Christmas food for thought: Feed me, all 100 trillion of me

The morning before Christmas eve, I’m sitting here in the dining room munching happily on the bits and pieces of what’s left of our gingerbread house that was only erected to its full glory the night before. I have not consumed this amount of carbohydrates in over a year.

Inside, a few species of my extensive gut microbe community are screaming bloody murder.

E. coli bacteria

FEEEEED ME!!!! Source: http://edbites.com/

When you eat, you’re not only feeding your own fleshy vessel, but also the 100 trillion of microbugs that thrive in your intestines. Hardly “along for the ride”, these bugs not only help us digest foodstuff, ferment carbohydrates and proteins but also heavily impact our metabolism and general health. Depending on their composition, they tweak our risk of cardiovascular diseases, Type II diabetes and may even cause obesity in humans. There’s tantalizing evidence that their reach extends to the brain, influencing mood, anxiety and cognition in mice.

However, the gut microbiota* is a fluid, ever-changing beast. In one previous study, researchers transplanted gut-free mice with fresh or frozen human poop to inoculate them with a microbiome of known composition. When researchers switched these mice’s plant-based diet to a high-fat, high-sugar one, the structure of the established microbiome changed within a single day: some species dwindled in number, while others exploded onto the intestinal stage, bringing with them their particular metabolic tricks. (*The word “microbiome” refers to the set of genes in the gut bugs).

Similar diet-induced changes have been found in humans. When babies are weaned from their mothers’ milk and switch to solid food, their gut bug community simultaneously go through tumultuous changes. The gut bugs of African hunter-gatherers vastly differ from those in people grown on a Western diet. But these changes take weeks, even lifetimes. Just how fast can the microbiome adapt and change to a new diet?

In a new study, researchers recruited ten volunteers and put them on two drastically different extreme diets for 5 days – as you can see below, the plant-based diet was rich in grains, fruits and vegetables (high-carb and high-fibre), while the animal-based diet consisted of meats, eggs and cheeses (high-fat, high-protein and low/no-fibre). Each day, the volunteers handed in a poop sample for the researchers to monitor.

Screen Shot 2013-12-23 at 10.24.18 AM

In general, the animal-based diet had a greater impact on gut flora than the plant-based one. It significantly increased the diversity of gut flora, enriching 22 species whilst decreasing the fibre-intake associated Prevotella in a life-long vegetarian on this meaty diet. The plant-based diet, on the other hand, only increased the abundance of 3 species, mostly those associated with carbohydrate fermentation.

Many of the changes made sense. An animal-based diet enriched putrefactive microbes, shifting carbohydrate fermentation into amino acid digestion, thus helping the body break down the onslaught of heaps animal protein. Several strains of immigrant bacteria – particularly those used for cheese- and sausage-making –settled down and made themselves comfortable in the native gut flora community. The meat-heavy diet also triggered microbes to activate pathways that degrade cancer-causing compounds found in charred meats, and enhanced the synthesis of vitamins.

On the other hand, several strains of potentially health-negative bacteria also multiplied in the meat-eaters. On a high-fat diet, we excrete more bile – a bitter fluid that may ruin a good fish dish – to deal with the digestion of fat. Bile is toxic to many gutbugs, but not to the mighty Bilophila (“bile-loving”) wadsworthia – a bile-resistant bacterium stimulated by saturated fats in milk that may cause intestinal inflammation, at least in mice. The high-fat content in the animal-based diet also triggered increased levels of microbe-produced DCA, which is previously linked to liver cancer in mice. However, as of now there’s no evidence that these risks also apply to people, and researchers caution against making health-related judgments (although some can’t resist the temptation).

On the whole, plant- and animal-based diets induced changes in host microbiome gene structure that resembled those of herbivorous and carnivorous mammals within a few days. Furthermore, the volunteer’s microbiome reversed back to their previous composition only 2 days after the end of the experiment. Researchers believe we might be looking at a fast-forwarded movie of millions of years of co-evolution between humans and their microbugs: when animal food sources fell scarce, our ancestors were forced to switch to a plant-heavy diet; a flexible gut-bug community could quickly and appropriately shift their repertoire and function to help digestion, thus increasing the flexibility of human diets and chances of survival.

Thus, when you gobble down the vast selection of Christmas dishes this year, remember to thank the flexibility of your gut flora for your diverse digestive powers. And remember that we can’t say one diet is better than the other for our microbiota; the take-home message is that they are incredible flexible, more so than we previously thought. In the end, it still comes down to the age-old wisdom: you are what you eat.

ResearchBlogging.org
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, & Turnbaugh PJ (2013). Diet rapidly and reproducibly alters the human gut microbiome. Nature PMID: 24336217

The skinny on gutbug-transplanted obesity

For centuries, mankind has looked into the vast skies and wondered “are we alone?” We still don’t know. But if we turn our gaze inwards, towards our own bodies, then the answer is a definitive “NO!”

SU10_gut-flora_opener_a_h

It’s a jungle in there. Source: http://protomag.com/

100 trillion microbugs thrive in our intestines, forming complex communities – called “microbiota”- that live with us in symbiosis. (The word “microbiome” that you often hear describes the set of GENES that a particular microbiota has). Our gut bugs munch on the foodstuffs that we inadvertently share with them, not only helping us digest carbohydrates and ferment fibre, but also heavily influencing our metabolism. In fact, depending on the composition of your microbiota, they may influence your risk of Type II diabetes, cardiovascular disease, and mood.

They may even help shape your waistline.

Numerous studies have shown that obese and lean people harbour divergent populations of gut microbes; when obese people lose weight on either a fat- or carbohydrate-restricted diet, their gut bug populations gradually shift to that of a lean person’s. A recent study surveying 292 Danes found that obese people have fewer and less diverse gut bacteria populations, constituting an impoverished state that correlated with increased inflammation and risk of future weight gain.

But these observational studies cannot tell us which came first: obesity or obesity-associated microbiota? In other words, can gut microbes CAUSE obesity?

Ridaura VK et al (2013). Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science doi:10.1126/science.1241214.

Researchers recruited four pairs of female human twins whom drastically differed in body composition (BMI difference >=5.5) and collected a sample of their microbiota. If you’re imagining long cartoonish needles, think again: since microbes heavily populate the large intestine, many hitch a hike with foodstuff and eventually gets shuffled out as poop – ready for collection. Researchers then transplanted the fecal samples into lean germ-free mice, fed them a standard low-fat diet and waited for the bugs to colonize the mice’s virgin guts.

Screen Shot 2013-09-12 at 9.20.24 PM

15 days later, the bodies of recipient mice morphed into their human donor’s composition and shape. As you can see above, while “lean” bug-receiving mice (left) retained their body fat levels, those getting “obese” bugs dramatically packed on the squishy pounds (right). When researchers inoculated a new group of mice with “pure” bacteria cultured from the original fecal samples, the same divergence in body fat gain was observed.

Screen Shot 2013-09-12 at 9.00.07 PM

Here’s a nifty summary. Source: Science 341 (6150): 1069-1070

The few extra pounds weren’t the big problem – mice receiving “obese” bugs also started metabolizing amino acids in a way often seen in insulin-resistant humans, suggesting that their metabolisms were becoming compromised.

The researchers next wondered if these negative changes in body composition could be prevented with a healthy dose of “lean” bugs in an epic “battle of the microbes”. Following “obese” germ-transplants, researchers fed the mice with standard low-fat chow and waited until the bugs stabilized in their guts. Before recipient mice showed apparent signs of weight gain, researchers dropped “lean” bug-inoculated mice into their home cages. Since mice regularly ate each other’s feces, housing the two together should hypothetically result in a hearty mingling of each other’s gut bugs.

Or so it seemed. Although the microbiota of “obese”-germ mice was infiltrated with that of “lean”-germ mice, the swap was a one-way street – “lean”-germ mice retained their original microbiota, as well as their svelte physique (red bar in the graph below). Co-housing saved “obese”-germ mice from their rotund fate; their fat gain dramatically slowed (Ob-ch, empty blue bar), as compared when housed alone (Ob-Ob, solid blue bar).

Screen Shot 2013-09-12 at 9.28.16 PMWhy this one-directional infiltration? Careful genomic analysis revealed the answer may be population diversity: because an obese germ community is less diverse than a lean one, it leaves many empty “niches” in the intestines – prime real estate for “lean” bacteria to move in. The fiercest invaders were from the Bacteroidetes family, whose overrepresentation in gut flora has previously been associated with leanness in mice.

If “lean” microbes tend to wipe out and replace “obese” ones, why is it that we have an obesity problem instead of a “lean” epidemic (I wish!)? The answer may partially lie in – you’ve probably guessed it – diet.  In the above experiments, all mice were fed the same low-fat high-fibre diet, regardless of the type of microbiota received. To see if diet changes anything, the authors cooked up two human diet based recipes, one high in fruits and vegetables but low in saturated fat, and one with the opposite composition.

Screen Shot 2013-09-12 at 9.31.26 PMScreen Shot 2013-09-12 at 9.31.39 PM

As you can see in the above left graph, when “obese”-germ mice gobbled the low-fat high-veg chow, they still gained more weight (Ob-Ob, solid blue bar) and showed signs of mild glucose intolerance, which was once again canceled by co-housing with their “lean”-germ peers (Ob-ch, empty blue bar. Compare it to the solid blue bar, see how there’s a trend towards decrease?) . However, on a diet high in fat but low in veg (right graph), “obese”-germ mice rapidly gained fat mass, regardless of whom they were housed with. In other words, a high fat diet barricaded any attempts that the “lean” germs might have made to invade the “obese” germ community (compare the solid and empty blue bars again).

Why is this the case? Bacteroidetes, the most successful invaders, are experts at breaking down dietary fibres into short-chain fatty acids, which can be used by the host as energy. Previous studies have shown – somewhat paradoxically – that these fatty acids promote leanness by inhibiting fat accumulation, increasing metabolism and enhancing the level of hormones that promote feelings of fullness. On a high-fat low-veg diet, the Bacteroidetes lacked the magic ingredient to work with and couldn’t establish themselves in the “obese”-germ mice. Any weight management benefits died off with the bacteria. The difference between high- and low-fat diet was only 11% by weight; it’s interesting to note that increasing fibre (as opposed to decreasing fat) may be more helpful in sculpting your waistline. I’d love to know what would’ve happened if the mice were fed a high-fat, high-fibre diet; would weight gain still be prevented by “lean” microbe transfer?

Screen Shot 2013-09-12 at 9.00.29 PM

Summary #2. Source: Science 341 (6150): 1069-1070

So how relevant are the findings for us humans? Results from studies looking at Bacteroidetes in humans have been mixed – they seem to increase in obese individuals in some studies. So the jury’s still out there. What I’m wondering is whether transplanting “obese” microbiota into ALREADY obese mice can REVERSE their weight gain. If so, it’s certainly possible to isolate a few important “lean” strains and develop them into probiotics with anti-obesity powers. That is, if you watch your diet.

In the meantime, I’ll still stick to the good old mantra: eat less, move more.

ResearchBlogging.org
Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, & Gordon JI (2013). Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 341 (6150) PMID: 24009397

Note: I just realized wordpress has been putting ads in some of the posts sporadically – my apologies if you were assaulted. It’s been taken care of!