Evaluation of Evaluation of Prebiotic and Anti-Obesity Properties of Persian Gulf Brown Seaweeds on Induced Obese Male Ratsand anti-obesity properties of Persian Gulf brown seaweeds on induced obese male rats

 Obesity, as a serious metabolic syndrome, has many health and social effects disorder that is characterized by excessive accumulation of body fat. It’s also associated with a body mass index (BMI) of more than 30 kg/m2. Overeating, lack of physical activity, and genetic factors are the main reasons for obesity. Based on BMI analysis of the population of 200 countries, obesity will has exceeded 6% in men and 9% in women by 2025(1). Obese individuals are at risk of developing diseases such as type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, hypertension, hypercholesterolemia, immune dysfunction, rapid onset of infection, delayed wound healing, and certain types of cancers(2). The pathogenesis of these disorders has been linked to the health of the gut microbiota(3). The gut microbiota is considered an endocrine organ that has influenced on immunity, metabolism, neuroendocrine responses of the host, and synthesizes vitamins, amino acids, and enzymes(4). They can also produce important short-chain fatty acids (SCFA) and absorb dietary minerals(5). The microbiota composition is very different amongst people and is affected by several factors, such as antibiotic use, diet, lifestyle, genetic traits, and body mass index(6). It was demonstrated that a decrease in beneficial bacterial species in the gut microbiota is linked to obesity and metabolic disorders(7), so microbiota has been known as one of the principal causes of obesity(8, 9). In addition, recent findings have shown that Firmicutes and Bacteroidetes are two dominant phyla in human gut microbiota, and an increased Firmicutes/Bacteroidetes ratio is correlated with obesity(10). Some studies suggest that the consumption of probiotic substances and dietary fibers can beneficially alter the gut microbiome composition in a short time(11, 12).  Recently, a lot of attention has been paid to the use of natural products such as marine organisms with anti-obesity activities. Marine organisms, especially brown algae, are good dietary complements with prebiotics and anti-obesity potentials for those who want to lose weight.  They are widely used in the treatment of various diseases because of their several pharmacological activities(13). Consumption of marine seaweeds has risen considerably over the past decades because of their high nutritional compositions such as minerals, polyunsaturated fatty acids, and high dietary fibers(14). Brown algae have the potential anti-obesity agents such as fucoxanthin, phlorotannins, fucoidan, and alginates(13, 15). Alteration in lipid metabolism, suppression of inflammation, suppression of adipocyte differentiation and delay in gastric emptying are the ways that anti-obesity compounds from algae may involve(16). Besides, the potential benefits of brown seaweeds on the human body are related to dietary fibers that have prebiotic activities over the gastrointestinal tract (GIT) microbiota. Such fibers are non-digestible components that can selectively enhance beneficial microorganisms of the gut microbiota (17, 18). On the other hand, consumption of brown seaweeds can promote beneficial bacteria while reduce harmful species in the gut microbiota of rats(10). Brown seaweeds have a variety bioactive molecules such as, polysaccharides, polyunsaturated fatty acids, and polyphenolic compounds that play have the potential health benefits in regulating gut microbiota and therefore improving obesity(3). In fact, consumption of brown seaweed may exert an effective impact on gut health by acting as prebiotics, and promoting the growth of lactic acid bacteria that aid in the production of SCFA such as butyrate, propionate, and acetate(19). Kim et al (2018) showed that Laminaria japonica brown seaweed had a probiotic and anti-obesity effect on reducing of pathogenic bacteria level and increasing lactic acid bacteria level in gut-obese rats(20).  Regarding to these considerations, the objective of this study was to find the effects of hot water and ethanolic extracts of Persian Gulf brown algae, Padina pavonica and Cystoseira myrica on changing gut microbiota, some serum indices, food intake and weight loss in rats that fed with high-fat diet.

In this study, 100 male Wister rats in the weight range of 220±20 gr were selected and divided into 10 groups (8 treatment groups, one normal control group, and one obese control group). All animals except for normal group were fed with 60% cholesterol for 1 month. Each group was further treated with hot water (HW) and ethanolic (E) extracts of seaweeds for 8 weeks.  Then during the experiment, food intake and weight loss were measured weekly and daily, respectively, and at the end of period, we collected the stool samples (3 samples of each group), and analyzed the intestinal microorganisms through 16SrRNA sequencing in all groups.

Our results indicated that the consumption of Padina pavonica and Cystoseira myrica brown seaweeds can change obese rats' intestinal microbiota into normal individuals. The distribution ratio of intestinal microorganisms showed that Bacteroides and Firmicutes are as dominant phyla in the microbiota of all groups. Our result also revealed that hot water and ethanolic extracts of Padina pavonica and Cystoseira myrica were effective in changing intestinal microorganisms in obese rats. However, we found that all the extracts prepared from Cystoseira myrica were more efficient in diminishing the relative abundance of obesity-associated genera and increasing the leanness-associated genera in the treatment group compared with the control obese group. Clostridium and Lactobacillus were the dominant genera in all groups with pathogenic and lactic acid potentials. However, the anti-pathogenic effects of all Cystoseira myrica extracts were more effective than all Padina pavonica extracts.  Moreover, we also indicated that the extracts, especially those from hot water extracts of Padina pavonica and Cystoseira myrica were more effective in decreasing cholesterol, IL1 and TNF-α as well as liver enzymes such as ALP and AST in all treated groups.

Our findings supported that Cystoseira myrica could be a good choice for weight loss. The present study demonstrated that all the extracts could promote the growth of specific beneficial microbial populations, and reduce the abundance of both pathogenic bacteria and obesity-associated microbes. Furthermore, we showed that weight loss happened due to a decrease in food intake. Although, all the extracts from Padina pavonica and Cystoseira myrica resulted in lower level of cholesterol, inflammatory factors as well as liver enzymes, Cystoseira myrica was more effective than Padina pavonica. The best extract that could normalize all criteria was Cystoseira myrica. It seems that in vivo animal studies can be extended to humans as well, and therefore, we suggest that Cystoseira myrica may be used as a prebiotic material, with anti-obesity effects on human health.; however, it needs more investigation.