Tuesday, February 12, 2013

Gut Bacteria Modulation: Ramp Up Your Short-Chain Fatty Acid Production With Fermentable Starches Within 6 Days. Longterm Fat Loss, Gut Health & Cancer Protection Possible

You cannot handpick several billion lodgers in your intestine, but you can attract the right one by providing them with the foods they like. Contrary to the current probiotic hype, the key to gut and metabolic health lies in the prebiotics you are stuffing down your piehole.
It's quite funny, only 5 years ago, everyone was still smiling at people who spent extra bucks on yogurts and other dairy products that were enriched with certain bacteria strains - strains, which were and obviously still are supposed to have health-promoting effects. The fact that probiotic yogurts and similar stuff have meanwhile made it into the store brand line-up of the large discount-markets (at least here in Germany) is however clear cut evidence that the previously laughed at idea that gut bugs are something you want to foster and promote has meanwhile turned into another of those partly highly questionable, but widely accepted pieces of "nutritional wisdom". The question that remains is, will they join the ranks of other scientific hypothesis that have made it n allegedly oversimplified from the bench to the store-boards before their time was ripe? Hypotheses such as the "cholesterol is bad for your heart", the "pasta and rice will keep you lean" and the "fat makes fat" hypotheses?

Don't worry, I am neither going to rant, nor am I suggesting that the whole idea about the importance of the gut microbiome is similarly flawed as the "eat fat and get fat"-hypothesis. The thing I do yet want to point out, before I tell you more about the latest scientific findings, is that our knowledge about the good and the bad guys in our intestines, about the ways they interact and about the short- and longterm effects of these interactions are so limited that my gut tells me (all puns intended) that everything that goes beyond the classics, i.e. the consumption of a diet rich in various types of fibers and a reasonable amount of fermented foods could well turn against us in a not very distant future.

Feeding the good guys: Does it work? And how does it work?

Based on the currently available evidence, it does however in fact look like the shift towards short-chain fatty acid producing bacteria, the scientists from the University of Minnesota and the scientist from the Fred Hutchinson Cancer Research Center initiated in their 20 study participants (ten men and ten women) who had been recruited via flyers around the University campus (that alone goes to tell you how "mainstream" the notion of beneficial gut bacteria has become). The subjects were health and aged between 18 and 60 years, they were non-smokers and were not taking any prescription meds and contrary to the average American (cf. "How Fat We Have Become") their BMIs were in the normal range.
Table 1: Macronutrient composition of the test meal on day 1 and the supplemental cereal bars and beverages the subjects consumed in the course of the 6-day study period on four occasions every day (Klosterbuer. 2013)
"Participants consumed five treatments in a double-blind, cross-over design with treatment periods of 7 d followed by a 21 d washout period. On day 1 of the study, following a 12 h fast, participants arrived at the GCRC and consumed either a low-fibre control breakfast or one of four fibre-containing breakfasts. Meals consisted of a muffin, hot cereal, and fruit-flavoured beverage. For the next 6 d, participants consumed the study products at home. Treatments were provided as cereal bars and a beverage mix, which was pre-measured into 500 ml water bottles. Participants were instructed to consume four cereal bars and one beverage over the course of each day." (Klosterbuer. 2013)
Obviously the test breakfast, as well as the bars and beverages the dietary composition of which you can see in table 1 contained additional "functional" additives. As indicated by the titles above the respective columns in table 1, these were
  • Figure 1: Short-chain fatty acid content of the stools (top), number of stools and consistency (1=hard, 4=diarrhea, middle), gastrointestinal symptoms (bottom, Klosterbuer. 2013)
    for the breakfast, 25 g SCF or RS alone or in combination with 5 g pullulan (SCF+P and RS+P),
  • for the beverages and bars in the treatment groups, 20g SCF or RS alone or in combination with 5 g pullulan (SCF+P and RS+P) for the beverages and bars and
  • for the beverages and bars in the control group, fully digestible maltodextrin
  • the short chain fatty acids (SCF) were produced via hydrolysis of maize starch, followed by
    cooling to form a branched structure, 
  • the resistant starch (RS) was a type 3 (RS3) retrograded starch roduced from heat moisture-treated, high-amylose maize starch, and 
  • pullulan is a linear glucose homopolysaccharide that's formed during the fermentation of dextrin by the yeast Aureobasidium pullulans.
All test products were provided by Tate and Lyle, Inc. and - as you can likewise see in table 1 matched for macronutrient and energy content. All bars and beverages were meant to be consumed along with participants regular diets.

Astrology was yesterday, feceology (=poopology ;-) is the future!

Aside from the obligatory protocols on the state of their digestive health the subjects also had to collect stool samples, which were then analyzed by the researchers who were looking at the RNA and DNA content of the samples to identify any changes in the makeup of the gut microbiom, without exact quantification of individual strains. What they found was that ...
"[a]mong the treatments, the control was significantly different from the SCF (P<0.001) and SCFþP(P<0.0002) treatments. The SCF treatment was significantly different from the RS treatment (P<0.007), and the SCF+P treatment was significantly different from the RS+P treatment (P<0.002). The GMC [gut microbial community] following the consumption of the SCF and SCF+P treatments was not significantly different." (Klosterbuer. 2013)
Now this certainly does not sound very informative, right? It in fact isn't but let's be honest, what's the additional value of me telling you that the scientists were able to associate a certain peak in the bacterial make up with either Anaero-coccus vaginalis or Parabacteroides goldsteinii and another one with either Parabacteroides distasonis or Parabacteroides merdaeusing anisilico?  Not much, right.

"I know that we know nothing" An adequate description of the "state of the art"

My casual observation that knowing the funky names of the individual bacteria that felt specifically cosy in the acidified short-chain fatty acid loaden milieu that formed in response to the dietary intervention is about as useful to you as knowing all the names of the tiny insects in the Amazon Delta. In view of the fact that this is not much different for the scientists who were not even able to tell exactly which bugs they were looking at here. In fact, we have not even come so far to say "little do we know" - the current state of our "understanding" of the complexity of the gut microbiom is simply far from allowing any reliable prognosis statements on which bacteria we want in which ratios.
Figure 2 (first published in "Waxy Maize Reloaded"): Changes in postprandial energy expenditure (left) and fatty acid oxidation (right) after the ingestion of regular and WM-HPD pancakes (data adapted from Shimotoyodome. 2011)
That being said the net increase in SCFA production that was achieved by all treatments in the study at hand is an endpoint that may provide at least some orientation. After all, you will probably all remember the impressive results of theh Shimotoyodome study from 2011 (see figure 2) I discussed in conjunction with the post on WM-HDP, back in the day. While this is likewise still speculative, it's still highly likely that the increase in fatty acid oxidation the researchers observed in their human subjects after the consumption of pancakes that had been enriched with resistant starch (RS4) is a direct consequence of the increased short chain fatty acid production in the colon.

There is yet an important "on the other hand" we must not forget

GLP-1 is also partly responsible for the profound weight loss after bariatric surgery. In this case it is yet not the rise in short chain fatty acids, but as the scientists speculate the mechanical stretch and the influx of dietary fat that would otherwise have been absorbed earlier during the digestive process that triggers the release of the "satiety hormone" glucacgon-like peptide 1 (GLP-1, read more)
In fact, the aformentioned beneficial effects on the fatty acid metabolism and the concomitant reductions in insulin, which were brought about by an increase in GLP-1 (learn more about the potent fat burning effect of GLP-1) and decreases in GIP, respectively, have recently been traced back directly to the influence of SCFA in the long intestine. In a cleverly designed study, Lin et al. were able to show that the expression of these quasi-hormonal peptides, appears to be mediated by a direct interaction of bacteria-generated (or simply ingested) short-chain fatty acids in the gut with a speficic free free fatty acid receptor 3 (FFAR-3) in the gut lining (Lin. 2012).

As far as this part of the equation goes, we do therefore actually "know" something, what we do not know, but there are obviously a couple of my beloved "on the other hands" we still have to take into account. The most significant of these is unquestionably that impressive results as those that were observed in the very short run in the Shimotoyodome study will only arise in scenarios, in which the regular sugars and starches 90% of the Western population literally lives on are replaced with fermentable alternatives.

As long as you keep on the twinkies and dingdongs diet, the composition of your gut microbiome won't save you - no matter how good the critters are in turning fermentable starches into short chain fatty acids.
Figure 3: Different resistant starch content of various foods (% dry matter; based on Goni. 1996)
After all none of the simple sugars and easily digestible starches will even make it to the colon before they are either directly or after being disassembled by the enzymes in your gut taken up into the blood stream - the couple of  SFCA you either ingest as a supplement or your gut bacteria may be producing from additional pre-biotics (the term used in a very broad sense here and in the following paragraphs) you may be taking won't save you from the "fat" consequences.

Remember: If A → B & A → C, this does not imply B → C

Epidemiological studies such as Layden et al.'s 2012 analysis of the body composition of young, obese women in which the researchers found a negative correlation between body fatness (esp. visceral obesity) and the SCFA production in the colon do therefore not necessarily tell us that having a certain gut microbiome protects you from obesity (Layden. 2012). Observational studies like these, but also all experiments in which the human or rodent "participants" had the chance to compensate for the intake of fermentable starches or other supplements by skipping on foods they'd otherwise consume, simply tell us that eating fermentable starches is better than eating sugary junk - not more, but also not less.

Can saturated fat cause endotexemia? Learn the answer here!
If the ladies with the lower visceral fat in the Layden study consumed a diet that was devoid of fermentable starches, they would not produce any short chain fatty acids no matter how the composition of their gut microbiome may look like (in fact it would soon look like a "ghetto" full of unwanted bacterial tenants not paying their rent in form of healthy SCFA ;-). It should be obvious that the same goes for the anti-cancer effects of the SCFAs butyrate, propionate and acetate (Matthews. 2012), as well as all the other beneficial health effects which have been linked back to the bacterially manufacture two- to six-carbon chain FAs.

All the aforementioned benefits require the reguar ingestion of more than just trace amounts of fermentable starches. These pre-biotics will automatically have the "beneficial" bacteria in your gut get the better of the "bad guys" and it is a necessary prerequisite that any probiotics you are consuming either in pill form or from enriched foodstuff can take full effect. In other words:

Pre-biotics don't support probiotics, it's the other way around. Probiotics can support and accelerate the desired permanent change the regular consumption of prebiotics will bring about.

I know the product descriptions on the shiny websites of the snake oil industry will conceal that, but without a consequent and permanent change in your dietary habits, you can as well flush your super-potent 100 billion bacteria per serving probiotic directly down your toilette.



Even the nicest subtenants can become a real problem, when they come over without being asked day by day. Unfortunately, all sorts of gut bacteria (even the "good" ones) have as imilarly nasty habit of translocating through a leaky gut wall into parts of your body, where you certainly don't wont them... read about the nasty consequences, here
Long story short: All the current hoopla about probiotics, the tons of "enriched" products on the shelves of the supermarket, the capped super-*place your favorite strain here* with bazillions of "life-bacteria" in them and for which you would have to spend half your monthly salary, if you wanted to consume enough of them to override the baseline effect your diet, all of them are about as useful as a stimulant based fat burner on a hypercaloric diet.

You are what you eat, not what your supplement! The same goes for the composition of the bugs in your gut and if you want them to produce short chain fatty acids for you you better make sure they get the raw materials on a consistent basis. That this works like a charm within no more than 6 days is evidenced by the study publication of which triggered this lengthy discussion.

Whether all the purported health benefits will become visible in the short, long or very long term will yet still have to be elucidated... and that this is probably not going to happen, when you try to get your fermentable starches from bread only (0.25g per slice vs. navy beans 10g per 1/2 cup and even bananas 5g per banana)

References:
  • Goñi I, García-Diz L, Mañas E, Saura-Calixto F. Analysis of resistant starch: a method for foods and food products  Food Chemistry. 1996; 56(4):445–449.
  • Layden BT, Yalamanchi SK, Wolever TM, Dunaif A, Lowe WL Jr. Negative association of acetate with visceral adipose tissue and insulin levels. Diabetes Metab Syndr Obes. 2012;5:49-55. 
  • Klosterbuer AS, Hullar AJH, Li F, Traylor E, Lampe JW, Thomas W, Slavin JL. Gastrointestinal effects of resistant starch, soluble maize fibre and pullulan in healthy adults. British Journal of Nutrition. 2013 [Epub ahead of print].
  • Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240.
  • Shimotoyodome A, Suzuki J, Kameo Y, Hase T. Dietary supplementation with hydroxypropyl-distarch phosphate from waxy maize starch increases resting energy expenditure by lowering the postprandial glucose-dependent insulinotropic polypeptide response in human subjects. Br J Nutr. 2011 Jul;106(1):96-104.
  • Wroblewska M, Brzuzan L, Jaroslawska J, Zdunczyk Z. Effect of buckwheat sprouts and groats on the antioxidant potential of blood and caecal parameters in rats. Int J Vitam Nutr Res. 2011 Sep;81(5):286-94.

15 comments:

  1. Inulin is another option for a fermentable fibre that is present in two of the greatest tasting vegetables in existance, garlic and onions.

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  2. I'm not sure that the effects of a high fiber diet are as clear-cut as you make out in this article. For instance, a diet containing 30+ grams of fiber, including resistant starch, has been consistently shown to reduce total and free testosterone levels (estrogen as well, however). From a personal perspective, inulin supplementation lowers my libido. What are your thoughts on this? Thx.

    Edward Clements
    www.muscle-health-fitness.com

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    Replies
    1. changes in hormone levels in the normal range have no effect on body composition and I wonder if you experienced the drop in libido before you knew about potential changes in hormone expression (or if they are simply to avoid farting during intercourse ;-)

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  3. Adel, this post is reading very good. Don't know what you have changed, but keep it up.

    What about "bad guys"? How they influenced by feeding RS?

    Also very interesting thing about hot/cold food resistant starch content difference. What is behind this?

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    1. hmm... I thought I had seen a reply by Primalkid here in the overview. Wonder where that has gone, I just hope I did not accidentally delete it with the tons of spam... if so, sorry Alex! That being said, that's like it is always in the "wilderness" those who are best adapted to the environment survive. So if you add those RS to the diet, this makes the "environment" more homily for the "good guys", they survive and simply push the bad guys away.

      Heat changes the make-up of the starch, it unfolds and is more susceptible to digestion; ripening (as in Bananas, for example) does the same. A ripe banana has almost no starch

      Delete
    2. Oh my, here it is: I must really have deleted it... sorry "Kid" ;-) I will just quote your answer:

      Primalkid initially answered: "Maxim, I need Adel to confirm/dismiss this, but my understanding is that the "bad guys" compete with the "good guys" for nutrients and resources, so by supplying the "good guys" with the food they need to colonize, they crowd out the "bad guys" which improves the gut.

      With regard to heating, think of digestion. They are similar in that the RS gets broken down. Usually the starch turns into maltose, which is why a raw potato is starchy but once baked it is mushy and palatable."

      Delete
  4. Interesting post.

    The listing of raw legumes in the right hand column of Table 3 caught my eye. I sprout mung beans, and recently happened upon soaked mung beans as a snack or as an appetizer.

    I simply tasted them one morning, out of curiosity, after soaking them overnight, expecting them to taste bland or bitter, but the taste is similar to raw lima beans, which I loved when I was kid.

    I noticed they stimulate my appetite, in a good way. I come back and snack often enough that the sprouts don't have time to get very big.

    Here's the "recipe": 1/4 c. soaked overnight in an open glass canning jar. Pour off the excess water and enjoy! Rinse again in the evening and enjoy! Repeat until their gone.

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    1. thanks for the recipe... reminds me hat I shoul put this on the list of categories for the relaunch

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    2. Bacterial production of short-chain fatty acids in the gut is totally news to me, so this is really interesting.

      In the test-tube short-chain lipids form micelles, and do many of the same things detergents can do. They readily partition into long-chain lipid structures and coat or extract membrane proteins and lipids.

      I'm now curious to find out what other functions they may have, especially relating to lipid absorption and transport.

      Delete
  5. Great idea! Thanks for sharing Ramp Up Your Short-Chain Fatty Acid Production With Fermentable Starches Within 6 Days. Longterm Fat Loss, Gut Health & Cancer Protection Possible. Nice! Your curtains look beautiful, too! And loll at tutorial on removing black spray paint from garage floor. Awesome!!! I’m your newest follower from Creative Bloggers Hop. Please follow

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  6. I took long term antibiotics (2 yrs) and then Accutane for acne and my gut is a mess constant diarrhea, bloating, hemmroids, dry skin, rashes etc. Is a high starch diet the way to go? I dont seem to tolerate dairy and avoid grains besides maybe some white rice (rarely). I think eggs are also a bit of an issue. heck I might just about be allergic to everything. My joints ache, often after meals. adding a higher dose of Colostrum seems to help a bit so far but ive tried many things over the years with limited results. I'm toxic and aging at a rapid rate but coconut oil and colostrum seem to be the most helpful so far. Any tips would be great I'm a 21 year old male.

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    Replies
    1. I am not credible or anything, but you might want to check up on fecal transplants.

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    2. Thanks Maxim, I am certainly aware of them but have been holding it off as a last resort. I think I'd have to do the procedure myself and having never even done an enema I'm not so confident. Even finding a donor would be difficult as I'm not sure anyone I know would be aware of such a strange type of procedure.

      Delete
  7. GLP-1 raises insulin levels. Insulin blocks the oxidation of fats?
    Malonyl CoA?

    The metabolism doesn't go up without IGF-1 to IGF-1 R binding (triggering IRS-1). Pyruvate metabolism (odd chained fatty acids) results in hypoglycemia which is hyperinsulinemia which blocks fatty acid oxidation and triggers weight gain.

    The shortage of short chained amino acid dehydrogenase? Triggers hyperinsulinemia.

    Ask the starving kids in Ethiopia with the big bellies.


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  8. It is a helpful information. Hypotheses such as the "cholesterol is bad for your heart", the "pasta and rice will keep you lean.And we protect our body to prevent sickness.


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