back after gastric bypass we see a switch back to a more normal lean persons not that I'm saying gastric bypass is the answer you know increasing body fat so again we can change these with diet this is a very interesting human study ok what they did here was they took humans right and then they took some of their stool and they gave either their own stool back to them or they take stool from a lean person non-diabetic and give that to him there's a stool transplant program in humans and then they looked at insulin resistance so did insulin resistance change when a person with heavy person with diabetes gets stool from a light person ok a lean person and you can see there absolutely no change in the ones who've got his own stool back didn't change but there you can see the insulin resistance goes down tremendously when they get stool from a lean person so big difference germ-free my studies you can see this is again I'm going to board the details but the bottom line is if you give the bacteria to the wrong bacteria germ-free animals will rapidly go rapidly game you can see mice are protected germ-free mice if you give them this diet induced with no bacteria in your colon guess what you can't make them fat even with the McDonald's diet you give the same animal normal bacteria they'll get a gained weight germ-free mice don't gain weight so again the endotoxin you know another way to get blue great information low gradient oxidant causes the same changes in the bacteria as well as in the liver feeding high-fat diet increases permeability we're back to the idea that this fat changes the microbiome changes no it wasn't the fat that causes it was a microbiome changes that cause a loss or loss in these brush borders these glue that holds our cells together inducing a chronic inflammatory State so again it's just a diagram showing the same thing change in bacteria causes loss of this brush border causes changes in the tight junctions thereby we increased fatty liver we know that's the case now so again very metabolically active by changing in bacteria and what about the brain can we change cognition well we now know that in fact recently shown that we can give gut microbial access involved in behavior neurogenesis neural plasticity we can give the right probiotic and see those changes we can see significant changes in microbial cells we now have human data on microbiome there's a day now prozac versus probiotics and they have almost identical or decreasing depression okay so that digs aiya tea and stress depression you know a postive obsessive-compulsive disorder ADHD in others remember that 90% of the fibers in your vagus nerve where we talked about the tenth cranial nerve 90% of those fibers are going to the brain not coming from the brain so what does that tell us just remember that the two biggest nerve innervates - almost the transverse and left colon the whole right : so it's taking all this information now any business being transported the brain well you can see what happens through the great this microbiome affects the brain through vagal stimulation through all the neurotransmitters or metabolites that the bacteria produce as well as these microbial associated molecular patterns are so called Maps so tremendous amount of input coming from the GI tract going to the brain it doesn't surprise us that we can affect the brain we have all kinds you know with what microbiota absent the germ-free animals we see alter associate decreased memory increased stress response cortisol when you give an animal this germ-free LPs stress or shock or put them on a treadmill and run them to you know exhaustion guess what the animals with no bacteria cannot go as long they can not they increase stress respond cortisol ACTH epinephrine norepinephrine I have one out - all those things are altered so again you know it goes on and on what about clinical use of probiotics what can we show there well I think we've got three ways we can do that right we can either resupply beneficial microbes giving probiotics again we got to be careful probiotics is it's not all perfect we can get prebiotics good soluble fibers and now they've shown data that insoluble fibers also affected my microbiome not as dramatic or we can give fecal transplantation which we do in the ICU setting with overwhelming sepsis now and it was c-diff sepsis okay so this look at this study this is done in lung Sweden they took factory workers in the volvo factory that's very interesting and they said okay if you take your break have to factory that join the study will get one red straw which is coated with lactobacillus rudra the other group will get up straw with no coding and if you drink three ounces of your drink we'll give you a free drink during the break but you have to take at least three ounces of a six ounce drink and they follow them for a year that's the only thing they did you got free drink of the break if you join a study okay look at this number of sick days were cut in half pretty dramatic prospective randomized blinded trial how about this trial this is done in kids in New York State okay they gave these kids are four to ten months old you know that their phone might today ages you know if you had kids or nursery school they come home and you get everything they get okay they got placebo air the green they got lactobacilli federal back lactis which is not much of robach tactic provide connectivity if lactobacilli and look at this clinic visits days absent day care antibiotics prescribed the number of antibiotics prescribed during that six months was down seventy percent in those kids now you say well dick come on this is done in new york state where if they're gonna give a kid in nursery school a teacher has to write down if they received antibiotics so that date is pretty solid days absent a little bit gray but if you got antibiotics that clearly shows that because in new york state they had to prove it now here's one you never get a figure when i read this study in 2010 here published in British General Nutrition which is the high quality Journal published 2009 I said give me a break they gave probiotics to high-risk pregnancy remember high-risk pregnancy over women over thirty eight I think it is now coming to high risk clinic the bottom line is about third you see this is a glucose intolerance about thirty six percent of high-risk pregnancies get glucose intolerance during pregnancy during the last trimester so what they did here was he gave probiotics versus control right control group had 36 percent placebo dead probiotics had 34 percent and then active live pro bikes at 13 percent so gestational diabetes you cut by half but just giving pro bikes during last trimester british journal attrition high-quality i still didn't believe it i said i want to see this repeated well guess what that was a landmark study and everybody repeated it and now in the journal maternal phenyl neonatal medicine which is the top journal in the in the area published in 2013 189 articles gestational diabetes reduced miss tastic fast and glutamate Erno fasting glucose decrease preeclampsia CRP all decreased 189 articles that's a meta-analysis thousands of patients recently just published at new zealand 2017 prospective randomized 4:23 significant decrease in gestational diabetes so clearly we're altering inflammatory response in a pregnant woman with this change pretty easy to do inexpensive access what about necrotizing enterocolitis these are babies that are under 4 pounds basically under 7 that 1500 pound or 3 pounds they have about a 20 percent mortality very low birth weight babies they're born so we know whether they die of necrotizing enterocolitis so the concept was let's put back some normal flora these kids have no normal flora they're born and I see basically go right to the ICU on ventilators so what do they do they gave 560 event infants 556 five probiotic four bifida bacteria and they is simulated what a healthy normal baby tried to figure out what they ever go out and put that back in neck 1 from 9 to 5 percent at my hospital now we routinely give our very low birth weight infants bacterial infusions on day 1 life it took me four and a half years to get it through but the Petersons finding starts Daniel maybe there's something to this because there's an overwhelming amount of data now okay what about surgical infections you know 14 trials 50 on a patient's decreased surgical site infections nominator to treat 18 send GI sepsis all these things again I'm not gonna bore you with all these surgical things but this one I want you to look at this study is a landmark study okay nature the best Journal I only wish I had more papers in nature okay it's the kind of thing that wins Nobel Prize okay this is NIH funded national ones US National Institute of Health funded in children per set to prevent sepsis in India which is high risk so these are not sick babies these are healthy babies randomized double-blind placebo-controlled trial lactobacillus plantarum plus fructooligosaccharides 4,000 it's greater than 2,000 grams so this is five pounds and above pretty much all it had at least 35 weeks gestation so these are normal healthy babies okay the Cape this they use w-h-o criteria for sepsis nih-funded they showed 42% reduction in sepsis in these kids remember these are rural India you can't afford big-time medicine lactobacillus plantarum and fructooligosaccharides one week at treatment one dollar forty two percent reduction in sepsis for a dollar a week this has now been repeated with a two thousand patient study in Bangladesh it's ongoing study now in Laos ongoing study I haven't got the results of that yet so we can do this with microbiome changes we can do we don't need these fancy drugs a dollar a week decreasing sepsis so what about seed if we you know we know what causes seed if look at this Jam a 2012 antibiotic associated diarrhea 11,000 patients 60% down decrease in antibody so she'd diarrhea okay what about sea death the first major paper decreasing seed if randomized double-blind placebo-controlled trial British Journal of Medicine British Medical Journal 135 seed f0 vs. 953 that was the first big prospective trial look at this the annals of internal medicine I know the medical residents carries around their pockets best one best journal I know surgeons we don't we we don't read these really good pictures you know but it 4,800 patients basically 4,000 patients whether they find deer 66 percent decrease in see did okay here is a big article just published December 2017 c-diff 1.6 from 3.9 incidents 6,000 patient prospective trial 19 published sir I mean analysis the question was here if you start probe an abaya probiotics today you start on a bike you do not get seed it if you wait three days which is what this study showed timing is key okay but what about this one look at this another study decreased 60% risk the more bacteria you have the more Pro bikes you have the better chance you have this is 6000 patients publishing in this big journal different groups so we've got multiple patients do they worked as at work of you this is where I work here at big Hospital Northwest a big teaching hospital we went from two point two incidents in the ICU people got on our bikes down to 0.7 by just Institute and pro by protocol cost us about 61 cents a day did remember one episode of see tip sepsis hunter grant so you can buy a lot of pro bikes but remember you can't just use any probiotic this is a nice tight ending one where they said okay let's see if we can give yogurt and prevent this okay so they took the most common yogurt sold in England they then screen 17,000 people at 3,000 met criteria and they basically showed c-diff no change because remember it's a strain specific species specific so they've got to have the right species to the effect and I could go on and on about all these studies sepsis seed if ventilator associated pneumonia et cetera but again I won't bore you at that a little bit on prebiotics remember pre bias is a substrate for the bacteria to produce prebiotics or you know these are usually soluble fibers probably ultimate prebiotic is breast milk there's a tremendous amount of prebiotic and breast milk 15 percent 15 percent of the carbohydrate in breast milk cannot be absorbed by the baby you think about that evolutionarily why on earth will revolve to not let the baby absorb this nutrient produced by the mother that nutrient is specifically not absorbed because it wants to make the right bacteria the : to give substrate the Peru's produced increased lactobacillus increased by 30 bacteria so Mother Nature is very smart okay it makes it that way you know the number one killer I do a lot of work in Laos the number one killer in the first six months of life in this world not in the United States but in the world is still diarrhea diseases so it would only make sense that if we give the right formula Mother's Milk it works we now have one protocol where we're giving human milk sugars in the ICU and people have gut failure they come into us after multiple operations so it's a very exciting area and we now know it's not just the soluble fibers but in fact the non fermentable fibers this is in a mouse model of sepsis we can stop and decrease sepsis even with the non fermentable fibers so again you know fibers I can't say enough good things about we now know these multiple papers you can see all 2016-2017 decrease in all cause mortality by a high-fiber diet decreased ieds coronary heart disease decreased cancer etc etc these are very good journals very good articles to show that are they safe the bottom line is the answer is yes we give them in our Hospital everybody transplant liver transplants everybody except bone marrow transplant just God I quit fighting with the ID guys okay there's no data to hurt something but there's no data it helps them we know and liver transplant we decrease sepsis so that was an easy no-brainer of the transplant I said okay we'll do it so I think we've got to start thinking about changing the way we do things by ecological control rather than killing bacteria one of our projects now we just got a big grant from the Nike people Phil Knight from Nike has been very benevolent he lives in Portland he gave us 1 billion dollars studied cancer he gave us four hundred million dollars to study cardiac disease and we've got a big project now going on with us and combined you ergun not me a billion to give the university billion I just wish I had a billion anyway we now combine it we know that if you're in certain beds in our hospital your risk of c-diff is higher this is a skeleton map of our Hospital you don't want to be on 14 K that's where the C dip is so the architects the University of Oregon now are working with what about the that you know remember c-diff is a Spore former spores from c-diff can travel nine meters so we know now we're checking ducks we're checking this we're checking that all over the hospital so that's part of that big project so I think what we can say as I finish up here eat a wide variety of high-fiber foods that will increase your variety okay increase your diversity try to add fermented foods when you can minimize your food additive the sweeteners the stabilizers you know the the emulsifiers the pesticides locate a good source of local probiotics don't spend a lot of money you don't have to spend a lot of money they're not key okay daily intake with a good prebiotic whenever you can hopefully as vegetables and fruits okay remember that watch out with some of these claims a lot of probiotic claims are pure quackery association to disease does not mean a causation we've got to be careful there we remember we got to look at the science we can't just go with some crazy article from some crazy journal remember more bacteria do not automatically mean it's better thank you very much you

Channel: WholisticMatters

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Keywords: inflammation, immune, science, health, nutrition, health and wellness, gut health, gut connection, gut inflammation, wholistic matters, standard process

Id: 41IfdwLqtkA

Length: 59min 24sec (3564 seconds)

Published: Fri Feb 01 2019