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  1. All, As discussed in this thread, research suggests that the gut microbiome can have a dramatic impact on physical, and even mental, health. But the relationship between the gut and health remains pretty murky, and research in the area is still in its infancy. Today everyone's favorite nutrition pundit, Dr. Greger had what I think even his skeptics will agree was a helpful video outlining one mechanistic account of how gut bacteria impact health via their influence on systemic inflammation, which itself has been implicated in most of the diseases of aging. In the video, he suggests that our body has a 'love/hate' relationship with the bacteria in our gut. On the one hand, some bacteria are quite helpful, turning what would otherwise be indigestible food (i.e. fiber) into useful metabolites, like short chain fatty acids that our body can burn as fuel. On the other hand, some bacteria like cholera or e. Coli are quite detrimental to our health, and can sometimes be fatal. So how does our immune system, which is tasked with coping with all these bacteria, handle the job? Specifically, how does it distinguish between the good bacteria which it should ignore and the bad bacteria which it should combat by triggering an inflammatory response? Dr. Greger points to research [see his citations at the bottom of this post] suggesting that the immune system uses the presence of a high level of the short chain fatty acid butyrate as the signal to distinguish between a gut populated with mostly 'good' vs. mostly 'bad' bacteria. More specifically, during our evolutionary heritage, when our ancestors were all eating a very high fiber (> 100g) diet, a healthy gut population would have generated a lot of butyrate, signally 'all clear' to the immune system, which would 'stand down' as a result. But when the gut became overgrown with 'bad' bacteria (which don't produce butyrate), the immune system would notice this lack of butyrate and swing into action, triggering a (systemic) inflammatory response to combat the bad bacteria. The problem is that today, people are eating a crappy, low-fiber, toxin-loaded Western diet, and as a result, even if a person has mostly 'good' bacteria in their gut, the bacteria don't have enough of their food (i.e. fiber) to produce much butyrate. The immune system interprets this lack of butyrate as a sign that the gut is infested with bad bacteria, and so triggers a persistent, systemic inflammatory response in order to fight the (non-existent) threat from the (non-existent) bad bacteria. This permanent inflammatory state in turn leads to all kinds of chronic disease outcomes, from cardiovascular disease, to inflammatory bowel disease, to neurodegenerative diseases like Alzheimer's. That's where Dr. Greger leaves the story, at least in this video. So which types of bacteria (as reported by uBiome) are the 'good', butyrate-producing guys that will signal our immune system that 'all is well'? According to [1]: Eighty percent of the butyrate-producing isolates [from a sample of human gut bacteria] fell within the XIVa cluster of gram-positive bacteria The common gram-positive bacteria reported at the highest level of the uBiome reports is the phylum "firmicutes". From the firmicutes wikipedia entry: The Firmicutes (Latin: firmus, strong, and cutis, skin, referring to the cell wall) are a phylum of bacteria, most of which have Gram-positive cell wall structure. In contrast, the other common high-level phylum of bacteria reported by uBiome are the gram-negative, non-butyrate-producing Bacteroides. From the microbiome wiki entry for Bacteriodes: Bacteroides are gram-negative, non-spore-forming, anaerobic, and rod-shaped bacteria. So overall, to first approximation, it appears preferable to have an abundance of firmicutes and a relative dearth of bacteroides on one's ubiome report of gut bacteria, at least from the perspective of avoiding the ill effects of systemic inflammation by maintaining a high level of butyrate. But it is undoubtedly not quite this simple. In fact I started down a rabbit hole of reading about gut bacteria that I can't entirely make heads or tails of, and that reinforced my belief that researchers a long way from understanding the impact of gut bacteria on human health - see Note 1 below for one such complication. If anyone has a different, better understanding of all of this, and wants to challenge Dr. Greger's account as an oversimplification, I'd love to hear about it! --Dean --------- Note 1: Perhaps paradoxically, vegetarians have been found to have relatively more non-butyrate producing bacteroides in their guts than omnivores, and the resulting relative dearth of energy-harvesting, butyrate-producing firmicutes in vegetarians has been used to explain the leanness of vegetarians compared to omnivores [2]. In other words, the obesogenic gut microbiome profile appears to be a higher ratio of firmicutes to bacteroides, since firmicutes are able to extract more calories from food by turning fiber into the short chain fatty acid butyrate which the body can metabolize for energy. So while firmicutes may be helpful for signalling the immune system that 'all is well' via butyrate production, the resulting abundance of butyrate produced by the firmicutes may increase one's tendency to gain weight by extracting more calories from food. But if this is true, why do firmicute-lacking vegetarians have lower levels of inflammation, and generally better health, than omnivores? Perhaps your average vegetarian doesn't actually eat that much fiber, so they aren't feeding their firmicutes sufficiently... As I said, it is complicated... ----------- [1] Appl Environ Microbiol. 2000 Apr;66(4):1654-61. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Barcenilla A(1), Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, Flint HJ. Author information: (1)Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, United Kingdom. Butyrate is a preferred energy source for colonic epithelial cells and is thought to play an important role in maintaining colonic health in humans. In order to investigate the diversity and stability of butyrate-producing organisms of the colonic flora, anaerobic butyrate-producing bacteria were isolated from freshly voided human fecal samples from three healthy individuals: an infant, an adult omnivore, and an adult vegetarian. A second isolation was performed on the same three individuals 1 year later. Of a total of 313 bacterial isolates, 74 produced more than 2 mM butyrate in vitro. Butyrate-producing isolates were grouped by 16S ribosomal DNA (rDNA) PCR-restriction fragment length polymorphism analysis. The results indicate very little overlap between the predominant ribotypes of the three subjects; furthermore, the flora of each individual changed significantly between the two isolations. Complete sequences of 16S rDNAs were determined for 24 representative strains and subjected to phylogenetic analysis. Eighty percent of the butyrate-producing isolates fell within the XIVa cluster of gram-positive bacteria as defined by M. D. Collins et al. (Int. J. Syst. Bacteriol. 44:812-826, 1994) and A. Willems et al. (Int. J. Syst. Bacteriol. 46:195-199, 1996), with the most abundant group (10 of 24 or 42%) clustering with Eubacterium rectale, Eubacterium ramulus, and Roseburia cecicola. Fifty percent of the butyrate-producing isolates were net acetate consumers during growth, suggesting that they employ the butyryl coenzyme A-acetyl coenzyme A transferase pathway for butyrate production. In contrast, only 1% of the 239 non-butyrate-producing isolates consumed acetate. PMID: 10742256 ------------ [2] Ann Nutr Metab. 2009;54(4):253-7. doi: 10.1159/000229505. Epub 2009 Jul 27. Characterization of bacteria, clostridia and Bacteroides in faeces of vegetarians using qPCR and PCR-DGGE fingerprinting. Liszt K(1), Zwielehner J, Handschur M, Hippe B, Thaler R, Haslberger AG. Author information: (1)Department of Nutritional Sciences, University of Vienna, Vienna, Austria. BACKGROUND/AIMS: This study aimed to investigate the quantitative and qualitative changes of bacteria, Bacteroides, Bifidobacterium and Clostridium cluster IV in faecal microbiota associated with a vegetarian diet. METHODS: Bacterial abundances were measured in faecal samples of 15 vegetarians and 14 omnivores using quantitative PCR. Diversity was assessed with PCR-DGGE fingerprinting, principal component analysis (PCA) and Shannon diversity index. RESULTS: Vegetarians had a 12% higher abundance of bacterial DNA than omnivores, a tendency for less Clostridium cluster IV (31.86 +/- 17.00%; 36.64 +/- 14.22%) and higher abundance of Bacteroides (23.93 +/- 10.35%; 21.26 +/- 8.05%), which were not significant due to high interindividual variations. PCA suggested a grouping of bacteria and members of Clostridium cluster IV. Two bands appeared significantly more frequently in omnivores than in vegetarians (p < 0.005 and p < 0.022). One was identified as Faecalibacterium sp. and the other was 97.9% similar to the uncultured gut bacteriumDQ793301. CONCLUSIONS: A vegetarian diet affects the intestinal microbiota, especially by decreasing the amount and changing the diversity of Clostridium cluster IV. It remains to be determined how these shifts might affect the host metabolism and disease risks. Copyright 2009 S. Karger AG, Basel. PMID: 19641302 Dr Greger Video References: C J North, C S Venter, J C Jerling. The effects of dietary fibre on C-reactive protein, an inflammation marker predicting cardiovascular disease. Eur J Clin Nutr. 2009 Aug;63(8):921-33. J R Goldsmith, R B Sartor. The role of diet on intestinal microbiota metabolism: downstream impacts on host immune function and health, and therapeutic implications. J Gastroenterol. 2014 May;49(5):785-98. S M Kuo. The interplay between fiber and the intestinal microbiome in the inflammatory response. Adv Nutr. 2013 Jan 1;4(1):16-28. J M Harig, K H Soergel, R A Komorowski, C M Wood. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med. 1989 Jan 5;320(1):23-8. D M Saulnier, S Kolida, G R Gibson. Microbiology of the human intestinal tract and approaches for its dietary modulation. Curr Pharm Des. 2009;15(13):1403-14. J Tan, C McKenzie, M Potamitis, A N Thorburn, C R Mackay, L Macia. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91-119. P V Chang, L Hao, S Offermanns, R Medzhitov. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2247-52. R Peltonen, J Kjeldsen-Kragh, M Haugen, J Tuominen, P Toivanen, O Førre, E Eerola. Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet. Br J Rheumatol.1994 Jul;33(7):638-43.
  2. As of today (10/9/15), uBiome is offering a free microbiome test kit to the first 1000 users to download their new iPhone/iPad app, and agree to participate in a study to investigate the connection between the gut microbiome and weight loss. Below is the announcement and instructions. Its a great way to participate in a citizen science project on the important topic of gut health. Hurry while supplies last! --Dean SAN FRANCISCO, CA (PRWEB) OCTOBER 09, 2015 Leading microbial genomics startup uBiome today launched the first-ever microbiome app, in tandem with a study that aims to better understand the relationship between weight management and the microbiome. The study uses the ResearchKit framework, designed by Apple, to gather data more frequently and more accurately from participants using an iPhone app. The uBiome app is available as a free download from the App Store. The first 1,000 users to complete the app’s questionnaire and share a link to the app on social media will receive a free uBiome microbiome testing kit, usually priced at $89. After these free kits have been distributed, users of the app will qualify for a 50% discount. uBiome is the first biotech company to launch a microbiome-focused app on the ResearchKit framework, following in the footsteps of prestigious clinical trailblazers such as Mt. Sinai, the Dana Farber Cancer Institute, Sage Bionetworks, Massachusetts General Hospital, and Stanford Medicine. From asthma, breast cancer and Parkinson’s disease to diabetes and heart health, existing ResearchKit apps are contributing to scientific understanding of serious health conditions around the world. “Being able to see how research participants compare to each other is critical to a deeper understanding of human health and the role played by the microbiome,” says Jessica Richman, co-founder and CEO of uBiome. “Participants have already been incredibly eager to contribute to this exciting new branch of science, and we look forward to this opportunity for greater participation.” uBiome anticipates rapid adoption of its ResearchKit app. Stanford Medicine, one of the first users of the platform, recruited as many research participants in 24 hours as it usually would in a year, with more than 11,000 people signing up within one day. Nearly 75 percent of mobile subscribers in the United States own smartphones and Health & Fitness is the fastest growing app category. Dr. Zachary Apte, CTO and co-founder of uBiome, explains that processing microbiome data has only become possible because of the company’s powerful high-throughput DNA sequencing technology. “uBiome’s free iPhone app connects the phone in your pocket to our powerful technology in the lab, enabling users to directly contribute to enhancing human health through better understanding of the human microbiome.” The human microbiome contains around ten times as many cells as the entire body, and an individual’s bacteria is responsible for between three and six pounds of their weight. To place this in context, an average human brain weighs three pounds. The bacteria, which live in and on the body, play critical roles in human health. Although some kinds of bacteria can be responsible for a host of problems such as autoimmune disorders, diabetes, heart conditions, Inflammatory Bowel Disease and skin conditions, the right types of “friendly bacteria” assist us with digestion and the synthesis of vitamins among other important biological activities. To download the free uBiome ResearchKit iPhone app visit: https://itunes.apple.com/US/app/id998772157. About uBiome Technologists from UCSF, Stanford, and Cambridge launched uBiome in 2012 after a crowd-funding campaign raised over $350,000 from citizen scientists, roughly triple the initial goal. uBiome is now funded by Andreessen Horowitz, Y Combinator, and other leading investors. The company’s mission is to use big data to understand the human microbiome by giving consumers the power to learn about their bodies, perform experiments, and see how current research studies apply to them.
  3. Dean Pomerleau

    The Calorie Controversy

    All, There is a good article out today in the Atlantic on just how difficult it is to accurately calculate the energy value available from food. It talks about how the USDA does it, and how it varies from food-to-food (e.g. almonds & walnuts provide 20-33% fewer calories than expected), and person-to-person depending on one's genetics and microbiome. It talks about eating for satiety rather than targeting a certain calorie level is likely to be more effective for regular people trying to lose weight. Here is a passage I found quite interesting, given my advocacy of fruit: Since 2005, David Wishart of the University of Alberta has been cataloguing the hundreds of thousands of chemical compounds in our bodies, which make up what’s known as the human metabolome... According to Wishart, these chemicals and their interactions affect energy balance. He points to research demonstrating that high-fructose corn syrup and other forms of added fructose (as opposed to fructose found in fruit) can trigger the creation of compounds that lead us to form an excess of fat cells, unrelated to additional calorie consumption. “If we cut back on some of these things,” he says, “it seems to revert our body back to more appropriate, arguably less efficient metabolism, so that we aren’t accumulating fat cells in our body. An interesting article worth reading in its entirety. --Dean
  4. Akkermansia muciniphila Anyone have a mainstream (non-piggy-capitalistically greed-driven) source for this evidently beneficial bacteria? https://knowridge.com/2017/01/immune-system-uses-gut-bacteria-to-control-glucose-metabolism/ Immune system uses gut bacteria to control glucose metabolism January 10, 2017 Researchers at Oregon State University and other institutions have discovered an important link between the immune system, gut bacteria and glucose metabolism – a “cross-talk” and interaction that can lead to type 2 diabetes and metabolic syndrome when not functioning correctly. The findings, published today in Nature Communications, are one example of how different mammalian systems can affect each other in ways not previously understood. A better understanding of these systems, researchers say, may lead to new probiotic approaches to diabetes and other diseases. The research also shows the general importance of proper bacterial functions in the gut and the role of one bacteria in particular – Akkermansia muciniphila – in helping to regulate glucose metabolism. This bacteria’s function is so important, scientists say, that it has been conserved through millions of years of evolution to perform a similar function in both mice and humans. “We’re discovering that in biology there are multiple connections and communications, what we call cross-talk, that are very important in ways we’re just beginning to understand,” said Dr. Natalia Shulzhenko, an assistant professor in the OSU College of Veterinary Medicine, and one of the corresponding authors on this study. “It’s being made clear by a number of studies that our immune system, in particular, is closely linked to other metabolic functions in ways we never realized. This is still unconventional thinking, and it’s being described as a new field called immunometabolism.” “Through the process of evolution, mammals, including humans, have developed functional systems that communicate with each other, and microbes are an essential part of that process.” It had been previously observed that an immune mediator – one type of interferon, or signaling protein called IFN-y – can affect the proper function of glucose metabolism. IFN-y helps fight several pathogens and infections, but a decrease in its levels can lead to improvement in glucose metabolism. However, this actual process has not been understood. “Before this, no one had a clue exactly how IFN-y affected glucose tolerance,” said Andrey Morgun, an assistant professor in the OSU College of Pharmacy and also a corresponding author on the study. “The involvement of microbes had not really been considered. But with the help of a statistical model and an approach we call a transkingdom network, we were able to pinpoint some likely bacterial candidates.” The bacteria A. muciniphila, was found to play a critical role in this communication process – in their study, the scientists called it a “missing link.” Research showed that mice specially bred with reduced levels of IFN-y had higher levels of A. muciniphila, and significantly improved glucose tolerance. When IFN-y levels increased, A. muciniphila levels declined, and glucose tolerance was reduced. Similar observations were also made in humans. It’s been observed, for instance, that athletes who are extremely fit have high levels of the gut bacteria A. muciniphila, which is a mucus-degrading bacteria. The research makes clear that two systems once believed to be functionally separate – immunity and glucose metabolism – are, in fact, closely linked, and the bridge can be provided by gut bacteria. There’s probably more than one bacteria involved in this process of communication and metabolic control, researchers said. The gut harbors literally thousands of microbes that appear to function almost as a metabolically active organ, emphasizing the critical importance of gut bacterial health. Bacteria-mediated communication, of course, is just one part of complex human systems – issues such as proper diet, exercise, and appropriate weight control are all still important, the researchers said.
  5. Sthira

    Poop transplant

    Let's say hypothetically that someone you liked approached you (you = healthy young person) and complained about their unhealthy gut microbiome. You suggested a fecal transplant. All you'd need would be your poop, a blender, a turkey baster, and cajones, right?
  6. Zeta

    µBiome

    µBiome is offering half off their basic sequencing service. I was thinking about doing it but I googled around and found a lot of people wondering how mature the technology - or at least our/their ability to interpret the raw data - is. For example, this article: "Here’s the poop on getting your gut microbiome analyzed". Has anyone gotten their gut microbiome analyzed and learned anything worthwhile, for ex., something "actionable"? Zeta
  7. Thanks to Al Pater for posting the following two articles to our lists: Signatures of early frailty in the gut microbiota. Jackson M, Jeffery IB, Beaumont M, Bell JT, Clark AG, Ley RE, O'Toole PW, Spector TD, Steves CJ. Genome Med. 2016 Jan 29;8(1):8. doi: 10.1186/s13073-016-0262-7. PMID: 26822992 http://www.genomemedicine.com/content/8/1/8 http://www.genomemedicine.com/content/pdf/s13073-016-0262-7.pdf Gut microbiota and aging. O'Toole PW, Jeffery IB. Science. 2015 Dec 4;350(6265):1214-5. doi: 10.1126/science.aac8469. Review. PMID: 26785481 http://science.sciencemag.org.sci-hub.io/content/350/6265/1214.short I sent in my sample to μBiome at the end of November. Still no results.... When I get them I'll report on my "diversity". Zeta
  8. Just received in inbox: Starting right now, a 5-site microbiome testing kit is just $89 instead of the usual $399. Offer valid until Friday at midnight, or while supplies last. Use discount code 5FOR1BF when you checkout at μBiome. Zeta
  9. CRS, Do CRS members have different colon microbiomes? Could Ubiome or American Gut model the CRS gut?http://www.ubiomeblog.com http://humanfoodproject.com/americangut/ A recent article on changes to the gut microbiome of diabetic children. http://www.sciencedaily.com/releases/2015/02/150205123022.htm Could a hydrogen gas test be developed to detect diabetic guts vs CRS guts? http://www.ncbi.nlm.nih.gov/pubmed/11429513 Could hydrogen be traced to bacteria in the diabetic gut? http://www.nejm.org/doi/full/10.1056/NEJM196907172810303 Comparing diabetic vs non-diabetic patients could lead to reducing Medicaid and US medical costs. Could open data model diabetics vs non diabetics? http://www.ubiomeblog.com/surprising-comparison-male-vs-female-microbiomes/#comment-915 Deep Dive is a free Watson like AI from Stanford. Could Deep Dive be used to build a NM diabetes comorbidity model? https://www.quantamagazine.org/20150129-networks-reveal-the-connections-of-disease/ Could we use Deep Dive with Ubiome data to connect diseases? Could CRS members represent a baseline? http://www.eetimes.com/document.asp?doc_id=1324936 http://deepdive.stanford.edu/ I created an expert system that led to shotgun sequencing at the Human Genome Project at Los Alamos. Mycin was developed for bacterial identification. http://en.wikipedia.org/wiki/Mycin Ubiome may be able to create a Mycin/Watson like expert system based on microbiomes and open data? Antibiotics may reduce human colon bacteria? Humans may never recover colon bacteria after antibiotic use? Missing Microbe Book - Antibiotics disrupt gut microbes and may cause chronic diseases/diabetes. http://martinblaser.com Do CRS members represent an Ancestral Microbiome? Can we compare the CRS gut to diabetic guts? http://humanfoodproject.com/ancestral-microbiome/ US chronic disease, 50% of Medicaid funding, is consuming state and federal budgets. Especially in southern states. Austria recently leveraged open data to develop a model of diabetes comorbidity = chronic disease. Quantifying age- and gender-related diabetes comorbidity risks using nation-wide big claims data http://arxiv.org/pdf/1310.7505v1.pdf Can US state Medicaid databases be used to quantify the diabetes vs education problems in the US? Who can partner with State of NM in developing a model of the state budget related to diabetes? Who will build a diabetes comorbidity model for NM? The US? NM DOIT presently manages NM ASPEN project for Medicaid data capture. DOIT Aspen project for HSD/Medicaid ($120 million) - Aspen creates approx 1 Terabyte a month? http://www.hsd.state.nm.us/uploads/FileLinks/6331671b99b34cafba9bd8cb327bc208/2012_11_05_630_ISD_Approved_Imaging_Plan.pdf NM has many chronic disease cost issues. The NM Budget in 2013 spent 39% on health care. NM health care costs grow annually. Is this due to diabetes comorbidity? One third of the US will be diabetic in 2050. Mexico may be worse. http://www.cdc.gov/media/pressrel/2010/r101022.html US Medicaid Surpasses K-12 Spending in US State Budgets and Federal Budgets. Medicaid = diabetes? http://www.decisionsonevidence.com/2012/01/for-state-budgets-medicaid-surpasses-k-12-spending/ A US Budget graphic shows Health replacing Defense spending in 1990's - 2013. Is this caused by diabetes? http://solomonkahn.com/us_budget/ Numbers graphs show US Health Care costs skyrocketing due to obesity. Mexico will be worse. http://nusi.org/the-science/why-nusi/ 40% of US hospital budgets now pay ICU/chronic disease costs. http://money.cnn.com/video/technology/2013/07/24/fortune-trailblazers-icu-telemedicine.fortune NM ICUs are dominated by diabetes. http://www.amazon.com/Where-Night-Is-Day-Politics/dp/080145168X NM Budget in 2013 spent 39% on health care. Health care is growing annually. Change the year at this site and watch health care grow over time. Compare FL at 41%, TX 36%, etc. http://www.usgovernmentspending.com/year_spending_2013NMms_15ms2n#usgs302 CO Budget in 2013 spent 27% on health care. Obesity is a function of education? CO 3rd most educated state. http://www.usgovernmentspending.com/year_spending_2013COms_15ms2n#usgs302 http://www.foxbusiness.com/personal-finance/2012/10/15/americas-best-and-worst-educated-states/ How can state budgets be connected to diabetes? Can education budgets continue to shrink because of diabetes? NM state Medicaid databases may be used to quantify the diabetes costs for NM state legislature? But can Federal databases also be used? HIPAA de-identification in the US may complicate studies of Diabetes Comorbidity? http://med.stanford.edu/irt/security/hipaa.html http://www.hhs.gov/ocr/privacy/hipaa/understanding/coveredentities/De-identification/guidance.html http://www.hhs.gov/ohrp/sachrp/appendixf.html http://hhshipaaprivacy.com/assets/10/resources/Panel5_McGraw.pdf Henry Brown henry.brown@state.nm.us 505 795-3680
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