Get to know those little buggers in your (aging) gut

The next time you poop, take a moment to realize that you have become more human by doing so. Sure, you have gotten rid of some smelly ‘uncivilized’ stuff, but at the same time, a large amount of little buggers have vacated your gut. Since these little buggers live in and on our bodies in about a 1:1 ratio with our own cells1, simply by pooping some out, you have tipped the scale to being slightly more ‘human’. Those little buggers are bacteria, and constitute what scientists call the ‘microbiome’. It’s a thing that (some) scientists love to dig in to, sequencing your poop to find out what types of bacteria live there. These bacteria are involved in the breakdown of food and the production of vitamins, so their impact can be vast. There seem to be good guys and bad guys, but how important is it all?

Gut microbiome and the media

And that is the typical cycle that the media goes through regarding the gut microbiome.

So what can we really say about it?

This much is true: changes in the gut microbiome’s composition correlate with a lot of things, astonishingly so. This includes; obesity2, irritable bowel syndrome (IBS)3, colon cancer4, cardiovascular disease (CVD)5, inflammation6, frailty7, your diet8, and our favorite; aging9–13. And more correlations keep popping up.

That’s why the media has a field day about it. But what we are left with is the typical problem of not really being able to tell the difference between correlation and causation. But correlation is definitely there, and causation feels temptingly close, so an overview model with arrows pointing in every direction might look like this:

Microbiome aging diagram

What’s the relation to aging?

It is undeniable that the microbiome changes with age. Of the two major groups (phyla) of little buggers in your gut, Bacteroidetes and Firmicutes9it has been shown that a skewing occurs towards having more Bacteroidetes with age10. What’s more, it is also shown that having more of that group is correlated to having more frailty and impaired function with age6. We know that the microbiome correlates with the food we eat8, and indeed, healthy aging individuals (i.e. less frailty, more Firmicutes) seem to eat foods with more fiber and less fat content than their unhealthier aged peers6. Here is a drawing summarizing the literature6,10–12:

Microbiome aging diagram 2

What’s more, interventions in mice that extend lifespan, such as dietary restriction14, and feeding the drug Rapamycin15 (one of the most promising interventions to delay aging), also impact the gut microbiome. So the picture is getting pretty clear, the microbiome is heavily implicated in aging, healthy aging, and longevity. So let’s use it to take back lost youth! So are the Bacteroidetes the bad guys?

Here is why it’s more complicated.

Those are all correlations. It’s not clear if aging causes our microbiota to change as described, or vice versa. Furthermore, when thinking about how to use these little buggers as therapies, one thing to keep in mind is that the composition of bacteria changes throughout the length of the gut. Most research is just based on sequencing the end product, poop, which is thought to mainly reflect the composition of bacteria in one section (the distal colon)12. This makes it hard to say what the ‘best’ bacteria might be for us (it could be different throughout the gut). On top of that, there are thought to be over 600 genera of bacteria existing in the gut16, with at least 1000 – 1200 species possible, and any individual may be having at least 160 of these17. Remember, the way scientists categorize a species is with the following hierarchy: kingdom, phylum, class, order, family, genus, species. So the Bacteroidetes ‘phylum’ actually includes a lot of different species. So while the above aging research painted a picture of Bacteroidetes as being bad, this phylum has been shown to be actually less present in obese mice18, and obese humans2,19 though even these findings can’t always be replicated, illustrating the fact that scientists are still at the start of figuring out how our microbiome influences everything. The science is simply at a very early stage of understanding for how to actually use bacteria to influence our health in aging.

The bottom line: What can you actually do about it to benefit your health?

Your microbiome is related to chronic inflammation and health complications, and those are related to aging. So let’s try to keep it in check. Here’s what I would recommend doing:

  • Fiber. Eat it. It’s the recurring theme, linking health to the microbiome. So eat foods with fiber (i.e. broccoli, carrots, cabbage, celery, courgette, eggplant, kale, pumpkins, turnips… those will do the trick, but the list goes on).
  • Yoghurt… why not eat it? Or something else with live bacteria, such as kefir or cultured vegetables (i.e. sauerkraut or kimchi).

That’s it for now.

Ok. I’m sorry to have disappointed you, you have read through this whole blog just to have been left with a simple recommendation, to eat fiber, and a not-so-affirmative recommendation to eat yoghurt, where the yoghurt part was already suggested over 100 years ago by nobel prize winner Élie Metchnikoff20. But that’s where we stand with things. If you want some more entertainment around the microbiota hype though, you might want to read about the rises and crashes of microbiome based therapeutics companies, or a story on how a scientist has injected himself with the stool of a hunter-gatherer. You might also be interested in seeing perhaps the most promising direction for microbiome research: personalized nutrition21.

In any case, go eat that fiber.


Going deeper…

1.
Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. Cold Spring Harbor Laboratory Press; 2016. doi: 10.1101/036103
2.
Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature. 2008;457(7228):480-484. doi: 10.1038/nature07540
3.
Jeffery IB, O’Toole PW, Öhman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut. 2011;61(7):997-1006. doi: 10.1136/gutjnl-2011-301501
4.
Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Research. 2011;22(2):292-298. doi: 10.1101/gr.126573.111
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Tang WHW, Wang Z, Levison BS, et al. Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk. New England Journal of Medicine. 2013;368(17):1575-1584. doi: 10.1056/nejmoa1109400
6.
Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. May 2016. doi: 10.1038/nature11319
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Jackson MA, Jeffery IB, Beaumont M, et al. Signatures of early frailty in the gut microbiota. Genome Medicine. 2016;8(1). doi: 10.1186/s13073-016-0262-7
8.
Jumpertz R, Le DS, Turnbaugh PJ, et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. American Journal of Clinical Nutrition. 2011;94(1):58-65. doi: 10.3945/ajcn.110.010132
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Eckburg PB. Diversity of the Human Intestinal Microbial Flora. Science. 2005;308(5728):1635-1638. doi: 10.1126/science.1110591
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Claesson MJ, Cusack S, O’Sullivan O, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proceedings of the National Academy of Sciences. 2010;108(Supplement_1):4586-4591. doi: 10.1073/pnas.1000097107
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Zapata HJ, Quagliarello VJ. The Microbiota and Microbiome in Aging: Potential Implications in Health and Age-Related Diseases. Journal of the American Geriatrics Society. 2015;63(4):776-781. doi: 10.1111/jgs.13310
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Jeffery I, O’Toole P. Diet-Microbiota Interactions and Their Implications for Healthy Living. Nutrients. 2013;5(1):234-252. doi: 10.3390/nu5010234
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Kong F, Hua Y, Zeng B, Ning R, Li Y, Zhao J. Gut microbiota signatures of longevity. Current Biology. 2016;26(18):R832-R833. doi: 10.1016/j.cub.2016.08.015
14.
Zhang C, Li S, Yang L, et al. Structural modulation of gut microbiota in life-long calorie-restricted mice. Nature Communications. 2013;4. doi: 10.1038/ncomms3163
15.
Bitto A, Ito TK, Pineda VV, et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. eLife. 2016;5. doi: 10.7554/elife.16351
16.
Zhernakova A, Kurilshikov A, Bonder MJ, et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 2016;352(6285):565-569. doi: 10.1126/science.aad3369
17.
Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. doi: 10.1038/nature08821
18.
Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences. 2005;102(31):11070-11075. doi: 10.1073/pnas.0504978102
19.
Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: Human gut microbes associated with obesity. Nature. 2006;444(7122):1022-1023. doi: 10.1038/4441022a
20.
Brown A, Valiere A. Probiotics and medical nutrition therapy. Nutr Clin Care. 2004;7(2):56-68. [PubMed]
21.
Zeevi D, Korem T, Zmora N, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163(5):1079-1094. doi: 10.1016/j.cell.2015.11.001
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