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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. All, Al Pater posted this paper [1] on the mortality rates of meat-eaters vs. vegetarians (and vegans) among participates in the EPIC-Oxford study of diet and health. The results were disappointing for us vegans (and vegetarians): There was no significant difference in overall (all-cause) mortality between the diet groups: HRs in low meat eaters, fish eaters, and vegetarians compared with regular meat eaters were 0.93 (95% CI: 0.86, 1.00), 0.96 (95% CI: 0.86, 1.06), and 1.02 (95% CI: 0.94, 1.10), respectively; P-heterogeneity of risks = 0.082. In a separate sub-analysis of the vegan's in the study, they found the same thing - no difference in all-cause mortality between vegans and any of the other diets. Given the distinct longevity advantage for vegans and vegetarians seen in the Adventists Health Study [2], what's the deal with these British vegans and vegetarians? One possible reason is social support. From the demographics in Table 1 of the full text of [1], the UK vegans and vegetarians were significantly less likely to be married or cohabitating than meat eaters (60.8% vs. 75.5%), and less likely to have kids (41.5% vs. 77.2%). Loneliness and social isolation are well-known contributors to ill-health and early mortality. In contrast, from the full text of [2], the Adventist vegans were slightly more likely to be married than the meat-eaters (75.6% vs. 70.3%). In addition, study [3] found the vegetarians and especially vegans in the Epic-Oxford study have significantly lower levels of vitamin B12 than meat-eaters, to the point of outright deficiency: Half of the vegans were categorized as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency. Here is the graph of B12 levels in meat-eaters (open circles at top), vegetarians (closed circles in middle) and vegans (open triangles at bottom): So perhaps it is low B12 and/or other specific vitamin deficiencies among poorly planned diets of the EPIC-Oxford vegan / vegetarian participants that make them more prone to dying than the Adventists. Or perhaps it is simply overall diet quality that is worse in the UK vegans/vegetarians relative to the Adventists that makes them shorter-lived. Here is the table with diet information for the EPIC-Oxford cohort from [1]: As you can see from the highlights in yellow, the vegans/vegetarians aren't much better than the meat eaters in terms of dietary saturated fat, fiber, fruit or vegetable intake. This contrasts markedly with the Adventists dietary data, from [4], shown in tabular form below: Notice among the Adventists, the vegans consumed 50% more fiber and about have the saturated fat compared with the Adventist meat-eaters, and over twice as much fiber as the vegans/vegetarians in the EPIC-Oxford cohort. Unfortunately, the table does not have explicit data on fruit or vegetable consumption, but the fiber numbers and higher Vitamin C numbers of vegans are probably a pretty good indication of higher consumption of fruits/veggies among the vegans. Also notice that B12 intake is actually higher for vegans than for meat-eaters among the Adventist, presumably due to supplementation by the vegans. So overall, it looks the the answer to the question in the title of this post, "Why Don't UK Vegans/Vegetarians Live Longer?", is likely to be that they have much lower overall diet quality than more carefully planned vegan and vegetarian diets, like those of the Adventists, and (hopefully) all of us CR practitioners! This comparison could also be thought of as support for the idea that dietary quality may be as important or more important for health and longevity than dietary quantity (i.e. CR), which I posted about yesterday, and previously in the context of comparing the Okinawans with the Adventists. --Dean ------ [1] Mortality in vegetarians and comparable nonvegetarians in the United Kingdom. Appleby PN, Crowe FL, Bradbury KE, Travis RC, Key TJ. Am J Clin Nutr. 2015 Dec 9. pii: ajcn119461. [Epub ahead of print] PMID: 26657045 Free Article http://ajcn.nutrition.org/content/early/2015/12/07/ajcn.115.119461.long Abstract BACKGROUND: Vegetarians and others who do not eat meat have been observed to have lower incidence rates than meat eaters of some chronic diseases, but it is unclear whether this translates into lower mortality. OBJECTIVE: The purpose of this study was to describe mortality in vegetarians and comparable nonvegetarians in a large United Kingdom cohort. DESIGN: The study involved a pooled analysis of data from 2 prospective studies that included 60,310 persons living in the United Kingdom, comprising 18,431 regular meat eaters (who ate meat =5 times/wk on average), 13,039 low (less-frequent) meat eaters, 8516 fish eaters (who ate fish but not meat), and 20,324 vegetarians (including 2228 vegans who did not eat any animal foods). Mortality by diet group for each of 18 common causes of death was estimated with the use of Cox proportional hazards models. RESULTS: There were 5294 deaths before age 90 in >1 million y of follow-up. There was no significant difference in overall (all-cause) mortality between the diet groups: HRs in low meat eaters, fish eaters, and vegetarians compared with regular meat eaters were 0.93 (95% CI: 0.86, 1.00), 0.96 (95% CI: 0.86, 1.06), and 1.02 (95% CI: 0.94, 1.10), respectively; P-heterogeneity of risks = 0.082. There were significant differences in risk compared with regular meat eaters for deaths from circulatory disease [higher in fish eaters (HR: 1.22; 95% CI: 1.02, 1.46)]; malignant cancer [lower in fish eaters (HR: 0.82; 95% CI: 0.70, 0.97)], including pancreatic cancer [lower in low meat eaters and vegetarians (HR: 0.55; 95% CI: 0.36, 0.86 and HR: 0.48; 95% CI: 0.28, 0.82, respectively)] and cancers of the lymphatic/hematopoietic tissue [lower in vegetarians (HR: 0.50; 95% CI: 0.32, 0.79)]; respiratory disease [lower in low meat eaters (HR: 0.70; 95% CI: 0.53, 0.92)]; and all other causes [lower in low meat eaters (HR: 0.74; 95% CI: 0.56, 0.99)]. Further adjustment for body mass index left these associations largely unchanged. CONCLUSIONS: United Kingdom-based vegetarians and comparable nonvegetarians have similar all-cause mortality. Differences found for specific causes of death merit further investigation. KEYWORDS: diet; mortality; nonvegetarian; vegan; vegetarian -------- [2] [2] JAMA Intern Med.. 2013 Jul 8;173(13):1230-8.. doi: 10.1001/jamainternmed.2013.6473. Vegetarian dietary patterns and mortality in Adventist Health Study 2. Orlich MJ(1), Singh PN, Sabaté J, Jaceldo-Siegl K, Fan J, Knutsen S, Beeson WL, Fraser GE. Author information: (1)School of Public Health, Loma Linda University, Loma Linda, CA 92350, USA. morlich@llu.edu Comment in JAMA Intern Med.. 2014 Jan;174(1):168-9. JAMA Intern Med.. 2014 Jan;174(1):169. JAMA Intern Med.. 2013 Jul 8;173(13):1238-9. Dtsch Med Wochenschr.. 2013 Sep;138(39):1930. IMPORTANCE: Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. OBJECTIVE: To evaluate the association between vegetarian dietary patterns and mortality. DESIGN: Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. SETTING: Adventist Health Study 2 (AHS-2), a large North American cohort. PARTICIPANTS: A total of 96,469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73,308 participants remained after exclusions. EXPOSURES: Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo-vegetarian, and vegan. MAIN OUTCOME AND MEASURE: The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. RESULTS: There were 2570 deaths among 73,308 participants during a mean follow-up time of 5.79 years.. The mortality rate was 6.05 (95% CI, 5.82-6.29) deaths per 1000 person-years.. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs nonvegetarians was 0.88 (95% CI, 0.80-0.97).. The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73-1.01); in lacto-ovo-vegetarians, 0.91 (95% CI, 0.82-1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69-0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75-1.13) compared with nonvegetarians.. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality.. Associations in men were larger and more often significant than were those in women. CONCLUSIONS AND RELEVANCE: Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality.. Results appeared to be more robust in males.. These favorable associations should be considered carefully by those offering dietary guidance. PMCID: PMC4191896 PMID: 23836264 ----------- [3] Eur J Clin Nutr. 2010 Sep;64(9):933-9. doi: 10.1038/ejcn.2010.142. Epub 2010 Jul 21. Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study. Gilsing AM(1), Crowe FL, Lloyd-Wright Z, Sanders TA, Appleby PN, Allen NE, Key TJ. Author information: (1)Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK. BACKGROUND/OBJECTIVES: Vegans, and to a lesser extent vegetarians, have low average circulating concentrations of vitamin B12; however, the relation between factors such as age or time on these diets and vitamin B12 concentrations is not clear. The objectives of this study were to investigate differences in serum vitamin B12 and folate concentrations between omnivores, vegetarians and vegans and to ascertain whether vitamin B12 concentrations differed by age and time on the diet. SUBJECTS/METHODS: A cross-sectional analysis involving 689 men (226 omnivores, 231 vegetarians and 232 vegans) from the European Prospective Investigation into Cancer and Nutrition Oxford cohort. RESULTS: Mean serum vitamin B12 was highest among omnivores (281, 95% CI: 270-292 pmol/l), intermediate among vegetarians (182, 95% CI: 175-189 pmol/l) and lowest among vegans (122, 95% CI: 117-127 pmol/l). In all, 52% of vegans, 7% of vegetarians and one omnivore were classified as vitamin B12 deficient (defined as serum vitamin B12 <118 pmol/l). There was no significant association between age or duration of adherence to a vegetarian or a vegan diet and serum vitamin B12. In contrast, folate concentrations were highest among vegans, intermediate among vegetarians and lowest among omnivores, but only two men (both omnivores) were categorized as folate deficient (defined as serum folate <6.3 nmol/l). CONCLUSION: Vegans have lower vitamin B12 concentrations, but higher folate concentrations, than vegetarians and omnivores. Half of the vegans were categorized as vitamin B12 deficient and would be expected to have a higher risk of developing clinical symptoms related to vitamin B12 deficiency. PMCID: PMC2933506 PMID: 20648045 ------------ [4] J Acad Nutr Diet. 2013 Dec;113(12):1610-9. doi: 10.1016/j.jand.2013.06.349. Epub 2013 Aug 27. Nutrient profiles of vegetarian and nonvegetarian dietary patterns. Rizzo NS, Jaceldo-Siegl K, Sabate J, Fraser GE. Comment in J Acad Nutr Diet. 2014 Feb;114(2):197-8. J Acad Nutr Diet. 2014 Feb;114(2):197. BACKGROUND: Differences in nutrient profiles between vegetarian and nonvegetarian dietary patterns reflect nutritional differences that can contribute to the development of disease. OBJECTIVE: Our aim was to compare nutrient intakes between dietary patterns characterized by consumption or exclusion of meat and dairy products. DESIGN: We conducted a cross-sectional study of 71,751 subjects (mean age=59 years) from the Adventist Health Study 2. Data were collected between 2002 and 2007. Participants completed a 204-item validated semi-quantitative food frequency questionnaire. Dietary patterns compared were nonvegetarian, semi-vegetarian, pesco vegetarian, lacto-ovo vegetarian, and strict vegetarian. Analysis of covariance was used to analyze differences in nutrient intakes by dietary patterns and was adjusted for age, sex, and race. Body mass index and other relevant demographic data were reported and compared by dietary pattern using χ(2) tests and analysis of variance. RESULTS: Many nutrient intakes varied significantly between dietary patterns. Nonvegetarians had the lowest intakes of plant proteins, fiber, beta carotene, and magnesium compared with those following vegetarian dietary patterns, and the highest intakes of saturated, trans, arachidonic, and docosahexaenoic fatty acids. The lower tails of some nutrient distributions in strict vegetarians suggested inadequate intakes by a portion of the subjects. Energy intake was similar among dietary patterns at close to 2,000 kcal/day, with the exception of semi-vegetarians, who had an intake of 1,707 kcal/day. Mean body mass index was highest in nonvegetarians (mean=28.7 [standard deviation=6.4]) and lowest in strict vegetarians (mean=24.0 [standard deviation=4.8]). CONCLUSIONS: Nutrient profiles varied markedly among dietary patterns that were defined by meat and dairy intakes. These differences are of interest in the etiology of obesity and chronic diseases. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved. PMCID: PMC4081456 PMID: 23988511
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