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Microbiome – health & life span

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#61 albedo

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Posted 27 November 2016 - 12:45 PM

Interesting finding on AD and probiotics supplementation on another thread.



#62 normalizing

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Posted 30 November 2016 - 02:08 AM

any comments on this; http://www.nutraingr...ut-health-Study



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#63 albedo

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Posted 30 November 2016 - 09:12 AM

 

Please refer also to Darryl's post. It is on my to read list.
 



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#64 normalizing

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Posted 01 December 2016 - 04:51 AM

its still confusing me, is consuming high protein good at all?


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#65 Darryl

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Posted 01 December 2016 - 05:15 PM

There's a benefit to higher protein diets in increased satiety, which can contribute to weight loss. However high protein diets (think > 18%) are consistently associated with obesity, insulin resistance and diabetes in human epidemiology, and with cancer risk in mid life, but not late life. The emerging association with metabolic disease came as a suprise to me, as one would expect a benefit from satiety. The most consistent element of all longevity extending dietary interventions in animal studies is protein restriction, though restriction of certain amino acids like methionine has a similar benefit.


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#66 Nate-2004

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Posted 01 December 2016 - 05:42 PM

I think it's a lot of guess work to determine which diets and what nutrients are going to feed which members of the microbiome. Oligosaccharides, glutamine and N-A-G, ellagic acid and other things we can consume to benefit say, akkermansia, can also benefit the bad guys if they adapt. I've realized it's kind of difficult to know what's doing what to you much less any general group of the population in terms of diet without constantly taking stool samples and looking at the results.

 

Surely there will be a much more reliable means of determining these things, not to mention a means of either supplementing or changing your gut profile to what's considered beneficial in the near future. Then again, there may not be much profit in it, so companies are not likely putting their R&D there.

 

I don't know about high protein but if I were to guess, what most people benefit from is some kind of balanced diet of fats, carbs and proteins. Go with what makes you feel good throughout the day, that's pretty much the only thing we can go on. Just my opinion of course but Adam Conover said the same thing in his nutrition episode. Personally, I get the least amount of brain fog and the most amount of mental and physical energy from apples & peanut butter, and whole milk yogurt. That's just me though.  If I eat anything that's got fructose without fiber or is high in simple carbs, my brain is gone and I might as well sit the rest of the day out as a lump on a log.  Thing is though, I HATE veggies, I think I have that gene that makes them taste horridly bitter and gag whenever I eat them, the green ones mainly, though carrots can be disgusting too.  I guess somehow I have to balance my enjoyment of life with my health and hope I get the best of both worlds.

 

Is there any effect that exercise has on the microbiome?

 

What about MCT oil? I've been trying that lately but it gives me indigestion, which leads me to believe it's not such a good thing. It does suppress appetite though, like most fats when I eat them. Protein, not so much for me.  I think people may have different responses to food based on their gut profile.


Edited by Nate-2004, 01 December 2016 - 05:43 PM.


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#67 Darryl

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Posted 01 December 2016 - 06:50 PM

We already have the means of inducing a healthy gut microbiome. Avoid unnecessary antibiotics and high fat/protein diets, and seek more fermentable fiber, resistant starch, and polyphenols. Beans, whole grains, raw or retrograded starches from pasta & tubers, greens & deep colored fruit. 

 

When see I persuasive data that a high fat, protein, or refined food consumers have better outcomes than traditional high-starch & fiber / low protein & fat diets centered around sweet potatoes and greens, or corn tortillas + beans, or whole grain pasta + tomatoes, then the field will become much more interesting. Right now I see a lot of supplement consumers and manufactures struggling to justify their past unsubstantiated convictions, and trying to make themselves metabolically sick with unpalatable and ecologically unsustainable diets.


Edited by Darryl, 01 December 2016 - 06:52 PM.

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#68 albedo

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Posted 03 December 2016 - 01:50 PM

 

 

Please refer also to Darryl's post. It is on my to read list.
 

 

 

I gave it a first read. It is very technical and I am not sure I appreciate it all but the conclusions seem aligned with Darryl's comments. Immunity and metabolic health responded in function of balance, mostly protein/carbs:

 

"...Adiposity was primarily driven by total caloric intake (increased in all three dimensions) but was exacerbated on diet compositions with low Prot that promote compensatory feeding. However, the association of health with adiposity was influenced by macronutrient distribution. Health was highest when caloric intake was dominated by Carb; poor cardio-metabolic parameters and shortened lifespan resulted when Prot or Fat dominated intake. Mice in the region of highest Prot intake showed the attributes of immunosenescence (Claesson et al., 2012), and Prot intake far more strongly affected relative levels of CD4 and CD8 lymphocytes than any other macronutrient, suggesting high Prot diets will pre-dispose to altered immuno-regulatory states (Le Couteur et al., 2015). Reconciling these outcomes with the microbiome responses gives a model for diet-host-microbiome interaction ..." (bold mine)

 

Holmes AJ, Chew YV, Colakoglu F, et al. Diet-Microbiome Interactions in Health Are Controlled by Intestinal Nitrogen Source Constraints. Cell Metab. 2016;

 

The second paper Darry mentioned in his post (some of the same authors) points to humans studies too. I find interesting the comment on protein increased needs in the later stages of life:

 

"...High-protein diets are recommended for older people to manage sarcopenia, and we noted a positive relationship between protein intake, body lean, and bone mineral density. On the other hand, epidemiological studies have shown that low-protein, high-carbohydrate diets are associated with improved health in humans (Floegel and Pischon, 2012; Lagiou et al., 2012), which is consistent with our overall conclusions..." (bold mine)

 

Solon-biet SM, Mcmahon AC, Ballard JW, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014;19(3):418-30.



#69 Oakman

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Posted 03 December 2016 - 03:46 PM

 

 

 

Please refer also to Darryl's post. It is on my to read list.
 

 

 

I gave it a first read. It is very technical and I am not sure I appreciate it all but the conclusions seem aligned with Darryl's comments. Immunity and metabolic health responded in function of balance, mostly protein/carbs:

 

"...Adiposity was primarily driven by total caloric intake (increased in all three dimensions) but was exacerbated on diet compositions with low Prot that promote compensatory feeding. However, the association of health with adiposity was influenced by macronutrient distribution. Health was highest when caloric intake was dominated by Carb; poor cardio-metabolic parameters and shortened lifespan resulted when Prot or Fat dominated intake. Mice in the region of highest Prot intake showed the attributes of immunosenescence (Claesson et al., 2012), and Prot intake far more strongly affected relative levels of CD4 and CD8 lymphocytes than any other macronutrient, suggesting high Prot diets will pre-dispose to altered immuno-regulatory states (Le Couteur et al., 2015). Reconciling these outcomes with the microbiome responses gives a model for diet-host-microbiome interaction ..." (bold mine)

 

Holmes AJ, Chew YV, Colakoglu F, et al. Diet-Microbiome Interactions in Health Are Controlled by Intestinal Nitrogen Source Constraints. Cell Metab. 2016;

 

The second paper Darry mentioned in his post (some of the same authors) points to humans studies too. I find interesting the comment on protein increased needs in the later stages of life:

 

"...High-protein diets are recommended for older people to manage sarcopenia, and we noted a positive relationship between protein intake, body lean, and bone mineral density. On the other hand, epidemiological studies have shown that low-protein, high-carbohydrate diets are associated with improved health in humans (Floegel and Pischon, 2012; Lagiou et al., 2012), which is consistent with our overall conclusions..." (bold mine)

 

Solon-biet SM, Mcmahon AC, Ballard JW, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab. 2014;19(3):418-30.

 

 

So, if I understand, we can live a long, fat life, eating a lot of carbs, albeit with the chance of sarcopenia (muscle wasting disease)... or we can live a shorter, unhealthier life, eating more protein, less carbs? That's quite the choice.



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#70 Oakman

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Posted 03 December 2016 - 04:06 PM

Do Microbes in the Gut Trigger Parkinson’s Disease?

http://www.alzforum....kinsons-disease

 

Seems the little buggers selectively "enhance" Parkinson's disease in those so inclined to develop it, but not healthy peps.



#71 Darryl

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Posted 03 December 2016 - 04:28 PM

Plovier et al, 2016. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic miceNature Medicine.

Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition1234567. We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications8. However, the underlying mechanisms of this protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to oxygen and the presence of animal-derived compounds in its growth medium currently limit the development of translational approaches for human medicine9. We have addressed these issues here by showing that A. muciniphila retains its efficacy when grown on a synthetic medium compatible with human administration. Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its capacity to reduce fat mass development, insulin resistance and dyslipidemia in mice. These improvements were notably associated with a modulation of the host urinary metabolomics profile and intestinal energy absorption. We demonstrated that Amuc_1100, a specific protein isolated from the outer membrane of A. muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used for pasteurization, improves the gut barrier and partly recapitulates the beneficial effects of the bacterium. Finally, we showed that administration of live or pasteurized A. muciniphila grown on the synthetic medium is safe in humans. These findings provide support for the use of different preparations of A. muciniphila as therapeutic options to target human obesity and associated disorders.


#72 normalizing

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Posted 03 December 2016 - 08:56 PM

i wonder how microbes deal with eating insects. insects are high protein but surprisingly the outer shell is high fiber food too



#73 albedo

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Posted 09 December 2016 - 11:56 AM

Very interesting study which I think should be considered when taking antibiotics (AB), mostly for long-term usage, due to the possible hepatotoxicity that long-term AB treatments might be causative of. I am interested to look at split doses of both supplemental probiotics but also food sources along the day, both enough away from the AB intake, and somehow helping reproducing the healthy control case of the study.

 

"Diurnal oscillations in microbial localization and metabolite production in the gut have a major impact on the circadian epigenetic and transcriptional landscape of host tissues, not only locally, but also at distant sites such as the liver"

 

Highlights

  • Intestinal microbiota biogeography and metabolome undergo diurnal oscillations
  • Circadian oscillations of serum metabolites are regulated by the microbiota
  • Microbiota rhythms program the circadian epigenetic and transcriptional landscape
  • The microbiota regulates the circadian liver transcriptome and detoxification pattern

Attached File  Microbiome time oscillations.PNG   328.68KB   2 downloads

 

 

Thaiss CA, Levy M, Korem T, et al. Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations. Cell. 2016;167(6):1495-1510.e12.


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#74 Richard McGee

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Posted 09 December 2016 - 10:44 PM

...in the human gut no specific bacterial strains persist in dominant numbers over time and that there is a dynamic equilibrium of functionally redundant bacterial and viral strains that continuously substitute each other in a “kill-the winner” fashion, thereby maintaining stable metabolic potential and taxonomical diversity.

 

link

 

One way of tilting the balance in your favor is a practicing a primarily plant-based diet (emphasizing fermentable fiber). This promotes beneficial flora, but what about the not-so-beneficial flora?

 

One possible intervention is the use of phage technology to selectively attack the non-beneficial gut bacteria, which should allow beneficial flora to gain a stronger foothold. One example I'm aware of is LEF's Florassist GI with Phage Technology.



#75 normalizing

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Posted 10 December 2016 - 07:20 PM

a lot of positive about the benefits of taking probiotics, but why do i always get tired and bloated from taking them?



#76 albedo

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Posted 11 December 2016 - 05:46 PM

a lot of positive about the benefits of taking probiotics, but why do i always get tired and bloated from taking them?

 

Just few thoughts as I am not a doctor...

 

First how about consulting with your GP or a good gastroenterology doctor? Why waiting in case there is an underlying condition? A simple stool microbiology analysis completed with other standard blood tests might be good to check health and in particular the status of your microbiota.

 

Which is your age? Are you suffering of other condition? Which is your diet? Are you eating enough vegetables foods and fibers? Are you under medication? Diet is key: the microbiome is modified, in a highly individualized way, by our diets, metabolic status and the drugs we use and vice versa it can regulate metabolism and drug response. There is a lot going on personalized nutrition and health using sophisticated “omics” profiling, see also the personalized nutrition thread

 

Changing manufacturers and strains could help. Also, ramp up the doses.

 

Typically symptoms are temporary after taking probiotics, I recollect me suffering the same but they subsided rapidly. My first stool microbiology test did indeed show anomalies as I was not eating right.

 


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#77 normalizing

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Posted 12 December 2016 - 05:06 AM

stool microbiology? first i ever hear of this. i didnt know now days people can test anything with stools maybe im outdated. so a gastroenterology doctor can do this? mind me asking, what anomalies were found in your stool and how did you fix



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#78 albedo

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Posted 13 December 2016 - 04:19 PM

stool microbiology? first i ever hear of this. i didnt know now days people can test anything with stools maybe im outdated. so a gastroenterology doctor can do this? mind me asking, what anomalies were found in your stool and how did you fix

 

I think your GP can order one. If I had to re-do today I would try the Genova’s GI Effects® Comprehensive Stool Profile.

 

I did not pass such a comprehensive test but a less detailed still with Genova at distance of 5 years from each other because of no particular symptoms.

 

In the first test they found relatively low but still acceptable levels of beneficial lactobacilli but a bit low bifidobacteria, both of which I guess are quite easy to fix with changes in the diet and supplementation in normal conditions. More worrisome was the presence of some potentially pathological species such as morganella morganiii and Enterobacter cloacae.

 

After quite simple changes in the diet and regular supplementation the second test did show potentially pathological species disappeared and high levels of beneficial ones.

I am not sure of the cost or availability in your Country as I did it as a part of a general check-up package. Let us know if you decide a try.



#79 normalizing

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Posted 14 December 2016 - 02:20 AM

yeh you are in europe its different there with all those tests. i even heard in germany doctors can actually test your neurotransmission levels like dopamine, serotonin etc. before they prescribe anything which is amazing but absolutely unheard of here in US. i assume its going to sound strange too when i ask the doctor about stool microbiology... in fact, im certain it wont work.

 

but is it really necessary to do such a test?

assuming i might have some bad species like you did, wouldn't it be wise to just do what you did without testing for it and see how it goes supposely helping as it helped you?

i have to ask, how did you feel after you got rid of the bad species?

and what changes in diet did you do to alter them in such positive manner, were they feeding on specific food you were consuming before you made the change?



#80 albedo

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Posted 14 December 2016 - 12:04 PM

Hazy, I think Darryl put it short and nice "We already have the means of inducing a healthy gut microbiome. Avoid unnecessary antibiotics and high fat/protein diets, and seek more fermentable fiber, resistant starch, and polyphenols. Beans, whole grains, raw or retrograded starches from pasta & tubers, greens & deep colored fruit." I would like to have a mechanistic answer to your questions but not savvy enough unfortunately. In general I do not hesitate to consult when feeling something wrong (as the fatigue and bloating you report) and agree to keep it simple.



#81 normalizing

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Posted 15 December 2016 - 09:26 PM

yes but from what i see as this recent article; http://www.medicalne...cles/314708.php its actually opposite, avoiding any of the things you mention and not grow your bacteria that actually helps starve cancer



#82 albedo

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Posted 21 December 2016 - 05:21 PM

On the epigenetics effects of gut microbiota, far reaching in the body:

 

"As we move away from plant-based diets, we may be losing some of that communication between microbes and host," notes Rey. "With a Western-type diet, it seems like the communication between microbes and host gets lost."

https://www.eurekale...w-gmc111816.php


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#83 albedo

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Posted 29 December 2016 - 10:20 AM

From Sven Bulterijs blog on LongeCity:

 

The gut microbiome in health and disease

http://www.longecity...th-and-disease/


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#84 normalizing

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Posted 30 December 2016 - 05:02 AM

one thing that confuses me as to how garlic exerts its beneficial effects considering its one of the most potent natural antibiotics. i saw several reports of killing both negative and positive bacteria in the body, but then again, its quite good against various illnesses



#85 albedo

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Posted 30 December 2016 - 05:58 PM

Hazy, IMHO there is a difference between antibiotics and their mode of action (both bactericidal and bacteriostatic) and the antimicrobial activity which several compounds, carried in foods which co-evolved with us, exhibit.

 

Antibiotics, e.g. broad spectrum, possibly act indiscriminately in their bactericidal activity (e.g. interfering with bacterial cell wall). The milder antimicrobial activity of garlic and its sulfur compound allicin has been shown to act selectively on gut bacteria (e.g. clostridum species vs lactobacilli) which might help shifting gut microbiota toward a healthier profile thus generating a cascade of positive effects.

 

Also, the broad range of garlic benefits which seems helping with major diseases, going from cardiovascular diseases to diabetes and even cancer, would indicate that the mechanisms of action are likely differentiated and only partially related to its antimicrobial activity.

 

Moreover, garlic provides a good source of pre-biotics for the health of the gut microbiota, e.g. inulin and FOS, next to other foods such as artichokes, onions, chicory, leeks and bananas. Pre-biotics stimulate the preferential growth of bacteria especially the beneficial lactobacilli and bifidobacteria and more than pro-biotics interventions seem beneficial to steer the microbiota health by providing the necessary food to the lower intestinal tract vs the upper part, the latter privileged in our common western diets. This last point also probably connects to what found earlier (see my previous post) on our western diets possibly disrupting the communication microbiome-host: if in addition to starving the microbiota by cutting their main food sources our diets also disrupt the microbiome host gene expression through the epigenome, then disease is likely to occur.

 

Happy New Year 2017

 

Quigley EM. Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies. Gastroenterol Clin North Am. 2011;40(1):207-22.

 

Maukonen, J. and Saarela, M. (2015) ‘Human gut microbiota: does diet matter?’, Proceedings of the Nutrition Society, 74(1), pp. 23–36. doi: 10.1017/S0029665114000688.

 

Filocamo A, Nueno-palop C, Bisignano C, Mandalari G, Narbad A. Effect of garlic powder on the growth of commensal bacteria from the gastrointestinal tract. Phytomedicine. 2012;19(8-9):707-11.

 

Potential Health Benefits of Garlic (Allium Sativum): A Narrative Review. Journal of Complementary and Integrative Medicine. Volume 5, Issue 1, ISSN (Online) 1553-3840, January 2008

 

Bengmark S. Gut microbiota, immune development and function. Pharmacol Res. 2013;69(1):87-113.

 

(edit: adding reference)
 

 

 

 

 

 


Edited by albedo, 30 December 2016 - 06:05 PM.

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#86 Darryl

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Posted 30 December 2016 - 07:49 PM

@hazy: its worth noting that the human microbiome coevolved with us during millions of years of plant underground storage organ consumption, which probably included varieties of wild Allium bulbs. Ie, While some garlic compounds are indeed fairly universal antimicrobials, they may still favor beneficial species through differential tolerance at normal exposures.

 

Two studies of note: First, a recent study by the Sonnenbergs that demonstrates multigenerational loss of microbes with Western/refined diets. Of note, those Allium vegetables are major dietary sources of microbiota-accessible fructoligosaccharides (fructans)

 

Sonnenburg et al, 2016. Diet-induced extinctions in the gut microbiota compound over generationsNature529(7585), pp.212-215.

The reduced diversity of the gut microbiota in Western populations compared to that in populations living traditional lifestyles presents the question of which factors have driven microbiota change during modernization. Microbiota-accessible carbohydrates (MACs) found in dietary fibre have a crucial involvement in shaping this microbial ecosystem, and are notably reduced in the Western diet (high in fat and simple carbohydrates, low in fibre) compared with a more traditional diet. Here we show that changes in the microbiota of mice consuming a low-MAC diet and harbouring a human microbiota are largely reversible within a single generation. However, over several generations, a low-MAC diet results in a progressive loss of diversity, which is not recoverable after the reintroduction of dietary MACs. To restore the microbiota to its original state requires the administration of missing taxa in combination with dietary MAC consumption. Our data illustrate that taxa driven to low abundance when dietary MACs are scarce are inefficiently transferred to the next generation, and are at increased risk of becoming extinct within an isolated population. As more diseases are linked to the Western microbiota and the microbiota is targeted therapeutically, microbiota reprogramming may need to involve strategies that incorporate dietary MACs as well as taxa not currently present in the Western gut.

 

 

 

Spanking new study that might be of interest to CRON practicioners.

 

Griffin et al, 2016. Prior dietary practices and connections to a human gut microbial metacommunity alter responses to diet interventions. Cell Host & Microbe. http://dx.doi.org/10...hom.2016.12.006

 

We identified dietary practice (DP) associated gut bacterial taxa in individuals either practicing chronic calorie restriction with adequate nutrition (CRON) or without dietary restrictions (AMER). When transplanted into gnotobiotic mice, AMER and CRON microbiota responded predictably to CRON and AMER diets but with variable response strengths. An individual’s microbiota is connected to other individuals’ communities (“metacommunity”) by microbial exchange. Sequentially cohousing AMER-colonized mice with two different groups of CRON-colonized mice simulated metacommunity effects, resulting in enhanced responses to a CRON diet intervention and changes in several metabolic features in AMER animals. This response was driven by an influx of CRON DP-associated taxa. Certain DPs may impair responses to dietary interventions, necessitating the introduction of diet-responsive bacterial lineages present in other individuals and identified using the strategies described.

 

Americans consuming unrestricted diets maintained less diverse fecal microbiota than those of individuals adhering to a plant-rich diet with restricted caloric intake. Moreover, the AMER individuals’ gut communities were marked by a lack of many bacterial lineages that are indicators of the CRON DP.

 
When transplanted into gnotobiotic mice and faced with a CRON diet intervention, some of these less diverse AMER communities mounted community reconfigurations that were weaker than those of their CRON counterparts. By placing these AMER communities into a model metacommunity composed of several CRON communities, we were able to utilize the dispersal of organisms between coprophagic mice to enhance the reconfiguration of an AMER individual’s microbiota in response to a CRON diet intervention. The current study illustrates a way of characterizing the extent to which bacterial dispersal under the most permissive conditions (cohousing of coprophagic mice) impacts diet responses.

 

 

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#87 normalizing

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Posted 30 December 2016 - 10:02 PM

ok thank you for this in depth look on garlic. i also read few articles describing garlic as pro-biotic but then it didnt make sense to me why would it be so when its antimicrobial. i found out through simple google searches that its not the case, especially in vitro showing it kills all positive bacteria (not sure exact mechanism in vivo if any) but i did figure why someone would claim its probiotic. yes, it contains inulin and FOS (like leeks onions etc.) BUT it seems when cooked the antimicrobial effect is gone and its probiotic effect is evident, but not raw!



#88 albedo

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Posted 17 January 2017 - 10:23 PM

Interesting paper with a rich references list on the beneficial effect of high-amylose starches (HAS) foods in terms of elderly healthspan, driving beneficial microbiota, upregulating genes involved in xenobiotic metabolism and in mimicking CR:

 

Keenan MJ, Marco ML, Ingram DK, Martin RJ. Improving healthspan via changes in gut microbiota and fermentation. Age (Dordr). 2015;37(5):98.

https://www.ncbi.nlm...pubmed/26371059

 

"Dietary resistant starch impact on intestinal microbiome and improving healthspan is the topic of this review. In the elderly population, dietary fiber intake is lower than recommended. Dietary resistant starch as a source of fiber produces a profound change in gut microbiota and fermentation in animal models of aging. Dietary resistant starch has the potential for improving healthspan in the elderly through multiple mechanisms as follows: (1) enhancing gut microbiota profile and production of short-chain fatty acids, (2) improving gut barrier function, (3) increasing gut peptides that are important in glucose homeostasis and lipid metabolism, and (4) mimicking many of the effects of caloric restriction including upregulation of genes involved in xenobiotic metabolism."

 

Attached File  HAS and DR.PNG   42.69KB   0 downloads

 

 

 



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#89 normalizing

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Posted 18 January 2017 - 02:15 AM

i wonder what role bacteria plays in addiction to alcohol. ive noticed at first whatever my diet and lack of alcohol caused in changes in microbiota, they dont enjoy alcohol at all making me sick at first and not liking alcohol. BUT over time alcohol becomes more enjoyable and addictive and its opposite thing, actually the newly altered microbiota seems to prefer alcohol and it makes me sick when i dont provide it. very interesting observation but im pretty sure nobody ever researched this yet :S



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#90 normalizing

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Posted 18 January 2017 - 04:27 AM

here is something related i read today by chance; http://www.medicalne...ases/315292.php







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