Research Review: Say hello to (my trillions of) little friends

By Helen Kollias

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Lonely? Well you shouldn’t be, because you have trillions of friends with you all the time. Sure, they’re kind of small, but they’re always with you, wherever you go.

In fact, they’re such good friends that you have more of them than cells in your body! You have hundreds of trillions of micro-organisms in your body, while you have only a measly ten trillion cells. Most of those micro-organism buddies are bacteria.

You may think –- rightly so –- that “trillions” sounds like a lot. Luckily, all those bacteria only weigh about 2 kg, so just think of it like carrying around a well-loaded purse made up of little wiggly things. If you really want to lose 2 kg, just mentally subtract your bacteria since it really isn’t “you” anyway.

But where do all these bacteria live? Condos? Tents? Nope. They mostly live in the gut or intestines of your body, while about 10% of them live on your skin. The outer bacterial environment on the skin helps prevent the growth of other micro-organisms such as those that produce yeast and fungal infections. The inner bacterial environment – known as “gut flora” – has a similar function, but also does lots of other things. Collectively, gut flora have as much of a metabolic impact as any other organ in the body. They’ve even been christened the “forgotten organ” to underlie their importance.1

Bacteria functions

Aside from being a cool name for a band (“Dude, Gut Flora totally ROCKS!”), gut flora have three important functions: protective, structural, and metabolic.

ohara-am-shanahan-f-gut-flora-2006
Bacterial functions.

Protective function

Your intestinal bacteria protect you in various ways: via pathogen displacement, nutrient competition, and making anti-microbial factors.2 Your gut bacteria protect you from “bad” bacteria, viruses, fungi and other pathogens by not letting these pathogens get a foothold. Just like a rowdy gang, your gut bacteria crowd out other micro-organisms, take all the food and make biological weapons (anti-microbials) to keep the pathogens out and you healthy.

Structural function

Structural functions of your intestinal bacteria include barrier fortification, tightening of “tight” junctions, induction of immunoglobulin A and immune system development.

Barrier fortification means that the bacteria provide a physical barrier between your insides (blood vessels of the gut) and the outside (lumen of the gut). Wait a minute, you might say… my guts are on the inside! Well, technically, the lumen of your gut is “outside”. It may be hard for you to think of the inside of your intestines as being your outside, but it is -– in the simplest terms you are a tube with your gastro-intestinal (GI) tract running though you. So, your GI tract is a part of the outside world just like the centre of a toilet paper roll is not toilet paper. Stuff that you ingest must interact with the “inside outsides” of you (the cardboard layer of the toilet paper roll) before getting through to the “inside insides” of you (the inner paper layers).

Another structural protective function of the bacteria is to make the space between the cells of the gut even smaller (aka tightening junctions). While cells of the gut are already very close to one another (aka tight junctions) the closer they are to each other the fewer unwanted things pass through. The “cardboard toilet paper roll” (or the walls of your GI tract) isn’t solid, but rather slightly permeable, in order to let nutrients through. But these walls can’t be too easily passed; otherwise stuff that you don’t want in your bloodstream may leak through. If the junctions aren’t tight they become hyperpermeable or leaky. This is how you end up with leaky gut. Relatively looser spaces between gut lining cells allow large food particles past into your bloodstream. Leaky gut has been implicated in a wide range of disease including allergies, asthma, eczema, celiac disease, Crohn’s disease, irritable bowel diseases (IBD), other autoimmune diseases such as chronic fatigue syndrome or rheumatoid arthritis, and even autism.3

From Nature Molecular Biology, a diagram of junctions between intestinal cells. The microvilli line the intestines.
From Nature Molecular Biology, a diagram of junctions between intestinal cells. The microvilli line the intestines.

Induction of immunoglobulin A (IgA) and immune system development by your gut bacteria are inter-related. IgA is a protein (specifically an antibody) that binds to foreign or bad things like antigens (foreign proteins), food, bacteria and viruses so that these “bad” things aren’t absorbed into the gut cells. The cool thing is that IgA is relatively non-inflammatory compared to other immunoglobulins G and M (IgG and IgM.) As bacteria enter your gut in the first few months after birth, it triggers IgA to be secreted into your gut.

Research question

Gut flora also help with digestion, absorption, and metabolism of what you eat. This includes helping with the breakdown of non-digestible foods (or parts of foods), metabolizing carcinogens, making vitamins (biotin and folate) and absorbing ions (magnesium, calcium and iron). The most well known function of your gut bacteria is the breakdown of non-digestible or partially digestible foods, such as beans, by the process of fermentation that leads to socially awkward situations, especially if a dog is not nearby to blame.

This is where things get interesting. The bacteria you have can and do affect your metabolism. If you happen to have bacteria that can digest more polysaccharides, then they will increase your polysaccharide metabolism so that you can absorb previously indigestible polysccharides, which potentially leads to increased bodyweight.4

The article I’m reviewing this week is hot off the press –- actually it hasn’t been published on paper yet, just online –- and it compares blood metabolites in mice without any bacteria (germ free) and “conventional” mice with an average amount of gut bacteria.

Wikoff WR, Anfora AT, Liu J, Lesley SA, Peters EC & Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proceedings of the National Academy of Sciences 2009. Early edition: 1-6.

Methods

The methods are pretty straightforward: Researchers compared blood serum of conventional or normal mice compared to blood serum of mice without gut bacteria (germ free – GF). Using high performance liquid chromatography (HPLC) and mass spectrometry (MS) they identified biochemicals (or metabolites) in the serum of the mice. Now, I know you aren’t a mouse –- unless you’re Brain from “Pinky and the Brain.” But it is really hard to find people without any gut bacteria that are willing to eat exactly the same thing and it’s even harder to find a group of people that are nearly genetically the same –- so we’re stuck with mice.

Results

The researchers found 3,975 biochemicals that were the same in both groups. So bacteria didn’t have an effect on those.

The conventional group had 145 additional biochemicals and the bacteria-free had 52 different biochemicals.

Of the 197 different biochemicals only 19 were significantly different (statistically speaking). Some of the more interesting ones are:

  • Tryptophan: Germ free mice had 1.7 times less tryptophan than conventional mice
  • Serotonin: Conventional mice had 2.8 times more serotonin than germ free mice
  • Equol sulphate: This is a compound only found in conventional mice and it has been linked to decreased rates of prostate cancer5
  • A number of glycine conjugates (products of chemical reactions), phenylpropionylglycine and phenylacetylglycine, were found only in conventional mice, and in amounts 3.8 times higher, respectively.

Conclusion

In recent years, people have been paying more attention to the health of their gut and what organisms are living in there. Food makers have produced things like yogurts with live culture bacteria and begun to market more foods as “prebiotic/probiotic”. (Although buyer beware: recently, one of the PN team stumbled across yogurt marketed as “healthy” and “wholesome” that included candy bits such as Oreos and tiny M&Ms.)

Give credit for this revolution to Barry Marshall, who discovered the cause for stomach ulcers and gastritis was a bacterium (Helicobacter pylori) in 1984.6 Taking one for the science team, he infected himself with the bacteria -– by drinking a beaker of H. pylori -– and gave himself gastritis in order to prove the bacteria caused the disease. Even then it was ten years before antibiotics became the standard treatment for ulcers and gastritis.

While disease and health have been linked to gut bacteria this study goes a step further and looks at the effect of those bacteria on your metabolism. In 1984, it seemed farfetched for bacteria to cause ulcers. Today it may seem farfetched that bacteria could change your metabolism.

Hopefully in the future we will be able to pinpoint which bacteria are responsible for what metabolites and prescribe specific bacterial cultures, but until then make sure that you keep your gut bacteria happy by using probiotics and live culture yogurts, especially during and after rounds of antibiotics and anti-inflammatories. Oh, and if you’re stressed it wouldn’t hurt to hedge your bets and keep restocking your body with “good” bacteria – there was a reason ulcers flared up when people were stressed.

Until next time, adios, amoebas.

bacteria-cowgirl

References

Click here to view the information sources referenced in this article.

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