Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients

Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients Daniel A. Medina1 , Juan P. Pedreros1 , Dannae Turiel2 , Nicolas Quezada2 , Fernando Pimentel2 , Alex Escalona3 and Daniel Garrido1 1 Department of Chemical and Bioprocess Engineering, Pontificia Universidad Católica de Chile, Santiago, Chile 2 Department of Digestive Surgery, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile 3 Department of Surgery, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile ABSTRACT Submitted 24 February 2017 Accepted 18 May 2017 Published 20 June 2017 Corresponding author Daniel Garrido, Academic editor Jie Liu Additional Information and Declarations can be found on page 15 DOI 10.7717/peerj.3443 Copyright 2017 Medina et al. Distributed under Creative Commons CC-BY 4.0 Bariatric surgery is highly successful in improving health compared to conventional dietary treatments. It has been suggested that the gut microbiota is a relevant factor in weight loss after bariatric surgery. Considering that bariatric procedures cause different rearrangements of the digestive tract, they probably have different effects on the gut microbiota. In this study, we compared the impact of medical treatment, sleeve gastrectomy and Roux-en-Y gastric bypass on the gut microbiota from obese subjects. Anthropometric and clinical parameters were registered before, 6 and 12 months after treatment. Fecal samples were collected and microbiota composition was studied before and six months post treatment using 16S rRNA gene sequencing and qPCR. In comparison to dietary treatment, changes in intestinal microbiota were more pronounced in patients subjected to surgery, observing a bloom in Proteobacteria. Interestingly, Bacteroidetes abundance was largely different after six months of each surgical procedure. Furthermore, changes in weight and BMI, or glucose metabolism, correlated positively with changes in these two phyla in these surgical procedures. These results indicate that distinct surgical procedures alter the gut microbiota differently, and changes in gut microbiota might contribute to health improvement. This study contributes to our understanding of the impact of weight loss surgery on the gut microbiota, and could be used to replicate this effect using targeted therapies. Subjects Genomics, Microbiology, Gastroenterology and Hepatology, Surgery and Surgical Specialties Keywords Human gut microbiota, Gastric bypass, Sleeve gastrectomy, Bariatric surgery INTRODUCTION Obesity is a worldwide health problem that negatively affects quality of life. According to the World Health Organization (2016), more than 1,900 million people over 18 years old have a body mass index (BMI) of 25 kg/m2 or greater, and 600 million are catalogued as obese, with BMI ≥ 30 kg/m2 . Type 2 diabetes, cardiovascular disorders, certain cancers and asthma are comorbidities that show an increased risk in subjects with obesity. OPEN ACCESS How to cite this article Medina et al. (2017), Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients. PeerJ 5:e3443; DOI 10.7717/peerj.3443 The first line of treatment for obesity is medical treatment, which combines diet and physical activity. Unfortunately, the effectiveness of this approach appears to be only short term, since weight regain is common and not all patients respond similarly (Kral et al., 2012). In subjects with obesity and comorbidities, surgical procedures have been successful in controlling weight in the long term and reducing the incidence of related comorbidities, such as hypertension and type 2 diabetes (Sjöström et al., 2007; Sjöström, 2008; Eldar et al., 2011). These procedures are collectively known as bariatric surgery (BS). Indications for BS include a BMI more than 40 or a BMI more than 35 with medical comorbidities (Mechanick et al., 2013). BS can either restrict food intake (restrictive), or reduce nutrient absorption (malabsorptive) (Buchwald et al., 2004). Sleeve gastrectomy (SG) is an example of a restrictive procedure. It removes a significant portion of the stomach, decreasing its volume and leading to a significant reduction in the amount of food consumed (Gumbs et al., 2007). Meanwhile, Roux-en-Y gastric bypass (RYGB) is both restrictive and malabsorptive, creating a small stomach pouch connected to the proximal jejunum, reducing stomach volume to restrict food intake and bypassing food to the small intestine (Tice et al., 2008). Both procedures cause anatomical rearrangements that directly change gastrointestinal anatomy and function, accelerating food transit and altering hormonal regulation (Tice et al., 2008; Tran et al., 2016). While weight loss could be more pronounced in patients undergoing RYGB compared to SG after two years, the risk for post-surgical complications is greater in patients who have undergone RYGB (Lager et al., 2016). Other studies indicate that RYGB significantly outperforms SG in achieving glycated haemoglobin (HbA1C) values under 7.0% without medications (Schauer et al., 2014). In aggregate, these observations make interesting to understand the changes in the gut microbiota associated to both surgeries. The intestinal microbiota has been shown to have a strong impact on host health and is considered a metabolic organ. It consists of a dense community of microorganisms that matches the number of cells of the human body (Sender, Fuchs & Milo, 2016). The influence of the gut microbiota is better exemplified at the metabolic level, since the microbiota synthesizes vitamins and amino acids absorbed by the epithelium (LeBlanc et al., 2013). Additionally, it is capable of fermenting complex dietary polysaccharides and other dietary sources, resulting in the production of short chain fatty acids (SCFA) such as acetate, propionate and butyrate (Cook & Sellin, 1998; Hijova & Chmelarova, 2007; Morrison et al., 2016). These acids modulate physiological processes in several tissues, such as insulin sensitivity, liver function and cholesterol metabolism (Todesco et al., 1991; Demigné et al., 1995; Fushimi et al., 2006; Gao et al., 2009; Den Besten et al., 2013). Furthermore, the gut microbiota plays important roles in the development of the immune system and the maintenance of intestinal epithelium integrity (Sekirov et al., 2010). Certain studies have linked obesity with changes in the composition and metabolic function of the gut microbiota (Bäckhed et al., 2004; Ley et al., 2005; Turnbaugh et al., 2006; Tremaroli et al., 2015; Palleja et al., 2016). The gut microbiota is dominated by species that belong mainly to the Firmicutes and Bacteroidetes phylum, and to a lesser degree to Actinobacteria, Proteobacteria and Verrucomicrobia (Qin et al., 2010). In obese subjects, there has been an observed decrease in the relative proportion of the Bacteroidetes/Firmicutes Medina et al. (2017), PeerJ, DOI 10.7717/peerj.3443 2/22 ratio, comp (...truncated)