Fresh off Michael Pollan’s New York Times magazine feature on microbiomes – the totality of microbes, their genomes and particular environments, such as the human digestive tract — new research has shown mixed potential for diet in reducing the risk of E. coli O157:H7 infection, at least in mice.
Research on microbiomes has been around for awhile, but as humans, we’re limited in understanding how to strategically lever gut activity to reduce the risk of foodborne illness.
A cocktail of non-pathogenic bacteria naturally occurring in the digestive tract of healthy humans can protect against a potentially lethal E. coli infection in animal models according to research presented today at the 113th General Meeting of the American Society for Microbiology. The research, conducted by scientists at the University of Michigan Medical School in Ann Arbor, could have important implications for the prevention or even treatment of this disease.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a food-borne pathogen that has been responsible for several recent outbreaks of potentially fatal disease. Severe manifestations of this disease include both hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS), a form of acute renal disease that can result in death or permanent disability.
“EHEC is of primary concern because HUS, the most severe outcome, preferentially targets young children,” says Kathryn Eaton, a researcher on the study. “Tragically, HUS occurs late in the course of disease, often after the child has recovered from the enteric form. Thus, children who appear to have recovered may relapse and even die.”
HUS is caused by absorption of Shigatoxins (Stx) that are produced by the bacteria in the intestine. Stx production occurs within a few days of bacterial colonization and once it is present in the intestines it can be absorbed into the bloodstream where it may cause systemic disease and even death. There is no specific treatment or preventative measure that prevents progression from HC to HUS.
The overall goal of research in Eaton’s laboratory is to identify potential therapies to prevent production or absorption of Stx before it can cause disease.
“In brief, the results of our study show that in a mouse model, non-pathogenic bacteria that are normal inhabitants of the human intestine can eliminate Stx from the intestinal contents and completely prevent HUS,” says Eaton.
In the study, the researchers gave EHEC to two groups of mice: one that had been been pre-colonized with a mix of bacterial species derived from normal human intestines and one that had not. In the pre-colonized mice, Stx levels remained undetectable and all mice remained completely healthy. In contrast, the control group had high levels of Stx and all developed kidney disease within one week of infection.
“The discovery that normal intestinal bacteria can prevent intestinal Stx accumulation and disease in an animal model may have important implications for prevention of HUS in people infected with EHEC,” says Eaton.
First, it could help explain why not everyone infected with EHEC develops HUS. Second, and most importantly says Eaton, it identifies specific, non-pathogenic, probiotic bacteria that could be used to prevent or treat Stx-mediated diseases
Zumbrun, et al, of the Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, write in today’s PNAS that “dietary fiber content affects susceptibility to Shiga toxin (Stx)-producing Escherichia coli (STEC) infection in mice. We showed that high fiber diet (HFD)-fed mice had elevated levels of butyrate, a beneficial gut metabolite that paradoxically enhances the cell-killing capacity of Stx. We also found that the amount of gut bacteria in HFD-fed mice increased whereas the percent of commensal Escherichia species (spp) decreased compared with animals fed a low fiber diet (LFD). These changes led to higher E. coli O157:H7 colonization levels, more weight loss, and greater rates of death in HFD-fed than in LFD-fed STEC-infected animals.
The likelihood that a single individual infected with the Shiga toxin (Stx)-producing, food-borne pathogen Escherichia coli O157:H7 will develop a life-threatening sequela called the hemolytic uremic syndrome is unpredictable. We reasoned that conditions that enhance Stx binding and uptake within the gut after E. coli O157:H7 infection should result in greater disease severity. Because the receptor for Stx, globotriaosylceramide, is up-regulated in the presence of butyrate in vitro, we asked whether a high fiber diet (HFD) that reportedly enhances butyrate production by normal gut flora can influence the outcome of an E. coli O157 infection in mice. To address that question, groups of BALB/c mice were fed high (10%) or low (2%) fiber diets and infected with E. coli O157:H7 strain 86-24 (Stx2+). Mice fed an HFD exhibited a 10- to 100-fold increase in colonization, lost 15% more body weight, exhibited signs of morbidity, and had 25% greater mortality relative to the low fiber diet (LFD)-fed group. Additionally, sections of intestinal tissue from HFD-fed mice bound more Stx1 and expressed more globotriaosylceramide than did such sections from LFD-fed mice. Furthermore, the gut microbiota of HFD-fed mice compared with LFD-fed mice contained reduced levels of native Escherichia species, organisms that might protect the gut from colonization by incoming E. coli O157:H7. Taken together, these results suggest that susceptibility to infection and subsequent disease after ingestion of E. coli O157:H7 may depend, at least in part, on individual diet and/or the capacity of the commensal flora to produce butyrate.