Bacteria Offers Solution to Inflammation

Mutualism, the symbiotic relationship between individuals of different species in which both individuals benefit from the association, is a common finding when looking at gut bacteria. Often it is the case that a host microbiome, will aid in the digestion of particular foods; bacteria can thrive in this environment, and it helps the host process their diet. In a study recently published by researchers at the University of Oregon, a mutualistic relationship between gut bacteria and zebrafish is observed.

Researchers identify a new protein called Aeromonas immune modulator (AimA), which is secreted by a gut bacterium in zebrafish. The protein is found to reduce inflammation in the gut and even put a stop to septic shock. The study appears in the journal eLife, devoted to mechanistic microbiome studies.

The researchers asked themselves, how can there be coexistence between microbiome bacteria and host without damaging inflammation. To determine the answer to their question they looked at whether gut bacteria actively secrete factors that prevent an excessive inflammatory response. Zebrafish proved to be easy to work with test subject due to its flexibility in testing and its ability to offer an unbiased approach.

Upon discovery of the new protein, AimA, the researchers characterized its amino acid sequence. Interestingly, the amino acid sequence is unlike any they may have predicted. To determine the 3D structure of the protein in an attempt to characterize it further, protein crystallography was performed. The 3D structure revealed a striking similarity to a class of proteins known as lipocalins. Lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids and lipids. Additionally, lipocalins include members that modulate inflammation in humans.

"That structural similarity suggested to us that the bacterial protein may function as the human protein" Guillemin, co-author and Professor of Biology at UO said. "In particular, rather than doing something specific to counteract inflammation caused by one kind of bacteria, maybe it was doing something more generally to temper the host's immune response."

When the research team created inflammation in the zebrafish, they observed as AimA reduced the inflammation in return. The group even created septic shock in the zebrafish and witnessed as the AimA protein mitigated the shock, extending the life of the organism.

The team turned their focus to AimA-deficient zebrafish to determine differences in response to inflammation. AimA-deficient zebrafish were not able to fend off the inflammation as well as their AimA-producing counterparts.  In addition, the bacteria also fared worse in the AimA-deficient hosts.

"The bacteria were experiencing this inflammation, which is detrimental to them," Guillemin remarked.  "Inflammation involves the production of antimicrobial compounds like reactive oxygen species that are designed for clearing bacteria, so, now, a beneficial bacterium is going to be at a disadvantage if it's experiencing too much of this inflammatory response."

This study highlights the potential prospects for human inflammatory diseases. The team hopes to one day see their research applied to treatments and cures for inflammatory diseases. Guillemin comments, "These resident gut microbes are motivated to inhibit inflammation, and they probably have lots of creative ways of dampening down our immune system. We can learn a lot from them about how to design novel anti-inflammatory therapies."

Sources: eLife, Science Daily, YouTube