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Dutch Team Finds Gut Transcriptional Changes Tied To Probiotic Bacteria Intake

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – Ingesting probiotic bacteria can alter the transcriptional patterns in the human gut, according to a study set to appear online in the Proceedings of the National Academy of Sciences this week.

Dutch researchers did a double-blind crossover study in which seven participants each received three lactobacillus bacteria supplements — given individually every two weeks — and a placebo control. They then used microarrays to gauge and compare transcriptome patterns in small intestine mucus samples within and between individuals after each treatment.

In the process, the team found differential gene expression patterns associated with probiotic intake — including changes in the levels of some genes involved in immune function, cell cycle, and other pathways that are apparently altered in human cell lines response to some drugs.

Though the study involved a relatively small group of individuals, senior author Michiel Kleerebezem, a researcher affiliated with the Top Institute Food and Nutrition partnership, NIZO Food Research, and Wageningen University, and co-authors argued that the work could serve as one of "the first steps to investigate the interplay between microbiota, probiotic, or other nutritional supplements and human genetics [to] personalized nutrition."

Metagenomic studies have started making headway towards understanding how microbes on and in the body affect human health and disease. For instance, the researchers noted, recent research has identified links between gut microbes and processes such as energy use and obesity. Of particular interest to many are so-called probiotic bacteria, which are garnering interest in the food industry and beyond based on their potential health benefits.

"Probiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function through largely unknown molecular mechanisms," Kleerebezem and his colleagues explained.

In an effort to delve into the effects of these bacteria, if any, the team compared transcriptome patterns in the guts of healthy participants given Lactobacillus acidophilus, L. casei, L. rhamnosus, or placebo.

Each of the seven participants ate preparations containing one of the probiotic species or placebo. Six hours later, the team collected small intestine mucus samples and assessed transcriptional patterns in these samples using Affymetrix Human Genome U133 Plus 2.0 arrays.

As part of the crossover study design, individuals received a different treatment every two weeks over roughly a month and a half.

Indeed, the team reported, ingesting the probiotic bacterial species led to changes in the expression of hundreds — and in some cases thousands — of genes. The specific gene expression patterns varied from one individual to the next, they explained, as did the extent and type of transcriptional change following probiotic intake.

"[W]e found that transcriptomes clustered per person, not per intervention," the researchers wrote, "showing that person-to-person variation in gene expression was the largest determinant of differences between transcriptomes."

Even so, the team did home in on some shared pathways and processes that appear to be altered following the intake of probiotic bacteria.

For instance, they noted, L. acidophilus ingestion was linked to increased expression of several immune genes, including those coding for interleukin-1-beta and related proteins, as well as genes involved in insulin production, metabolism, and more.

Meanwhile, L. casei and L. rhamnosus consumption were associated with differential expression of homeostasis/metabolism, immune function, and cell growth, development, and signaling-related pathways, among others.

In addition, the team found that many of the genes that get differentially expressed after probiotic consumption overlap with those expressed at different levels in cell cultures treated with certain drugs or bioactive compounds.

Although they conceded that more research on a larger number of individuals is needed to confirm their findings, the team speculated that a more complete understanding of probiotic effects on gene expression could ultimately offer insights into using such bugs to treat certain gastrointestinal problems. Moreover, they noted, such work might offer a window into health intestinal profiles and related biomarkers.

"These comprehensive and comparative analyses may guide the design of rational strain-specific clinical tests involving application of probiotic supplementation in humans," they noted, "possibly including persons suffering from specific intestinal conditions."