A recent study led by Dr. Luis Fontana (Department of Biochemistry and Molecular Biology II and Institute of Nutrition and Food Technology “José Mataix”, University of Granada, Granada, Spain) has found that administration of Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036 may downregulate gut inflammatory genes in obese rats. Rats were divided into various groups to receive either a placebo, L. paracasei CNCM I-4034, B. breve CNCM I-4035, L. rhamnosus CNCM I-4036, or a combination of L. paracasei CNCM I-4034 and B. breve CNCM I-4035.
Dr. Luis Fontana and Dr. Ángel Gil, co-authors of the study, corresponded with GMFH editors about the significance of the work.
Current research has been focusing on the gut as a new target for inflammatory conditions, such as insulin resistance syndrome. What is your previous experience in studying the role of the intestinal epithelium and gut microbiome in inflammatory-related conditions?
Our research group has worked for the last 15 years with metabolically unhealthy obese children, which exhibit features of insulin resistance syndrome and pro-inflammatory conditions. In these children, the gut microbiome is altered. In obese and diabetic Zucker rats, which show a pro-inflammatory status associated with an altered pattern of cytokine secretion in several tissues, we have reported that giving probiotics for one month resulted in an improvement of liver steatosis and decreased levels of plasma lipopolysaccharide, a well-known microbial substance that may translocate the intestine into chylomicrons.
What does your newest study add?
There are two main findings of our last study. First, expression of three inflammation-related genes is increased in the intestinal mucosa of genetically obese Zucker rats compared with the lean rats. Second, probiotic administration down-regulated expression of those genes. The effect was in part mediated by a decrease in both macrophage and dendritic cell populations.
What is the specific mechanism of action of the three probiotic strains assessed? At which levels do they act?
We propose a mechanism of action of these three probiotics in our last paper. Briefly, administration of L. paracasei CNCM I-4034, B. breve CNCM I-4035 and L. rhamnosus CNCM I-4036 induces changes in gut microbiota composition, which translate into a greater secretion of IgA and the turning off of inflammatory genes (Adamdec1 and Ednrb). These changes would result in less bacterial translocation in the intestine and, accordingly, in lower concentrations of LPS-LBP in serum. This, in turn, would have a less severe impact both in the liver and in the white adipose tissue. These two organs would respond by decreasing their production of IL-6 and TNF-α. In fact, we have previously reported low plasma levels of these two proinflammatory cytokines in the Zucker rat model after treatment with the abovementioned probiotics.
Based on your study, do you think that gut microbiome modulation through probiotics could decrease insulin resistance syndrome and its comorbidities in humans?
We definitely do. In a previous work we showed that administration of our strains to obese Zucker rats diminished hepatic steatosis, the liver component of the insulin resistance syndrome. We need to be very clear, though: probiotics are not going to cure the syndrome or any other disease; but at the very least they will serve as an adjuvant treatment.
What further steps is your research group planning to take in the way of targeting the gut microbiota for the management of inflammatory conditions?
The three strains have been thoroughly characterized in preclinical studies. We have even carried out a randomized, placebo-controlled clinical trial with healthy volunteers to study the safety of the strains. Clearly, our next step must be a clinical study with patients affected by gut-related diseases. We also have breast cancer and asthma in mind.
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