February 22, 2012 | 2
In the last post I talked about babies eating poo how babies develop a gut flora. In this post I wanted to look at how that flora matures into adulthood.
As a baby grows it interacts with its environment and after about a year an infant’s flora will resemble their parent’s. This becomes particularly important as the baby starts to eat solid foods and no longer survives on a milk diet. Now any and all bacteria can have a shot at colonising. So what shapes the bacterial population from this point onwards? Tolerance dictates this uneasy state of play.
Given the colon of humans contains trillions of bacteria humans can really be thought of as ‘super-organisms’ as without the bacteria we would get very sick and without us the bacteria would die. We have co-evolved together to a point where we depend on the genes in the bacteria to perform functions that we cannot and in doing so we provide nutrients and shelter.
Despite the ‘all members live happily ever after’ picture that is commonly portrayed the immune system actually acts like the grumpy police chief in a cop movie waiting for the bacteria to make one wrong move then they’re out on their arses!
The problem, which I have mentioned in the last post, is how do we tell ‘good’ from ‘bad’ bacteria, or more specifically, since we can’t do without the ‘good’ bacteria but can’t afford to suffer the ‘bad’ how should the immune system respond to the presence of any bacteria? The only option is to be flexible.
The gut epithelium is a formidable barrier preventing access to the body. As well as mucus that is constantly being flushed through the system, taking everything with it, the epithelial layer can also be induced to express anti-microbial products and immune system signals. The B cells in the gut even produce antibodies capable of being secreted into the lumen called IgA’s (Immunoglobulin type A). These defences are enough to control bacterial numbers in the gut but recent research is showing that some members of the microbiome can repress the antimicrobial nature of the gut enough to allow their own survival, as long as they don’t poke the bear cause inflammation.
One of the ways our ‘good’ bacteria persist is to live in the mucous instead of on the actual epithelial cells. From the ‘good’ bacteria’s point of view it has access to the lumen where it’s (and our) food is travelling and by staying away from the cell surface they do not promote an inflammatory response.
But avoiding the surface isn’t always possible and inevitably good bacteria will interact with the surface through molecules known as Toll-like receptors (TLR). These TLR’s recognise patterns in molecules and are key in generating inflammatory responses. Obviously bacteria do not belong to the host so the activation of a TLR is bad news for a ‘good’ bacterium.
It has been shown that tolerance plays a major role at this point as the major ‘pattern’ the TLR’s recognise is a bacterial surface sugar called lipopolysaccharide (LPS). Over-exposure to LPS seems to result in desensitisation of the TLRs resulting in a decreased response over time. Some ‘good’ bacteria can even secrete molecules that inhibit an active TLR. This tolerance establishes an uneasy stand-off between the bacteria and the host. The bacteria that promote tolerance and prevent inflammation are often referred to as the ‘peace-keepers’.
The next group of commensal bacteria I like to think off as the ‘irritators’, and their role, and apparently the role of my sisters growing up, is to irritate and push me/the immune system. In the end this irritation is a good thing as the immune system is forced to develop to handle these irritating species. A good example of an irritator is the segmented filamentous bacteria (SFB). It has been shown they can’t be cultured in the lab, nor will they grow happily on their own in an otherwise sterile animal gut but specialise in surviving in a microbe rich yet pathogen free environment.
These bacteria are super important but so little is actually known about them. What we do know is that without them the body struggles to develop the correct immune cell populations in the gut and even anatomical structures such as the Peyer’s Patches develop abnormally.
These irritators are not capable of much more than being irritating and forcing the immune system to notice them but in doing they strengthen the gut’s defences. Only in immunocomprimised hosts can these guys do any harm and by that stage they are really the least of your problems.
The last member of the commensals is the pathobionts. The pathobionts are trying to cause disease but their efforts, in a perfectly balanced system, actually keep you healthy. The great example here is Helicobacter pylori. This bacterium persists by modulating the host’s immune system and down regulating any activity against it but also by altering the local physiology. This bacterium increases gut pH around itself while also down regulating gut mucous production as part of its normal lifecycle. If the host is making to much acid or mucous then significant disease and eventual break down of the epithelial barrier can occur resulting, notably, in colonic cancers but the bacteria keeps this in check by accident. Cases of ulceration due to H. pylori are thought to be caused only by particularly aggressive strains or inappropriate responses by the host.
At the top of this post I said I wanted to describe the changes that happen between baby and adult but that process is too difficult for me to do here. The changes in the species and the populations of each species are fluid and depend on all the ways you interact with your environment. Vegans have different microbiomes to vegetarians and omnivores. Antibiotics will alter your microbiome but so will a long holiday. The point is that certain functions need to be performed by the bacteria in your gut, irrespective of the actual bacterial species that perform them. The only rule is don’t make the host sick and you can stay.
Perhaps then I should answer the question how does our body tell good from bad? In reality the body can only assume that all are bad, it’s the bacteria that tell the body whether they should be tolerated or destroyed. This becomes super important as it is, generally speaking, the ones we tolerate that we cannot do without.
In the next post I talk about what happens when this delicately balanced system shifts and how this might affect our health.
Fujimura KE, Slusher NA, Cabana MD, & Lynch SV (2010). Role of the gut microbiota in defining human health. Expert review of anti-infective therapy, 8 (4), 435-54 PMID: 20377338
Cerf-Bensussan N, & Gaboriau-Routhiau V (2010). The immune system and the gut microbiota: friends or foes? Nature reviews. Immunology, 10 (10), 735-44 PMID: 20865020
Benson AK, Kelly SA, Legge R, Ma F, Low SJ, Kim J, Zhang M, Oh PL, Nehrenberg D, Hua K, Kachman SD, Moriyama EN, Walter J, Peterson DA, & Pomp D (2010). Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proceedings of the National Academy of Sciences of the United States of America, 107 (44), 18933-8 PMID: 20937875