A research team led by scientists from the State University of Campinas (UNICAMP) in São Paulo, Brazil, has made significant progress in understanding the relationship between the gut microbiome and enterocytes.
Research published in journals intestinal microorganismsshowed how the microbiome and the compounds it produces, such as butyrate, influence the function of the cells lining the large intestine. This intestinal layer is in close contact with bacteria and produces mucus that contributes to its barrier function and prevents bacteria from entering the body.
Among the discoveries is a description of the dual function of cells previously thought to be solely responsible for secreting mucus. The researchers found that these cells also absorb nutrients, and their amounts in the epithelium are regulated by signals from the gut microbiome. When the gut microbiome decreases, the number of these cells increases.
The abundance of these cells is controlled by the production of butyrate, a compound resulting from the fermentation of dietary fiber, and its receptor, GPR109A. The more butyrate produced, the fewer these cells will be.
This study paves the way for a deeper understanding of the role of the microbiota and its metabolites in conditions such as inflammatory bowel disease and the development of treatments. Additionally, this study shows how the integrity of the intestinal wall can change, especially in older adults.
“When the microbiota is reduced, the large intestine, which under normal conditions favors mucus production, begins to develop properties associated with the absorption of nutrients normally associated with the small intestine. We do not yet know why this occurs, but this change is associated with the expansion of dual-function cells and may represent an adaptive response to the reduction of bacteria in this part of the intestine,” explains Vinicius Díaz Nirello, lead author of the study. Nirello conducted this research while a doctoral student at the Institute of Biological Sciences (IB-UNICAMP) with a scholarship from FAPESP.
“We observed that these dual-function cells are reduced by butyrate and its receptors. However, in the context of dysbiosis, when there is a decrease in bacteria due to antibiotic use or the aging process, this cell population expands. We speculate that this is an adaptive response aimed at strengthening the intestinal barrier,” added Marco Vignolo, professor at IB-UNICAMP and co-advisor of Nirello’s doctoral research with Patrick. Varga Wise is a professor at the University of Essex in the UK and a researcher at UNICAMP.
This study reveals a previously unknown level of plasticity in the intestinal epithelium that is governed by microbial triggers.
Vinolo and Varga-Weisz received support from FAPESP for their research through four projects (17/16280-3, 18/15313-8, 23/14946-5, and 19/16113-5).
cells and microbiota
To reach these results, the researchers treated groups of mice with a cocktail of antibiotics for three days, sharply reducing the gut microbiome. Mice in the control group received only a harmless solution to keep their microbiota intact.
In addition to these mice, the researchers also used other germ-free animals that were born and raised without a microbiome. These animals were divided into two subgroups and received a dose of bacteria from the intestines of young humans (18-35 years) or older adults (65 years and older). The aim was to investigate the influence of microbiota based on donor age.
The researchers also analyzed biopsies, or small tissue samples, taken from the colons of young and old people to assess the effect of aging on the number of cells that make up the intestinal epithelium.
Mouse samples were analyzed using single-cell transcriptomics technology, which analyzes each cell’s response individually. This method allowed the researchers to more deeply examine the individual characteristics of the cells that make up the intestinal epithelium. These cells include enterocytes, which absorb nutrients, water, and electrolytes, and goblet cells, which secrete mucus.
The researchers observed that a specific population of cells previously classified only as mucus-secreting may also perform absorptive functions. “These cells express genes for both functions, which was previously thought not possible in this cell type. Because this population responds directly to the microbiota, this finding suggests a previously unknown adaptation of the intestinal epithelium,” Nirello explains. This cell population is more prevalent in the colon of older adults, as shown by human biopsies and mice that have bacteria from this cell population in their colons.
New experiments that delete secretory or uptake genes in these cells could help clarify their roles. This will advance our understanding of intestinal diseases and their treatments.
sauce:
São Paulo Research Foundation (FAPESP)
Reference magazines:
Historical changes, geographic biases, and biological constraints shape the discovery of mammalian species. intestinal microorganisms. DOI: 10.1111/jse.70040
