Thursday, August 14, 2014

They Dictate What You Like, They Dictate What You Crave and They May Even Determine Whether You're Lean or Fat: The Bacteria in the Gut - The Latest Evidence Reviewed

The alien inside - billions of bacteria in your gut interact with your central nervous system and take command over your metabolism and - probably - even about what you want to put into your mouth.
Wouldn't it be great if it was not your lack of willpower and your unhealthy food choices that were to blame for the potbelly you're carrying around? Wouldn't it be awesome if you could blame your misery on someone else? And wouldn't it be best if that someone was a dirty little microbe in your gut? Someone who cannot fight back, when you chose him as a scapegoat? That would be great, right?

Well, in today's SuppVersity Article we're going to take a look at a bunch of studies and hypothesis that may actually allow you to find a new excuse for your inability to lose weight. But beware! While I wouldn't say that researchers who favor the "evolutionary conflict between host and microbes" theory as an alternative explanation for the ever-increasing obesity rates are totally off. What I will say, however, is that this is at best a contributing, maybe even just a corollary factor in the etiology of the obesity epidemic.
You can learn more about the gut & your health at the SuppVersity

Fiber for Female Fat Loss

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

The Macrobiotic MaPi2.0 Diet
We know for quite some time that individual members of the microbiota, and consortia of those microbes are highly dependent on the nutrient composition of the diet.
  • Prevotella grows best on carbohydrates; dietary fiber provides a competitive advantage to Bifidobacteria (González‐Rodríguez. 2013)
  • Bacteroidetes has a substrate preference for certain fats (Wu. 2011)
Scientists have also found some specialist microbes, e.g. mucin degrading bacteria such  as Akkermansia mucinophila. They thrive on secreted carbohydrates provided by host cells. Other butyrate producing microbes, e.g. Roseburiaspp., fare better when they are delivered polysaccharide growth substrates in the diet. Specialist microbes that digest seaweed have been isolated from humans in Japan (Hehemann. 2010). African children raised on sorghum have unique microbes that digest cellulose (De Filippo. 2010). Many other examples exist (Fava. 2012).
We have tons of associations, but little experimental evidence: All this does yet not mean that the specialized gut microbiome will also affect the dietary intake of the host. You could after all argue that you could get rid of Prevotella by simply cutting out all carbs from your diet, but scientists believe that the specialization works both ways.
There is circumstantial evidence for a connection between cravings and the composition of gut microbiota. Individuals who are “chocolate desiring” have different microbial metabolites in their urine than “chocolate indifferent” individuals, despite eating identical diets (Rezzi. 2007).
Figure 1: A study by Rezzi et al. showed that chocolate cravers have a different microbiome than their peers (Rezzi. 2007)
In spite of these intriguing results and a plethora of evidence for mood and central nervous system effects of certain bacteria in rodents, the definite evidence of a causal relationship between gut microbes A, B & C and certain food preferences, let alone "addictions" is still missing.

It's not as if there was no evidence, it's just not really compelling (yet?)

An area where the mechanisms appear to be more evident is the effect of certain bacteria on the expression of certain molecular receptors in the gut. Germ-free mice for example have altered taste receptors for fat on their tongues and in their intestine compared to mice with a normal microbiome (Duca. 2012). Since an increase in fat receptors is associated with an increased preference and intake for fatty foods and energy, an over-expression of these receptors could certainly be involved in the etiology of obesity.
Both, low dose penicillin at weaning (blue) and at birth (red) lead to significant obesity in male pups later in life (Cox. 2014).
Latest research says: Disruption of gut bacteria early in life can lead to obesity in adulthood! Certain microbes found in the gut may protect against obesity and diabetes. A study published by Cell Press August 14th in the journal Cell reveals that these microbes shape their hosts' metabolism very early in life and that disrupting them with short-term exposure to antibiotics during infancy can cause metabolic changes that appear to increase the risk of obesity in adulthood.

These findings in mice are helping researchers identify which gut bacteria are crucial to metabolic health. Such information could be used to help restore levels of those helpful microbes after an infant has received life-saving antibiotics, thus  promoting healthy metabolism in adulthood.
In conjunction with other scientific evidences, such as the increased intestinal expression of cannabinoid and opioid receptors in mouse and rat intestines in response to the oral supplementation of L. acidophilus NCFM in rats and similar effects in human epithelial cell culture (Rousseaux. 2006), the Duca study suggests that the composition of microbes in our guts could in fact actively alter our food preferences by modulating the receptor expression or transduction (Collins. 2012).

Is a "gut dysbiosis" the reason we are fat?

The idea that not having the "right" bacterial make-up could be at the heart of the obesity epidemic has recently received significant scientific attention. Backhed and colleagues showed that mice genetically predisposed to obesity remained lean when they were raised without microbiota (Bäckhed. 2004).
Figure 2: Germ-free mice stayed lean, in spite of the fact that they were genetically predisposed to become obese and irrespective of their increased food intake (Bäckhed. 2004). When they were inoculated with the microbiota from regular obese mice (CONV-D), however, they became just as obese as their conventional peers (CONV-R)
When the mice were "infected" with fecal pellets from a conventionally raised obese mice, they became obese again. That this could happen in humans as well is supported by data from Ridaura et al. (2013) who observed that the inoculation of germfree mice with microbiota from an obese human produced similar results.

Let's put everything together, now!

As you can see in the graphical illustration in Figure 3, the taste receptor interactions are not the only scientifically proven changes. There are also well-known endotoxin induced effects on mood and anxiety (Amaral. 2008; Chiu. 2013) of which Hill et al. have shown (albeit in a different context) that it will affect food cravings (Hill. 1991).
Beware! If the scientists are right, the same probiotics that are good for people on a mixed diet may be bad for those who consume a low carb or ketogenic diet. I would thus be very reluctant to make any form of one-size-fits it all supplement recommendation! If there is one take home message from what we already know, it's that, in the long run, unbalanced diets (low-to-no whatever) will obviously put you at greater risk of developing a highly specialized obesity-promoting gut microbiome.
Figure 3: Like microscopic puppetmasters, microbes may control the eating behavior of hosts through a number of potential mechanisms including microbial manipulation of reward pathways, production of toxins that alter mood (shown in pink, diffusing from a microbe), changes to receptors including taste receptors, and hijacking of neurotransmission via the vagus nerve (gray), which is the main neural axis between the gut and the brain (Alcock. 2014)
Now Alcock et al. who created this illustration speculate that the weight loss and inhibition of weight gain we've seen in trials using probiotic yogurts (Kadooka. 2010; Mozaffarian. 2011) could be mediated, at least in parts, by microbial interactions with the vagus nerve:
If microbial control is mediated through the vagus nerve, then microbial signals should interfere to some extent with the physiological regulation coordinated by the vagus nerve. [...] We predict that people experiencing cravings should have lower vagal tone. Furthermore, it is possible to block or sever the vagus, which we predict would subdue microbial signaling via the vagus nerve, and thereby alter food preferences. This would be consistent with studies showing that blocking the vagus nerve can lead to weight loss." (Alcock. 2014)
In conjunction with the aforementioned effects and the influence of population size and composition on cravings and high fat, high carbohydrate preferences foods Alcock et al. believe to have enough evidence for the existence of what they call an "evolutionary conflict between the host and microbiota" which may lead to cravings and cognitive conflict with regard to food choice.
Will Engineered Super-Bacteria Help Even Gluttons to Stay Lean? Scientists "Produce" Anti-Obesity Bacteria to be Administered in the Water | more
Personally I don't consider the evidence convincing enough to assume that the suppression oo modification of microbial signals from the gut alone will fix what is currently deemed a problem of self-control and bad food choices | What's your take? Comment on Facebook!

I do not doubt though that "acquired tastes" may at least be reinforced by corresponding microbial selection in the gut. Resetting the microbial make-up and/or modifying it via pre- and probiotic foods and supplements is thus unquestionable an interesting, yet still not fully understood strategy to complement lifestyle intervention that focus on diet and exercise.

And let's not forget: Both diet and exercise have been shown to have a major impact on the gut microbiome, as well (Gotthardt. 2014; Hold. 2014)!
  • Alcock, Joe, Carlo C. Maley, and C. Aktipis. "Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms." BioEssays (2014).
  • Amaral, F. A., et al. "Commensal microbiota is fundamental for the development of inflammatory pain." Proceedings of the National Academy of Sciences 105.6 (2008): 2193-2197.
  • Bäckhed, Fredrik, et al. "The gut microbiota as an environmental factor that regulates fat storage." Proceedings of the National Academy of Sciences of the United States of America 101.44 (2004): 15718-15723. 
  • Chiu, Isaac M., et al. "Bacteria activate sensory neurons that modulate pain and inflammation." Nature (2013).
  • Collins, Stephen M., Michael Surette, and Premysl Bercik. "The interplay between the intestinal microbiota and the brain." Nature Reviews Microbiology 10.11 (2012): 735-742.
  • Cox et al. "Altering the Intestinal Microbiota during a Critical Developmental Window Has Lasting Metabolic Consequences." Cell 158 (2014):705–721.
  • De Filippo, Carlotta, et al. "Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa." Proceedings of the National Academy of Sciences 107.33 (2010): 14691-14696.
  • Duca, Frank A., et al. "Increased oral detection, but decreased intestinal signaling for fats in mice lacking gut microbiota." PloS one 7.6 (2012): e39748. 
  • Fava,Francesca, et al. "The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’population." International Journal of Obesity 37.2 (2012): 216-223.
  • González‐Rodríguez, Irene, et al. "Factors involved in the colonization and survival of bifidobacteria in the gastrointestinal tract." FEMS microbiology letters 340.1 (2013): 1-10.
  • Gotthardt, J. D., et al. "Exercise Promotes Enhanced Gut Microbial Diversity Compared to Sedentary Counterparts." International Journal of Exercise Science: Conference Proceedings. Vol. 9. No. 2. 2014. 
  • Hehemann, Jan-Hendrik, et al. "Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota." Nature 464.7290 (2010): 908-912.
  • Hill, Andrew J., Claire FL Weaver, and John E. Blundell. "Food craving, dietary restraint and mood." Appetite 17.3 (1991): 187-197. 
  • Hold, Georgina L. "The gut microbiota, dietary extremes and exercise." Gut (2014): gutjnl-2014.
  • Kadooka, Y., et al. "Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial." European Journal of Clinical Nutrition 64.6 (2010): 636-643.
  • Miras, Alexander D., and Carel W. le Roux. "Mechanisms underlying weight loss after bariatric surgery." Nature Reviews Gastroenterology and Hepatology 10.10 (2013): 575-584.
  • Mozaffarian, Dariush, et al. "Changes in diet and lifestyle and long-term weight gain in women and men." New England Journal of Medicine 364.25 (2011): 2392-2404.
  • Rezzi, Serge, et al. "Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals." Journal of proteome research 6.11 (2007): 4469-4477.
  • Ridaura, Vanessa K., et al. "Gut microbiota from twins discordant for obesity modulate metabolism in mice." Science 341.6150 (2013): 1241214.
  • Rousseaux, Christel, et al. "Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors." Nature medicine 13.1 (2006): 35-37. 
  • Wu, Gary D., et al. "Linking long-term dietary patterns with gut microbial enterotypes." Science 334.6052 (2011): 105-108.