A study by a team of researchers from the Biomolecular Chemistry Institute of the National Research Council of Italy (Cnr-Icb) published in the journal EMBO Molecular Medicine reveals that the intestinal microbiota and its relationship with endocannabinoids are important players in counteracting inflammatory and muscle-degenerative processes such as those characterizing Duchenne muscular dystrophy
In the medical field, the term myopathies refers to a group of rare or extremely rare disorders causing progressive and irreversible degeneration of skeletal muscles. Among the hereditary myopathies, i.e. caused by mutations occurring in the DNA that are transmitted from parents to children, Duchenne muscular dystrophy (DMD) is the most frequent and detrimental form. The onset of the disease often appears from the first years of life and unfortunately, as for many other rare diseases, effective treatments are not yet available.
A new discovery was reported in a scientific article published in the prestigious scientific journal EMBO Molecular Medicine by a team of researchers working at the National Research Council of Italy (Cnr) coordinated by Fabio Arturo Iannotti and Vincenzo Di Marzo. The discovery by Iannotti and colleagues demonstrates that the composition and function of specific families of symbiotic bacteria (commonly defined as “good bacteria”) living and thriving in our intestine are necessary for the well-being of the organism. As a consequence, alterations of the gut microbiota, a condition defined as dysbiosis, along with the altered production of specific substances such as butyrate, represent a pathological mechanism participating in triggering inflammatory and muscle-degenerative processes in Duchenne.
“To date, the number of scientific works showing that the diversity and function of the intestinal microbiota play a key role in numerous functions in our body is constantly expanding. However, still little is known about the chemical signals underlying the communication between the intestine and skeletal muscles. While the role of the intestinal microbiota in skeletal muscle diseases was fully unknown“, says Iannotti.
In addition, the discovery sheds light on the importance of butyrate in regulating the production and function of another important class of endogenous molecules called -Endocannabinoids- whose altered function plays an important role in promoting inflammatory and muscle-degenerative processes.
“Endocannabinoids refer to a large group of molecules which in our body are produced to regulate many functions of the body. Among them, two main lipid mediators known as Anandamide and 2-Arachidonoylglycerol are the two major players. Since their identification in the early 90s of the last century, it has become suddenly evident that both AEA and 2-AG play an important role in maintaining the health of the organism. Therefore, alterations of endocannabinoids have been described in a large number of human pathologies. And also in this case our research group by carrying out pioneering studies has recently demonstrated that the endocannabinoid 2-Arachidonoylglycerol plays a key role during the formation and development of skeletal muscle from the early stages of embryonic development, and also that the pharmacological inhibition of the CB1 endocannabinoid receptor represents a promising therapeutic strategy against muscle deterioration as demonstrated in a mouse model of DMD” continues Dr Iannotti.
This study was achieved thanks to the support of the International Mixed Unit (UMI), an institution founded and scientifically coordinated since 2016 by Vincenzo Di Marzo with the aim of promoting scientific bilateralism between the Cnr and the Université Laval in Quebec, Canada by studying the impact of nutrition and the gut microbiota in human pathologies.
The research also involved the Department of Pharmacy of Federico II University and the experimental research centre Charité Universitätsmedizin and Max Delbrück in Berlin.
Fabio Arturo Iannotti