AsianScientist (Jul. 15, 2013) – Japanese scientists report that an orally-administered cocktail of 17 human-derived bacteria strains reduces inflammation and allergic responses in the guts of mice. The Clostridia bacteria could potentially be used in oral probiotic therapies for human inflammatory disorders, the researchers say.
Scientists and clinicians have had some success in treating inflammatory and allergic gut diseases by manipulating the intestinal microflora – fecal transplants, for example, have been very effective against severe gut infections. Stool contains hundreds of bacterial species, however, and scientists have yet to figure out which are really therapeutic.
In an attempt to systematically identify bacteria with robust protective effects, Dr. Kenya Honda and colleagues at the RIKEN Center for Integrative Medical Sciences in Japan took a stool sample from a healthy human volunteer and orally administered it to mice. Reporting in the journal Nature, the researchers found increased numbers of regulatory T cells – immune cells that suppress excessive immune system activation, maintaining it at a healthy level – in the colons of animals that had received the stool.
To isolate strains that were responsible for activating the regulatory T cells, the researchers cultured the bacteria that had managed to gain a foothold in the mouse gut, and identified them by sequencing. They selected 17 genetically diverse Clostridia strains from the panel they identified, and again fed them to mice. The mix of 17 strains induced regulatory T cells to levels comparable to those seen with whole stool, and was also able to reduce the severity of disease in mouse models of allergic diarrhea and colitis.
How does this bacteria cocktail activate regulatory T cells? The researchers think that the 17 strains are a source of short-chain fatty acids, bacterial antigens, and other factors that help the cells differentiate, expand in number, and home to the colon to tamp down the immune response there.
Interestingly, the researchers saw that the protective effect of the 17-strain cocktail was greatly diminished when mice were treated with each strain individually, or even with combinations of up to five strains. This suggests that a diverse microbial community, with multiple species performing different functions, is needed for a healthy gut.
While some Clostridia species are human pathogens, the researchers’ sequencing analysis showed that none of their strains carry any genes encoding toxins or other virulence factors. It remains to be seen if these human-derived bacteria will have similar protective effects in the human gut, but there is an encouraging piece of evidence.
By comparing their findings with data from previous studies, the researchers found that a number of their strains had been found to be less prevalent in patients with inflammatory bowel disease, suggesting that supplementing them with the strains may be an effective therapy.
The article can be found at: Atarashi et al. (2013) Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota.
Source: Nature. Photo: PNNL – Pacific Northwest National Laboratory/Flickr/CC.
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