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Dean Pomerleau

Finally Some Useful Insights about Gut Bacteria and Health

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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  :)xyz 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!   :)xyz

 

--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.

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Here is a new study [1] of the gut microbiota of centenarians in China. Another alphabet soup of bacteria I didn't recognize, with some being elevated and some being reduced in this long-lived population:

 

The results revealed the abundance of Roseburia and Escherichia was significantly greater, whereas that of Lactobacillus, Faecalibacterium, Parabacteroides, Butyricimonas, Coprococcus, Megamonas, Mitsuokella, Sutterella, and Akkermansia was significantly less in centenarians at the genus level.

 

<snip>

 

... diet-related [bacteria] were classified as Bacteroidales, Lachnospiraceae , and Ruminococcaceae . The former two were deceased, whereas the later one was increased, in the high-fiber diet. The age and high-fiber diet were concomitant with changes in the gut microbiota of centenarians, suggesting that age and high-fiber diet can establish a new structurally balanced architecture of gut microbiota that may benefit the health of centenarians.

 

So it looks like the gram-negative, non-butyrate-producing Bacteroides (that I discussed above as potentially pro-inflammatory) are reduced in centenarians, especially those eating a high-fiber diet and this may be beneficial for their health.

 

--Dean

 

--------------

[1] Journal of Microbiology and Biotechnology (2015), 25 (8) The Korean Society for Applied Microbiology and Biotechnology. doi:10.4014/jmb.1410.10014

 

Gut Microbiota Community and Its Assembly Associated with Age and Diet in Chinese Centenarians

 

Wang, F. , Yu, T. , Huang, G. , Cai, D. , Liang, X. , Su, H. , Zhu, Z. , Li, D. , Yang, Y. , Shen, P. , Mao, R. , Yu, L. , Zhao, M. , & Li, Q. .  

 

Abstract

Increasing evidence suggests that gut microbiota underpin the development of health and longevity. However, our understanding of what influences the composition of this community of the longevous has not been adequately described. Therefore, illumina sequencing analysis was performed on the gut microbiota of centenarians (aged 100-108 years; RC) and younger elderlies (aged 85-99 years; RE) living in Bama County, Guangxi, China and the elderlies (aged 80-92 years; CE) living in Nanning City, Guangxi, China. In addition, their diet was monitored using a semiquantitative dietary questionary (FFQ 23). The results revealed the abundance of Roseburia and Escherichia was significantly greater, whereas that of Lactobacillus, Faecalibacterium, Parabacteroides, Butyricimonas, Coprococcus, Megamonas, Mitsuokella, Sutterella, and Akkermansia was significantly less in centenarians at the genus level. Both clustering analysis and UniFraq distance analysis showed structural segregation with age and diet among the three populations. Using partial least square discriminate analysis and redundancy analysis, we identified 33 and 34 operational taxonomic units (OTUs) as key OTUs that were significantly associated with age and diet, respectively. Age-related OTUs were characterized as Ruminococcaceae, Clostridiaceae, and Lachnospiraceae, and the former two were increased in the centenarians; diet-related OTUs were classified as Bacteroidales, Lachnospiraceae , and Ruminococcaceae . The former two were deceased, whereas the later one was increased, in the high-fiber diet. The age and high-fiber diet were concomitant with changes in the gut microbiota of centenarians, suggesting that age and high-fiber diet can establish a new structurally balanced architecture of gut microbiota that may benefit the health of centenarians.

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I came across this really interesting and detailed article on the mechanisms by which our diet and other factors influence the diversity of our gut microbiome, which in turn impacts our health. Several interesting highlights include:

  • Dietary fiber can increase the diversity of your gut bacteria, but only if you already harbor a variety of species in small numbers. Sometimes kids don't get exposed to their mother's microbiota during the birth process, and this can permanently reduce the diversity of their gut flora.
  • If certain gut bacteria don't get enough fiber to eat, they'll start eating the mucus lining of your colon, which can result in 'leaky gut' and irritable bowel syndrome.

The article is well worth reading.

 

--Dean

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  • If certain gut bacteria don't get enough fiber to eat, they'll start eating the mucus lining of your colon, which can result in 'leaky gut' and irritable bowel syndrome.

 

I read this and thought it might be conjecture as I considered the various possible mechanisms for why this could be the case. I thought it more likely that the mucus would degrade for other reasons, which while very likely in itself turns out not to be the only contributor. In 2013 some researchers finally got direct proof of mucous-eating bacteria!

 

Science Daily: On the trail of mucus-eaters in the gut.

http://www.sciencedaily.com/releases/2013/03/130305131036.htm

 

Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing.

http://www.pnas.org/content/110/12/4720

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Here is another good gut microbiome video that Dr. Greger released today, focused on study [1] that compared a vegan and a meat-heavy diet in terms of the gut microbiome profile. 

 

Perhaps not surprisingly, it found rapid changes in the gut microbiome when subjects switched diets. More importantly, it found the vegan diet to result in a much healthier profile, in terms of things like short chain fatty acids (good) and hydrogen sulfide (bad) levels that resulted from the two diets.

 

Once again, it looks like a plant-based diet is the way to go, this time for improved gut health.

 

--Dean

 

------------

[1] Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.

Diet rapidly and reproducibly alters the human gut microbiome.

David LA(1), Maurice CF(2), Carmody RN(2), Gootenberg DB(2), Button JE(2), Wolfe
BE(2), Ling AV(3), Devlin AS(4), Varma Y(4), Fischbach MA(4), Biddinger SB(3),
Dutton RJ(2), Turnbaugh PJ(2).

Comment in
Nat Biotechnol. 2014 Mar;32(3):243-5.

Long-term dietary intake influences the structure and activity of the trillions
of microorganisms residing in the human gut, but it remains unclear how rapidly
and reproducibly the human gut microbiome responds to short-term macronutrient
change. Here we show that the short-term consumption of diets composed entirely
of animal or plant products alters microbial community structure and overwhelms
inter-individual differences in microbial gene expression. The animal-based diet
increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and
Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant
polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii).
Microbial activity mirrored differences between herbivorous and carnivorous
mammals, reflecting trade-offs between carbohydrate and protein fermentation.
Foodborne microbes from both diets transiently colonized the gut, including
bacteria, fungi and even viruses. Finally, increases in the abundance and
activity of Bilophila wadsworthia on the animal-based diet support a link between
dietary fat, bile acids and the outgrowth of microorganisms capable of triggering
inflammatory bowel disease. In concert, these results demonstrate that the gut
microbiome can rapidly respond to altered diet, potentially facilitating the
diversity of human dietary lifestyles.

PMCID: PMC3957428
PMID: 24336217

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Choline seems to be high in animal products and may risk heart clots.
 
 
NATURE | RESEARCH HIGHLIGHTS
CARDIOVASCULAR BIOLOGY
Gut microbes raise heart-attack risk
Nature 531, 278 (17 March 2016) doi:10.1038/531278b
Published online 16 March 2016
http://sci-hub.io/10.1038/531278b
 
Subject terms: Microbiology Cardiovascular biology
 
Gut microbes produce a chemical that enhances clotting in the arteries, increasing the risk of heart attack and stroke.
 
Stanley Hazen of the Cleveland Clinic in Ohio and his colleagues treated human platelets, which form blood clots, with a compound called TMAO. This is made in the body from a waste product of gut microbes, and has been linked to heart disease. The team found that TMAO made the platelets form artery-blocking clots faster. The researchers increased blood TMAO levels in mice by feeding them a diet that was rich in choline, a TMAO precursor, and found that the animals formed clots faster than did those with lower TMAO levels.
 
This effect was not seen in animals that lacked gut microbes or that were treated with antibiotics. When intestinal microbes from mice that produced high levels of TMAO were transplanted into mice with no gut microbes, the recipients' clotting risk increased. The results reveal a link between diet, gut microbes and heart-disease risk, the authors say.
 

Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk.
Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, Li L, Fu X, Wu Y, Mehrabian M, Sartor RB, McIntyre TM, Silverstein RL, Tang WH, DiDonato JA, Brown JM, Lusis AJ, Hazen SL.
Cell. 2016 Mar 9. pii: S0092-8674(16)30113-1. doi: 10.1016/j.cell.2016.02.011. [Epub ahead of print]
PMID: 26972052
http://sci-hub.io/10.1016/j.cell.2016.02.011
 
Abstract
 
Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (n > 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca2+ release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk.

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Perhaps it won't be too long until we start to gain some real insights into the impact of the gut microbiome of health and longevity:

 

Obama administration to launch microbiome initiative, heeding scientists’ calls

 

The new National Microbiome Initiative will start with a federal investment of $121 million in funding from several agencies and will include private support from more than 100 outside organizations, including $100 million over four years from the Bill and Melinda Gates Foundation, according to a White House fact sheet that was posted online on Thursday.

 

--Dean

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Perhaps it won't be too long until we start to gain some real insights into the impact of the gut microbiome of health and longevity:

 

Obama administration to launch microbiome initiative, heeding scientists’ calls

 

The new National Microbiome Initiative will start with a federal investment of $121 million in funding from several agencies and will include private support from more than 100 outside organizations, including $100 million over four years from the Bill and Melinda Gates Foundation, according to a White House fact sheet that was posted online on Thursday.

 

--Dean

 

Wow, that's awesome! I'm often surprised when our government actually does things that matter... :blink: :Pxyz

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All,

 

I opened this thread with an optimistic discussion that studies were starting to converge on useful insights about the link between particularly populations of gut bacteria and health. The data from PMID 10742256 and 24336217, it appeared preferable to me to have an abundance of cellulose-digesting, butyrate-producing firmicutes and a relative dearth of bacteroides, which seemed associated with a meat-heavy diet.

 

But this study [1], posted by Al seems to call that general conclusion into question. What it found was that kids from Burkina Faso (BF) eating a high fiber diet, had just the opposite gut profile, with more bacteroidetes and fewer firmicutes relative to European children who were eating much less fiber. 

 

So it's back to square one for me, i.e. cluelessness about what good gut health looks like in a microbiome profile. It's hard to believe, but gaining useful insights from consumer genetic testing seems much easier than from gut microbiome testing. Hopefully with this new federal initiative (see above), our understanding of the linkage between specific gut microbiome components and health will improve in the not-too-distant future.

 

--Dean

 

--------

[1] Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14691-6. doi:

10.1073/pnas.1005963107. Epub 2010 Aug 2.
 
Impact of diet in shaping gut microbiota revealed by a comparative study in
children from Europe and rural Africa.
 
De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S,
Collini S, Pieraccini G, Lionetti P.
 
Free full text:
 
Abstract
 
Gut microbial composition depends on different dietary habits just as health
depends on microbial metabolism, but the association of microbiota with
different diets in human populations has not yet been shown. In this work,
we compared the fecal microbiota of European children (EU) and that of
children from a rural African village of Burkina Faso (BF), where the diet,
high in fiber content, is similar to that of early human settlements at the
time of the birth of agriculture. By using high-throughput 16S rDNA
sequencing and biochemical analyses, we found significant differences in gut
microbiota between the two groups. BF children showed a significant
enrichment in Bacteroidetes and depletion in Firmicutes (P < 0.001), with a
unique abundance of bacteria from the genus Prevotella and Xylanibacter,
known to contain a set of bacterial genes for cellulose and xylan
hydrolysis, completely lacking in the EU children. In addition, we found
significantly more short-chain fatty acids (P < 0.001) in BF than in EU
children. Also, Enterobacteriaceae (Shigella and Escherichia) were
significantly underrepresented in BF than in EU children (P < 0.05). We
hypothesize that gut microbiota coevolved with the polysaccharide-rich diet
of BF individuals, allowing them to maximize energy intake from fibers while
also protecting them from inflammations and noninfectious colonic diseases.
This study investigates and compares human intestinal microbiota from
children characterized by a modern western diet and a rural diet, indicating
the importance of preserving this treasure of microbial diversity from
ancient rural communities worldwide.
 
PMID: 20679230

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Maybe you are bark-ing up the wrong microbiota tree, Dean.  From your reference above (1) is:

 

Xylanibacter, Prevotella, Butyrivibrio, and TreponemaGenera May Enhance
the Ability to Extract Calories from Indigestible Polysaccharides in BF
Children.
 
Whole grains are concentrated sources of dietary fiber,
resistant starch, and oligosaccharides, as well as carbohydrates
that escape digestion in the small intestine and are fermented in
the gut, producing short-chain fatty acids (SCFAs). Xylanibacter,
Prevotella, Butyrivibrio, and Treponema are exclusive to the BF
children (Fig. S2) and indicate the presence of a bacterial community
using xylane, xylose, and carboxymethylcellulose to produce
high levels of SCFAs (18) whose protective role against gut
inflammation has been well proven (19). These bacteria can
ferment both xylan and cellulose through carbohydrate-active
enzymes such as xylanase, carboxymethylcellulase, and endoglucanase

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Thanks Al,

 

Xylanibacter, Prevotella, Butyrivibrio, and Treponema Genera May Enhance the Ability to Extract Calories from Indigestible Polysaccharides in BF Children.

 

Yes, every new study seems to add to the "Alphabet Soup" of gut bacteria species that may (or may not) be beneficial. All I was saying in my latest post is that there doesn't seem to be much agreement/consensus/convergence on what a healthy gut population looks like, to say nothing of what we can do to promote it. "Eat more fiber" seems to be the only applicable advice, but we knew that all along and for a host of reasons besides feeding our gut bacteria.

 

--Dean

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From Al P. post he quoted:

 

Whole grains are concentrated sources of dietary fiber,
resistant starch, and oligosaccharides, as well as carbohydrates
that escape digestion in the small intestine and are fermented in
the gut, producing short-chain fatty acids (SCFAs). Xylanibacter,
Prevotella, Butyrivibrio, and Treponema are exclusive to the BF
children (Fig. S2) and indicate the presence of a bacterial community
using xylane, xylose, and carboxymethylcellulose to produce
high levels of SCFAs (18) whose protective role against gut
inflammation has been well proven (19). 
 
The BF kids had significantly more SCFA according to the comparative study:
 
"In addition, we found significantly more short-chain fatty acids (P < 0.001) in BF than in EU
children."
 
I found this (full text) overview of SCFA in the gut quite informative and educational:
 
J Lipid Res. 2013 Sep; 54(9): 2325–2340.
doi:  10.1194/jlr.R036012
Gijs den Besten,*† Karen van Eunen,*† Albert K. Groen,*†§ Koen Venema,†** Dirk-Jan Reijngoud,*†§ and Barbara M. Bakker1,

 

Abstract

 

Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism.

 
Keywords: nutritional fiber, bacterial short-chain fatty acid metabolism, short-chain fatty acid fluxes and concentrations
Edited by TomBAvoider

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And this thread started out on such an optimistic and hopeful note...

 

But since that happy beginning, things seem to have just gotten murkier and murkier when it comes to figuring out exactly what makes for a healthy gut microbiome. This new meta-analysis [1] entitled Looking for a Signal in the Noise: Revisiting Obesity and the Microbiome, reinforces how little we know. 

 

They looked across 10 studies investigating the link between obesity and the distribution of bacteria in a person's gut. They basically found no common thread. In this popular press article on the study, one of of the authors says:

 

In the end, we found that there are no clear signatures or predictors of obesity across the microbiome data reported thus far, and that if there is any signature at all, related to diversity of microbes it's not biologically useful. This is a cautionary tale that points to the need to do more work to clarify what we know and don't know.

 

I've previously blabbered on about the ratio of Bacteroides vs Firmicutes (B/F ratio), hoping there might be something there. Nope. From the full text, here is what the authors found:

 

The B/F ratio and the relative abundance of Firmicutes were not significantly associated with obesity in any study.

 

They did find obese folks have slightly less gut microbiome diversity, but even that they don't think means very much:

 

These results indicate that obese individuals do have statistically significantly lower diversity than nonobese individuals; however, it is questionable whether the difference is biologically significant.

 

From the abstract:

 

[W]e directly tested the ability to predict obesity status on the basis of the composition of an individual's microbiome and found that the median classification accuracy is between 33.01 and 64.77%.
 
That might not sound so bad, but the authors go on to say in the full text:
 
The ability to predict obesity status using relative abundance data from the communities was only marginally better than random. These results suggest that given the large diversity of microbiome compositions, it is difficult to identify a taxonomic signal that can be associated with obesity.
 
If someone's gut microbiome can't be used to estimate their current obesity status, it seems even harder to imagine that one's gut microbiome is causing obesity, at least not in any obvious way.
 
The author says:
 

"There really is no one 'healthy' microbiome," says Schloss. "You could look at hundreds of people and they could all have very different populations of microbes in their guts. So the idea that we can correct your microbiome by doing one simple thing also doesn't hold up."

 

That said, generally accepted healthy eating habits that give gut microbes lots of fiber and nutrients to chew on can't hurt, he adds.

 

Oh well, so much for uBiome...
 
--Dean
 
 

----------

[1] MBio. 2016 Aug 23;7(4). pii: e01018-16. doi: 10.1128/mBio.01018-16.

 
Looking for a Signal in the Noise: Revisiting Obesity and the Microbiome.
 
Sze MA(1), Schloss PD(2).
 
Author information: 
(1)Department of Microbiology and Immunology, University of Michigan, Ann Arbor, 
Michigan, USA. (2)Department of Microbiology and Immunology, University of
Michigan, Ann Arbor, Michigan, USA pschloss@umich.edu.
 
 
Two recent studies have reanalyzed previously published data and found that when 
data sets were analyzed independently, there was limited support for the widely
accepted hypothesis that changes in the microbiome are associated with obesity.
This hypothesis was reconsidered by increasing the number of data sets and
pooling the results across the individual data sets. The preferred reporting
items for systematic reviews and meta-analyses guidelines were used to identify
10 studies for an updated and more synthetic analysis. Alpha diversity metrics
and the relative risk of obesity based on those metrics were used to identify a
limited number of significant associations with obesity; however, when the
results of the studies were pooled by using a random-effect model, significant
associations were observed among Shannon diversity, the number of observed
operational taxonomic units, Shannon evenness, and obesity status. They were not 
observed for the ratio of Bacteroidetes and Firmicutes or their individual
relative abundances. Although these tests yielded small P values, the difference 
between the Shannon diversity indices of nonobese and obese individuals was
2.07%. A power analysis demonstrated that only one of the studies had sufficient 
power to detect a 5% difference in diversity. When random forest machine learning
models were trained on one data set and then tested by using the other nine data 
sets, the median accuracy varied between 33.01 and 64.77% (median, 56.68%).
Although there was support for a relationship between the microbial communities
found in human feces and obesity status, this association was relatively weak and
its detection is confounded by large interpersonal variation and insufficient
sample sizes.IMPORTANCE: As interest in the human microbiome grows, there is an
increasing number of studies that can be used to test numerous hypotheses across 
human populations. The hypothesis that variation in the gut microbiota can
explain or be used to predict obesity status has received considerable attention 
and is frequently mentioned as an example of the role of the microbiome in human 
health. Here we assessed this hypothesis by using 10 independent studies and
found that although there is an association, it is smaller than can be detected
by most microbiome studies. Furthermore, we directly tested the ability to
predict obesity status on the basis of the composition of an individual's
microbiome and found that the median classification accuracy is between 33.01 and
64.77%. This type of analysis can be used to design future studies and expanded
to explore other hypotheses.
 
Copyright © 2016 Sze and Schloss.
 
DOI: 10.1128/mBio.01018-16 
PMID: 27555308

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On 8/25/2016 at 9:43 AM, Dean Pomerleau said:

I've previously blabbered on about the ratio of Bacteroides vs Firmicutes (B/F ratio), hoping there might be something there. Nope. From the full text, here is what the authors found:

 

The B/F ratio and the relative abundance of Firmicutes were not significantly associated with obesity in any study.

Looking at the phylum level, which is what a study referring to firmicutes and bacteroides is doing, is not really useful. uBiome goes down to the genus level, which still doesn't differentiate in enough detail to be really actionable (and I don't believe even those who study the subject know enough to draw specific conclusions). But at least it's better than phylum.

Here are some screens from my uBiome results. Note that I consume about 80g of fiber per day, top sources being flax and cacao nibs. At the phylum level, it's all firmicutes. At the genus level, it starts making a little more sense.

Phylum.png.3ae37f39f5cd2c4972075a6922208afa.pngGenus.thumb.png.f509ccf7a82f92e2bd1bf0dab4cd23aa.png

 


And here is how my weight influencing microflora looks.Weight.png.65bd0e2211465e53deaf984052033060.png

 

Predicted functions are also of interest.

1891473053_PredictedFunctions.png.6f8e87edfb812a6a2a53c2d82f0b0545.png

 

Nutrient metabolism by the microflora is also interesting to me. My bacteria seems OK with carbs, less capable with lipids and pretty lazy with amino acids. I am not sure if this is good or bad -- if it means that as a result I absorb less fat and protein, my guess is it's good? I have been concerned that my protein intake seems to be at about 140% of recommended minimum (way above what Longo suggests), despite being a plant-munching almost vegan. So, if my lazy microbes are shoving it all out, it would be reasonable to assume that they are looking after the well being of their host, right?


Carbs.png.b61eb12d9adde1350600b5b7e0f75be1.png

Lipids.png.b45e451228bbeabcf51cbdb0b8db369e.png

1829962515_AminoAcids.png.3371fc0ee1a4c8aa2103cbd7fba1b59e.png

 

Finally, I don't know what to make of the anti-inflammatory properties of my  microflora -- not sure it makes sense to me.

Butyrate.png.bc807386dea56975b6b5ce8c9e07801c.png

Polyamine.png.5f31389bc3b4e7dbd25c42eb92308dbe.png

Propionate.png.f38a65bf23733168c3b3c0839993b4ab.png

Edited by Ron Put

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For those interested, here is a good broad summary of how to interpret one's bioflora test results:

"How to interpret your microbiome results?

Brown et al. (2011) explained how butyrate-producing bacteria protects your gut from inflammation, ulcerative colitis and colorectal cancer. Six main families of firmicutes are known for their ability to convert lactic acid into butyric acid (butyrate). These are Anaerostipes, Flavonifractor, Faecalibacterium, Pseudobutyrivibrio, Roseburia and Subdoligranulum. Butyric acid induces mucin synthesis and tightens the junctions between epithelial cells, thus preventing inflammation and leaky gut syndrome.

Nevertheless, Bacteoridetes like Bacteroides and Alistipes will convert lactic acid into other short-chain fatty acids (SCFAs) like acetic acid, formic acid or propionic acid, which, if present in too large quantities, will damage the lining of the gut, causing inflammation and hyperpermeability of the intestines, leading to autoimmune diseases. So, although Bacteroides and Alistipes are useful and beneficial to digest whole grains and fats, if their proportion exceeds that of the butyrate-producing firmicutes above, it will most probably cause illness. It is therefore important to keep a higher ratio of butyrate-producing bacteria - if possible two or three times more than the Bacteroides and Alistipes. But you also don't want to have too few Bacteroides and Alistipes, as they can also protect you against pathogenic bacteria."

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