Gut Microbes Guard Mice Against Sepsis – Latest Research
The CDC defines Sepsis as the body’s extreme response to an infection. It is life-threatening, and without timely treatment, sepsis can rapidly cause tissue damage, organ failure, and death.
Previously, IgA responses have been linked to gut microbes and IgA specific to components of intestinal bacteria have been detected in sera of mice. But the mechanisms underlying the induction of serum IgA and its role in host protection remain uncertain. Additionally, prior work has indicated that immunoglobulin M (IgM) antibodies quickly respond to blood-borne bacteria in sepsis and that gut microbes trigger immunoglobulin G (IgG) antibody responses that can block bacterial infection.
Now, researchers at the University of Pennsylvania have demonstrated how gut microbes, linked to IgA, could offer a solution for the treatment of sepsis.
The researchers found that exposing mice to a unique but natural microflora that included several members of the Proteobacteria phylum led to increases in IgA levels in the blood. Moreover, shifting the mouse gut to a Proteobacteria-rich microbiota led to IgA-mediated resistance to sepsis in mice.
“We propose that serum IgA and IgG antibodies may play roles similar to the protective role proposed for natural IgM antibodies, with the IgA component providing a non-inflammatory mechanism for keeping invading bacteria in check,
” says first author Joel Wilmore of the Perelman School of Medicine at the University of Pennsylvania.
The investigation involved the transfer of blood that lacked IgA to mice with sepsis. It was seen that all but one animal died within two days. By contrast, mice that received blood enriched in IgA survived much longer.
Taken together, the findings suggest that commensal microbes can have a substantial impact on IgA levels in the blood, resulting in protection against bacterial sepsis.
“The study is limited by the fact that the microbiome in every person or animal is unique to some degree, and our study is in the context of the animal facility at the Perelman School of Medicine at the University of Pennsylvania,” Allman says. “While IgA protected mice in our study, it should not be assumed that IgA could replace standard treatments provided to patients in a clinical setting.“
