Gut Bug, Bad Bug

Lactobacillus acidophilus

Lactobacillus acidophilus (Photo credit: AJC1)

Helicobacter pylori, Gastric Mucosa, H&E Dozen...

Helicobacter pylori, Gastric Mucosa, H&E Dozens of the curved bacteria fill the lumen of a gastric foveola. Hematoxylin & eosin stain, 1000X. 

Helicobacter pylori bacteria

Helicobacter pylori bacteria.

We usually associate bacteria that infect our gut us with illness. Good bugs that colonise our gut may actually protect us from those with more malicious intent.
Human gut micro-organisms are traditionally associated with often devastating intestinal disease, but there is increasing evidence they also play a major role in human health. Harnessing the protective power of the good bugs may help prevent illness and prevent bad bugs from causing disease.

The statistics are staggering in terms of the morbidity and mortality with respect to gut bacterial disease.
Diarrhoea is a major cause of death globally and the outbreak of cholera among refugees during the recent Rwandan crisis was a staggering estimated 70,000 individuals with 4,000 deaths. This was entirely preventable as there is a very cheap oral vaccine available.

Similarly with increased hygiene Helicobacter pylori infections have decreased dramatically in the West but are rising dramatically in some countries with a rapid rise in gastric cancer incidence likely as a consequence. Again this is preventable infectious disease.

The strange thing about H. pylori is that, although there are a number of strains of the bacteria with some more virulent than others and some causing more severe ulceration and increasing the risk of cancer (type 1), the bacteria seems to live in many people and cause no harm or symptoms. Even more significant is that some strains seem to be protective. So certain bacteria or certain strains of bacteria may be protective when other similar strains are harmful to humans.

This triggered the notion that there are bacteria in the human GI tract that are commensals, and potentially beneficial towards human health.

This means there is the potential to how transform foods into more functionally beneficial forms through inoculating certain foods with for example lactobacilli.
Lactobacilli colonise for a long time and have an anti-inflammatory action. It is not known how lactobacilli exert their effects and research is hampered by the complexity of the gut microbiota but there seems to be a protective effect. Lactobacilli and bifidobacteria are two organisms that have already shown shown promise as probiotics. For example, Lactobacilli have been used to reduce C. difficile infection in hospitals after administration of antibiotics.

Research into what are good or beneficial gut bugs is hampered by the fact there is a vast excess of microbial cells in the body compared with human cells.
To get a handle on how the human gut biota can impact human intestinal dysfunction it is important to get a handle on the great diversity of the 10 times more bacterial cells in the human body than human cells and the associated 100 times more bacterial than human genes.

But we understand many of these organisms very poorly because most are anaerobic and are very difficult to culture.

Using specific genomic techniques it has been possible to use a reductionist approach and then extrapolate upwards to estimate the constituent bacteria in the human gut.

The numerically predominant organisms include the bacteroides, which make up about 40% of the typical microflora of an adult, and the important firmicutes, which make about 10% and include the clostridia and the lactobacilli.

Bacteria are responsible for most of the digestive metabolic conversion in the gut including production of things like vitamins and cofactors. There are four times more bacterial genes than human genes responsible for carbohydrate metabolism in the human gut. There are six times more responsible for amino acid metabolism.

From animal studies, germ free animals gain weight more slowly. So the bugs in the gut are related to weight gain. Studies in a mouse model of obesity with a leptin mutation have shown differences in lean and obese animals. There is a predominance of firmicutes in obese animals. The firmicute enriched microbiota is more efficient at extracting calories from the diet and making them more readily available for the host.

In obese humans on calorific restriction diets, when they lose weight there is a more normalized rate of firmicutes to bacteroides.

The evidence is mounting that the composition of the gut microbiota and perhaps the ratio of the individual microbial components may be an important contributor to disease related to immune gut problems and GI dysfunction.

In IBD, in particular in Crohn’s disease, it has been found that some members of the firmicuture group are deficient. Similarly the finding that certain microbiological groups are missing in the microbiota of some individuals with IBS indicate it might contribute to pathology.

The potential ways an organism could impact on the gut microbiota include:
• Competition for substrates.
• Direct antagonism by inhibitory substrates.
• Competitive exclusion.
• Altering host mediated effects such as improved barrier function.
• Altering host immune response.
It is naïve and impossible to think that you can really understand the biology of a single organism interacting with the host and ignore the complex ecosystem in which that organism is going to reside.

The use of probiotics or specially inoculated functional foods to alter the milieu of an infection may become a new therapeutic strategy in the near future.

Conor Caffrey writes on health, medicine and science.


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