[Music] in this video I will discuss satic and protic fermentation and it's important to note that previous to this section we were using whole genome sequencing to identify at the taxonomic level we were using DNA to identify specific microbes and that is what we refer to as taxonomy but in this section we are measuring genes who code for specific functions so before we were identifying the specific microbe and in this function section we aren't identifying specific microbes we are identifying specific functions and what that means is that we are able to capture these functions and these genes who perform specific functions from anyone any microb who produces them so there's been so much research with the microbiome and we know a lot about what microbes are doing but there's still yet so much that hasn't been discovered and if we were just to look at it through the taxonomic lens identifying specific microbes there and then assuming they're performing a specific function we might miss some of these functions so we're taking that out of the equation we're mining the sample for a gene from anyone it doesn't matter which microb it is but if the gene is there that can code for this function then we're going to pick it up so that's a little bit different and that's the difference really between the taxonomy portion of the test and now we're really getting into the function section so the first part of the function section is satic and proteolytic fermentation and here we see a diagram that explains the difference between them this is for educational purposes only this will not change based on your patient results so so satic fermentation is essentially carbohydrate fermentation and proteolitic fermentation is protein fermentation these are basically the opposite satic fermentation happens when bacteria that are usually commensal take fibers carbs from our diet they ferment it they give off byproducts that tend to be a little bit healthier for us a little bit more anti-inflammatory like short Ching fatty acids or lactate whereas with protolytic ferment we usually have microbes who are a little bit more inflammatory pathogenic gram negative take in protein and sometimes fat from our diet ferment it and give off byproducts that we need in small amounts but in large amounts can be a little bit more toxic and of course that is an overgeneralization but that's a good way to start understanding the use of satic and proteolytic fermentation so from proteolytic fermentation we will have metabolites like ammonia and hydrogen sulfide and amines produced one way to use this section before you dive in to each specific marker in these sections is just to take a step back and look overall do we have a lot of proteolitic fermentation if so I would start with the patient's diet is the patient eating a diet that's high in protein and fat and if not how are they digesting their protein and fat you could use it the other way too if there's not a lot of proteic fermentation if it's really low across the board is the patient eating enough food sometimes that's the case patients who are on restricted diets may not even be eating enough to have enough of this prot protein or proteolytic fermentation so that's one way that we can use this we can get a lot of Clues from diet and digestion from this section so the where digestion comes into this is that your digestion should mostly happen above the colon we digestion starts in the mouth we need a lot of stomach acid we need an appropriate level of stomach acid a lot of patients don't have enough stomach acid we need enzymes and bile we need all these processes to occur for proper digestion before the byproducts of that digestion reaches the large intestine or the colon if any of these processes aren't working correctly then your food is not digested very well it ends up in the large intestine undigested and it's basically a buffet for these bacteria they will consume and over ferment the proteins or even the carbs that weren't digested appropriately in the upper digestive system and they'll give off more of these byproducts than we really need so it is a clue if we have a lot of fermentation happening in the colon that maybe we have an issue with ferment with digestion or with diet so let's start with the satic fermentation we are looking at the short chain fatty acids butyrate propionate acetate and we are also looking at lactate and we'll start with how to read this graph pull up my arrow here so this graph is pretty simple once you know what you're looking at we have the healthy relative abundance so this is our healthy population of buttery it usually Falls between 4.8 and 21.8 and that is denoted in this dark green on the x axis so this dark green will fall between 4.8 and 21.8 the patient sample abundance is about 40 so we see that here with the dotted line and if we follow that up that happens to be at the 95 almost 96th percentile anything in the dark green is considered the 25th to the 75th percentile and that is considered most healthy so if it falls out of that range e either lower or higher than the 25th to 75th percentile it'll it'll be flagged as being high as we see here in the red so just a little bit about short chain fatty acids short chain fatty acids are really important for providing energy to the colonocytes the cells of the colon they help to keep inflammation in balance and they are very important for many different metabolic functions I like to look for balance within all these short chain fatty acids so I will scan and you know butat really high here propionates on the higher end but not as high as butyrate acetates a little bit on the higher end too so they're kind of all high but I like to see balance between the three of them I don't like to see any of them really low and the rest of them high and one of the reasons for that is that high acetate paired with low butyrate for example can lead to Fat gain around the liver so you we really need to see balance between them if we talk a little bit about berate our first short chain fatty acid it is produced by many of the species in fromes like ruminococcus and U bacteria and uate is the main fuel for colonocytes if it is low then utilizing more fibers and resistance starches increases its levels of course it's not low here it's high and we can flip back to that for mcatees and ruminococcus in the keystone species in the disbiosis ratio section and see if they were elevated and if so that's probably one of the reasons why but there's other bacteria who produce it to the next one is propionate propionate is mostly produced by bacteroides and here it is within the healthy range but if it is ever really low then I might go back to the bacteroid section and the disbiosis area and see if our bacteroides was really low and if so that's probably one reason why so propionate promotes anic smooth muscle contraction we do find it however elevated in Alzheimer's disease and autism and it can cause brain neurochemistry impairment and increase the level of glutamate so propionates important in balanced levels it is it does provide important functions like promoting anic smooth muscle contraction but when it is elevated then we do see it in some neurocognitive conditions like Alzheimer's and autism the next one is lactate I'm sorry acetate a few examples of producers of acetate are bifido bacteria and acromania acetate is involved in mechanisms that impact appetite regulation and gut satiety hormones we if it is too high it can become a problem we may see that in on non-alcoholic fatty liver disease where gut derived acetate could result in higher lipid accumulation in the liver don't forget that these short chain fatty acids are fats so having elevated short chain fatty acids May negatively impact the liver and last we have lactate lactate is produced by lactic acid producing bacteria Lac lactobacillus and streptococus it plays an important role in immunomodulation and inflammatory modulation and also contributing to the weakly acidic environment in the microbiome we want the colon to be weakly acidic and lactate plays an important role and so do the rest of the short chain fatty acids in addition to being fats they're acids so they will decrease the pH a little bit we want to make sure that lactic or lactate utilizers like lacosa and new bacterium are balanced because they use lactate as substrates for short chain fatty acid production and if we have an overabundance of lactate in the gut it can be toxic and harmful to host tissue and it has been associated with colitis so if lactate is high try reducing simple carbs and increasing resistant starches in galactooligosaccharides so we want the lactate producers and the lactate utilizers to be balanced we actually did a glyphosate study and it showed that when we took the the donor feal sample and exposed it to glyphosate that the glyphosate increased lactate and acetate production and it decreased propionate so another reason we want to see balance here so if you do notice that pattern of having increased lactate and acetate and decreased propionate then you may start asking your patient how often they eat organic because it's likely they have a very conventional diet that might be high in glyphosate and it's causing some imbalances and their short chain fatty acids so going more organic can help to balance out these short chain fatty acids overall the short chain fatty acids and lactate can be balanced by including a variety of fibers and polyphenols in the diet often if they're low it's because our Alpha diversity is low too so as we increase Alpha diversity and increase those keystones who produce short chain fatty acids and feed them well with fibers and polyphenols then we can improve those short chain fatty acid scores moving on to proteolytic fermentation the first marker we're going to look at is polyamines so here we have have polyamines or amines this patience is pretty high at the 82nd percentile that's actually pretty common I think that we have in in the United States we tend to overeat protein possibly and not digest it well sometimes it's not that we're overeating it at all it's that we are not digesting our amines very well and we have an over production of Aman producing bacteria who were gram negative and a little bit more inflammat so Ames are associated with a healthy metabolism and mucosal function proliferation of intestinal epithelial cells and cellular longevity we do need amines but elevated amines are cytotoxic cadaverine which is one type of amine has been shown to increase histamine toxicity and may be associated with ulcerative colitis amines may be elevated with a lot of protein in the diet especially when we have low fiber in take and we have an abundance of protein degrading organisms such as bacteroides or poor digestion next we have p crestle pesle is an aromatic compound that results from fermentation of tyrosine by gut bacteria phenols like P cresol can be cytotoxic it may cause damage to the gut the skin the vascular system and the kidneys and they have been associated with chronic kidney disease and diabetes tyrosine tends to be metabolized to pressol by bacteria such as bacteroides fragilis which is that pathogen we saw earlier on this patient's report as well as fusobacterium and clostridium and P cresol may be elevated when there is an abundance of these bacteria foods that are high in tyrosine a low fiber intake or poor digestion and just for reference foods that are high in tyrosine are a lot of a lot of protein con containing foods so a lot of really common foods like Dairy soybeans red meat chicken nuts eggs beans and whole greens whole grains so a wide variety of foods next we have ammonia ammonia which is another bypro product of amino acid fermentation is mostly derived from glutamine clostridia interacter e fi stacus and fusobacteria are a few ammonia producers so an overgrowth of ammonia producing bacteria paired with excess protein intake and liver or kidney dysfunction may lead to an elevation of ammonia in the blood which is harmful to the brain and liver bacterial strains like h58 that lack uas activity reduce ammonia concentrations in the gut by crowding out ammonia producing bacteria so decreasing glutamine in the diet and increasing consumption of resistant starches and cell cellulose which promote ammonization while using something like hu58 may help improve ammonia levels ammonia is produced a lot of times by pathogens so those bacteria like eoli and fusobacteria are more pathogenic they like a more alkaline environment because those pathogens usually survive there more so they will produce more ammonia and they kind of compete with our commensals because our commensal is like a weakly acidic environment so that production of ammonia is a defense mechanism by them and if we can help to stabilize the pH in the microbiome and those beneficial Comm meils then we can often decrease this ammonia level also keeping in mind that the ammonia from the microbiome will go to the liver and it can create some damage there so do we need to support the liver do we need to protect the liver do we need to do any kind of detoxes to the liver as well when we see ammonia elevated the next marker is hydrogen sulfide we spoke a little bit about hydrogen sulfide in the pathogen section when we saw when we talked about bilophila wadsworthia producing hydrogen sulfide this patient has a very high hydrogen sulfide level I would definitely expect that this patient would have symptoms of having higher hydrogen sulfide so if this patient thinks that they have a lot of food sensitivities if they're complaining a lot about gas and bloating or constipation and diarrhea from what I'm seeing on this report then that hydrogen sulfide production could be playing a very big role in those symptoms hydrogen sulfide is a byproduct of sulfur and hydrogen gas it is produced by bacteria like DL fibrio including that biophilia wadsworthy we talked about proteo bacteria eoli cbella andoba and clostridium elevated hydrogen sulfide will result in gas bloating constipation or diarrhea and it does occur when we have an overabundance of these bacteria paired with a high protein diet that's rich in cysteine or foods that release hydrogen sulfide during digestion like cruciferous vegetables at low concentrations hydrogen sulfide can be protective for the gut barrier but when it is elevated it can damage intestinal epithelial cells and promote intestinal inflammation by inhibiting butyrate synthesis re research has shown that elevated hydrogen sulfide may also play a role in the pathopysiology of Parkinson's disease so we do see it show up in these neurological conditions at really high levels sometimes as well when I see hydrogen sulfide production elevated I will often CR cross reference to see if we have belilia wadsworthia in the pathogen section to off also see if we have DL fabrio showing up in the family section which just is a family of hydrogen sulfide producers the last marker on protolytic fermentation is methane methane is a gas produced by fermentation of ARA so they're not bacteria but they're ARA such as ukara and methane cannot be utilized by human cells so it will accumulate in the intestines causing excess gas and bloating and is link to constipation and intestinal methane overgrowth methanogens May contribute to weight gain by slowing intestinal Transit and impairing gut motility which increases calorie uptake from food in the digestive system so it decreases motility the food just kind of sits there and then we have increased caloric uptake when we do see methane elevated then replacing animal-based protein with plant-based protein sources and supporting motility and digestion May lower methane production if elevated and we've got some other tips and tricks we can share with you also if you see methane and ukara elevated these archa can be very difficult to manage sometimes so you'll want to be sure to check with your consultant on some ticks tricks and tips for methane production okay so that is it for part three of the report walkthrough and I will see you in the next video