When mice were raised germ-free, then given a transplant of human gut microbes, the impact of fiber on their colons could be seen. Mice fed a high-fiber diet maintained a thick mucus layer along the lining of their colons, while those that received a fiber-free diet saw the mucus layer grow thinner as bacteria capable of digesting mucus proliferated. The thin layer allowed a pathogen bacteria access to the cells of the colon wall. Credit: University of Michigan
It sounds like the plot of a 1950s sci-fi movie: normal, helpful bacteria that begin to eat their host from within, because they don’t get what they want. But new research shows that’s exactly what happens when microbes inside the digestive system don’t get the natural fiber that they rely on for food. Starved, they begin to munch on the natural layer of mucus that lines the gut, eroding it to the point where dangerous invading bacteria can infect the colon wall.
An international team have shown the impact of fiber deprivation on the guts of specially raised mice. The mice were born and raised with no gut microbes of their own, then received a transplant of 14 bacteria that normally grow in the human gut. Scientists know the full genetic signature of each one, making it possible to track their activity over time. The findings have implications for understanding not only the role of fiber in a normal diet, but also the potential of using fiber to counter the effects of digestive tract disorders.
Using U-M’s special gnotobiotic, or germ-free, mouse facility, and advanced genetic techniques that allowed them to determine which bacteria were present and active under different conditions, they studied the impact of diets with different fiber content – and those with no fiber. They also infected some of the mice with a bacterial strain that does to mice what certain strains of E coli can do to humans – cause gut infections that lead to irritation, inflammation, diarrhea and more.
The result: the mucus layer stayed thick, and the infection didn’t take full hold, in mice that received a diet that was ~15% from minimally processed grains and plants. But when they substituted a diet with no fiber in it, even for a few days, some of the microbes in their guts began to munch on the mucus. They also tried a diet that was rich in prebiotic fiber – purified forms of soluble fiber similar to what some processed foods and supplements currently contain. This diet resulted in the same erosion of the mucus layer as observed in the lack of fiber.
They also saw the mix of bacteria changed depending on what the mice were being fed, even day by day. Some species of bacteria in the transplanted microbiome were more common – meaning they had reproduced more – in low-fiber conditions, others in high-fiber conditions. And the 4 bacteria strains that flourished most in low-fiber and no-fiber conditions were the only ones that make enzymes that are capable of breaking down glycoproteins that make up the mucus layer.
In addition to looking at the of bacteria based on genetic information, they could see which fiber-digesting enzymes the bacteria were making. They detected more than 1,600 different enzymes capable of degrading carbohydrates – similar to the complexity in the normal human gut. Just like the mix of bacteria, the mix of enzymes changed depending on what the mice were being fed, with even occasional fiber deprivation leading to more production of mucus-degrading enzymes.
Images of the mucus layer, and the “goblet” cells of the colon wall that produce the mucus constantly, showed the layer was thinner the less fiber the mice received. While mucus is constantly being produced and degraded in a normal gut, the change in bacteria activity under the lowest-fiber conditions meant that the pace of eating was faster than the pace of production – almost like an overzealous harvesting of trees outpacing the planting of new ones.
When the researchers infected the mice with Citrobacter rodentium – the E. coli-like bacteria – they observed that these dangerous bacteria flourished more in the guts of mice fed a fiber-free diet. Many of those mice began to show signs of illness and lost weight. When the scientists looked at samples of their gut tissue, they saw not only a much thinner or even patchy mucus later –they also saw inflammation across a wide area. Mice that had received a fiber-rich diet before being infected also had some inflammation but across a much smaller area.
Going forward, Martens and Desai intend to look at the impact of different prebiotic fiber mixes, and of diets with more intermittent natural fiber content over a longer period. They also want to look for biomarkers that could tell them about the status of the mucus layer in human guts – such as the abundance of mucus-digesting bacteria strains, and the effect of low fiber on chronic disease such as IBD.
Martens said. “Your diet directly influences your microbiota, and from there it may influence the status of your gut’s mucus layer and tendency toward disease. But it’s an open question of whether we can cure our cultural lack of fiber with something more purified and easy to ingest than a lot of broccoli.” http://www.uofmhealth.org/news/archive/201611/high-fiber-diet-keeps-gut-microbes-eating-colon%E2%80%99s-lining
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