foods Review Characteristics of the Gut Microbiota and Potential Effects of Probiotic Supplements in Individuals with Type 2 Diabetes mellitus Rafael Ballan 1,2 and Susana Marta Isay Saad 1,2, *   Citation: Ballan, R.; Saad, S.M.I. Characteristics of the Gut Microbiota and Potential Effects of Probiotic Supplements in Individuals with Type 2 Diabetes mellitus. Foods 2021, 10, 2528. https://doi.org/10.3390/ foods10112528 Academic Editors: Ana Gomes and José Carlos Andrade Received: 10 September 2021 Accepted: 19 October 2021 Published: 21 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000, SP, Brazil; Rafael.maluhy@gmail.com 2 Food Research Center, University of São Paulo, São Paulo 05508-080, SP, Brazil * Correspondence: susaad@usp.br; Tel.: +55-11-3091-2378 Abstract: The increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide has become a burden to healthcare systems. In 2019, around 463 million adults were living with diabetes mellitus, and T2DM accounted for 90 to 95% of cases. The relationship between the gut microbiota and T2DM has been explored with the advent of metagenomic techniques. Genome-wide association studies evaluating the microbiota of these individuals have pointed to taxonomic, functional, and microbial metabolite imbalances and represent a potential intervention in T2DM management. Several microbial metabolites and components, such as imidazole propionate, trimethylamine, and lipopolysaccharides, appear to impair insulin signaling, while short-chain fatty acids, secondary bile acids, and tryptophan metabolites may improve it. In addition, the use of probiotics with the aim of transiently restoring the microbial balance or reducing the effects of microbial metabolites that impair insulin sensitivity has been explored. Herein, we critically review the available literature on the changes in the gut microbiota in T2DM together with potential adjuvant therapies that may improve the health status of this population. Keywords: diabetes mellitus type 2; gut microbiota; microbial metabolites; dysbiosis; probiotics 1. Introduction Diabetes mellitus (DM) describes a group of metabolic disorders and is mainly charac- terized by chronic hyperglycemia resulting from impaired insulin secretion or impaired insulin action or both mechanisms together, causing long-term complications [1]. Persis- tent hyperglycemia is associated with chronic micro and macrovascular complications. People with diabetes are at an increased risk of developing numerous health problems that may be life threatening, such as vascular damage that affects the heart, eyes, kidneys, and nerves [2]. Clinical presentation and the progression of type 1 and type 2 diabetes usually vary considerably due to the distinct pathophysiology of the diseases. An early accurate classification is important for determining therapy although this is sometimes is not possible [3]. Type 2 diabetes (T2DM), which accounts for 90 to 95% of all DM cases, is the most common metabolic disorder and is characterized by insulin resistance and pancreatic β-cell dysfunction, which lead to unstable hyperglycemia [4,5]. In the case of β-cell dysfunction, insulin secretion is decreased, limiting the body’s ability to maintain physiological plasma glucose levels, whereas insulin resistance contributes to increased glucose production in the liver and decreased glucose uptake in the muscle, adipose tissue, and liver [6]. It has a complex and multifactorial etiology that involves genetic and environmental components and usually affects individuals from the fourth decade of life, although there has been an increase of the incidence of diabetes in children and young people. The risk factors for T2DM are genetic susceptibility, age, obesity, physical inactivity, previous diagnosis of pre-diabetes or gestational diabetes (DMG), inadequate diet, and stress [2,7]. Foods 2021, 10, 2528. https://doi.org/10.3390/foods10112528 https://www.mdpi.com/journal/foods