The development of food allergies is a growing concern, and recent evidence suggests that imbalances in the gut microbiome might play a significant role. These imbalances can create inflammation in the intestinal tract, fostering an environment that is more susceptible to food allergies.
New research from Cathryn Nagler’s lab at the University of Chicago Biological Sciences Division (BSD) and Pritzker School of Molecular Engineering (PME) has unveiled a promising interaction between a specific microbial species and the prebiotic lactulose. Together, they promote the production of butyrate, a metabolite known for its beneficial effects on gut health.
“Butyrate is a four-carbon molecule that has huge effects in the gut… this could have broad impacts for food allergies,” said Nagler, the Bunning Family Professor. This discovery could lead to the development of synbiotic therapies that address microbiome dysbiosis rather than merely treating allergic reactions to specific allergens.
The Study’s Methodology
Nagler’s team investigated the impact of a combination of the bacterium Anaerostipes caccae and the prebiotic lactulose on butyrate production in the gut. Their study, published in Cell Host & Microbe, involved treating mice with this combination and observing its effects on allergic responses to cow’s milk.
Researchers collected data from 894 participants at two prenatal obstetric clinics in New York between 2009 and 2017. The study included a comprehensive review of medical records and interviews, focusing on variables such as maternal weight, race, age, education, marital status, nicotine use, and prior spontaneous abortion.
Key Findings
The study revealed that treating mice with a mixture of A. caccae and lactulose significantly increased butyrate levels in their intestinal tracts, which in turn suppressed allergic responses to cow’s milk.
“We know [from scientific literature] that butyrate can improve barrier integrity [of the intestinal tract] and induce broad anti-inflammatory effects,” said Ande Hesser, the first author of the paper and a former Ph.D. student in Nagler’s lab. The body relies on the gut microbiome to produce butyrate, as it cannot do so on its own.
The Role of the Gut Microbiome
The primary function of gut microbiota is to digest dietary fiber, which humans are unable to break down themselves. This co-evolutionary relationship allows bacteria to produce key metabolites, such as butyrate, through fermentation processes that prevent inflammation and enhance overall gut health.
Modern Challenges
Today’s environments present new challenges to this ancient partnership between humans and their gut microbiomes. Factors such as antibiotic use, high-fat and low-fiber diets, decreased exposure to infectious agents, cesarean births, and formula feeding can reduce gut microbiome diversity, leading to imbalances compared to our evolutionary past.
Previous Research Insights
Nagler’s previous research, published in Nature Medicine, found that A. caccae, a potent producer of butyrate, was more abundant in the gut microbiomes of healthy infants compared to those with cow’s milk allergy (CMA). This bacterium was significantly associated with changes in gene expression in the intestinal epithelium, a layer of cells lining the intestines.
Despite making up only about 1% of the typical gut microbiome, A. caccae plays a crucial role in butyrate production. Understanding this bacterium’s molecular functions required isolating and culturing it in the lab, a challenging task due to its low abundance and strict anaerobic environment requirements.
Experimentation and Results
Isolation and Culturing
Hesser, during her Ph.D. research, isolated A. caccae from a fecal sample of a healthy infant, genetically profiling and culturing it in an anaerobic chamber. The team then tested whether this strain could colonize a cow’s milk allergy model in gnotobiotic mice, which are germ-free and engrafted with specific microbes for research purposes.
Colonization and Butyrate Production
After colonizing mice with donor feces from an infant with CMA, some mice were fed A. caccae LAHUC, while others received a sterile control. Although A. caccae thrived and increased in abundance for up to a month after treatment, initial tests showed no significant effect on butyrate levels. The researchers hypothesized that the CMA mouse microbiome might lack a key element needed for A. caccae to thrive and produce butyrate, potentially a prebiotic.
Synbiotic Combination
Hesser screened over a dozen prebiotics to identify one that could stimulate butyrate production in the presence of other fecal bacteria. The breakthrough came with lactulose, a synthetic sugar that significantly boosted butyrate production. When administered to the mouse model of cow’s milk allergy, the combination of A. caccae and lactulose increase
