Microbiological in vivo production of CLNA as a tool in the regulation of host microbiota in obesity control

Metabolic disorders associated with dietary patterns have become a social and economic problem. Obesity is indeed considered a central feature that increases the risks associated with a vast array of diseases (insulin resistance, type 2 diabetes, fatty liver disease, atherosclerosis, hypertension, stroke, cancer, and asthma), with significant morbidity and mortality. Although lipids may be involved in the development of these illnesses, recent studies have stated their role as cellular mediators and they have been assayed as bioactive compounds in possible treatments. Clear examples are the conjugated isomers of linoleic acid (CLA), which have been associated with antiatherogenic, antioxidative, immunostimulation, and body fat reduction activities. Recently, increased interest in other conjugated PUFAs has emerged, linked to the health-promoting properties of conjugated linolenic acid isomers (CLnA) like C18:3 c9t11c15 (rumelenic acid, RLA). These fatty acids combine in the same molecule a double conjugated bond system with the n3 structure of linolenic acid (ALA; C18:3 c9c12c15) resulting in a high bioactive potential. Animal studies have revealed that CLnA regulates leptin production and increases β-oxidation in the liver thus reducing perirenal and epididymal adipose tissue. Elsewhere it was reported that RLA increased PPARα levels in adipocytes, which suggests that it is a candidate functional ingredient for use in the prevention of obesity, diabetes, and dyslipidemia. CLA and CLnA are natural fatty acids (FAs) mainly found in dairy products and beef, because they are produced as intermediates of the biohydrogenation pathway of PUFAs by ruminal bacteria. Therefore it is hypothesized that other microorganisms may also be able to produce CLA and conjugated FAs. Indeed, recent investigations demonstrated that it is possible to elaborate fermented dairy products containing CLA and CLnA produced by these bacteria. Other authors have identified Bifidobacterium strains with a high rate of substrate conversion to yield CLA, CLnA, and stearidonic acids producing these FAs in vivo, increasing the RA concentration in murine and pigs livers as well as DHA and EPA in mice adipose tissue. An important issue arises from these results: host fatty acid composition can be manipulated by oral administration of CLA-producing microorganisms. In the last 5 years an increasing number of studies have found strong evidence of the role not only of diet but also of human gut microbiota in the development of diabetes and obesity. Indeed, host microbiota regulates the content of triglycerides, cholesterol esters, sphingomyelin, and phosphatidylcholine in the plasma, liver, and adipose tissue as well as energy metabolites. This chapter will review the current state-of-the-art microbiological in vivo production of CLA and CLnA and its effect on host microbiota and health.