The Critical Role of Gut Microbiota and its Association with Obesity and Related Diseases View PDF

An overview of the obesity epidemic

A number of genetic and nongenetic factors (such as environmental factors) contribute to obesity. Depending on the country, the World Health Organization defines obesity as having a body mass index (BMI) above 30. An obese person in the USA, for example, has a BMI of 28 or higher. According to a comprehensive analysis, approximately onethird of the world’s population is overweight, and approximately 10% is obese. According to few other projections, 81% of Americans will be obese or overweight by 2030, while approximately 39% of children and 46% of adolescents will have abnormally high BMIs [1, 2]. The risk of adult obesity is increased by a meta-analysis of available data showing that half of obese children were still obese as adults; the risk is doubled if both parents are obese. Childhood obesity (defined as a BMI for age (or BMI-for-age) percentile greater than 95%) is a major risk factor for adult obesity. Several factors contribute to obesity’s etiology, including genetics, hormones, socioeconomics, and environmental factors [3]. It is also possible that comorbidities and their treatment might play a role in the prevalence and progression of obesity [4]. Obesity is caused by primary and secondary disease-related factors. Globally, there will be 1.12 billion obese people by 2030. There has been widespread concern about obesity’s health risks, and it has become a global health concern. It is not only associated with changes in appearance, but also with lipid and glucose metabolism disorders, chronic inflammation, oxidative stress, and an increased risk of several diseases, including cardiovascular disease, diabetes, and cancer [5]. Increasing evidence suggests that obesity may be caused by an imbalance in the gut microbiota.

There are about 100 trillion symbiotic microbes living in the gut, known as the gut microbiota, which is 10 times as many as the body’s own cells. To maintain its high population levels, the gut microbiota eats food residues that the human body doesn’t digest, secretes mucus, and sheds dead cells. As a result of gut microbiota activity, a wide range of physiologically active substances will be produced, including short-chain fatty acids, vitamins, anti-inflammatory, analgesic, and antioxidant products, as well as potentially harmful substances like neurotoxins, carcinogens, and immunotoxins. In addition to entering the bloodstream, these products directly regulate gene expression and affect the human immune system and metabolism [6, 7]. In order to maintain a healthy metabolism and an even energy balance, the gut microbiota must be in good health. Dysbiosis of the gut microbiota can lead to metabolic disorders as well as an increase in central appetite, resulting in obesity. Among the genetic syndromes associated with obesity are physical characteristics, such as dysmorphic features, developmental delays, and mental retardation. Genetic defects usually involve multiple genes and are often chromosomal abnormalities [8]. A common cause of obesity in children is Prader-Willi syndrome. There are many secondary causes of obesity, including systemic dysfunctions and disorders of regulatory mechanisms that cause metabolic changes in the body, leading to obesity secondary to primary illness. Homeostasis disruptions caused by diseases lead to the body’s inability to maintain energy balance, abnormal hormone synthesis, and altered consumption patterns. Maternal gestational weight gain has been linked to obesity in infancy, and maternal gestational weight gain is an independent predictor [9-11]. Genetics is strongly associated with obesity, meaning that multiple genes and their complex interactions can result in monogenic (5% of cases) or polygenic obesity. In addition to medical treatment, bariatric surgery can extend a person’s life expectancy. An overview of research into the relationship between obesity and gut microbiota is presented in this article [12].

We can influence our physiology in several ways through the body’s microbiome, which includes bacteria, viruses, archaea, and eukaryotic microbes. Researchers have shown that gut microbiome composition increases dietary energy intake, and therefore promotes obesity [13]. There are differences in the composition of microbial populations throughout the gastrointestinal tract. Because of the esophageal motility and the acidic unfavorable environment of the stomach, there are quantitatively few microorganisms, with most bacteria coming from the oral cavity [14]. There are already numerous bacteria in the intestinal microbiota, for example, Streptococcus is the most abundant in the Jejunum, while the ileocecal region is inhabited by bacteria from the phylum Firmicutes, primarily Streptococcaceae), bacteria from the phylum Actinobacteria (especially the subgroups Actinomycinaeae and Corynebacteriaceae), Bacteroidetes, and Lachnospiraceae. Due to the favorable pH for bacteria to colonize, the distal segment of the ileum and colon has the most bacteria and the greatest microbial diversity, as well as the fact that food content is retained longer in the intestinal lumen due to antiperistaltic contractions. Bacteroides and Clostridium are primarily Gram-positive bacteria, followed by Lactobacillus, Enterococcus, and Enterobacteriaceae [15]. Recently, several molecular pathways and some substances produced by the gut microbiota have been linked to obesity, suggesting a relation between gut microbiota imbalance and obesity. It is important to note that the correlations remain complex, so only a few will be discussed in the following sections. Based on the results discussed here, manipulation of the gut microbiota may be a potential treatment or prevention of obesity and its metabolic consequences [16].

A key factor inhibiting DNA damage repair mechanisms is obesity, which increases the risk of other associated diseases. An irreversible cell-cycle arrest can occur as a result of DNA damage, activation of adipocyte differentiation and hypertrophy proteins, disturbances in cell metabolism, impairments in glucose metabolism, and the development of insulin resistance in the system. BMI is correlated with insulin resistance, type 2 diabetes, and cardiovascular disease, which are wellestablished weight-related comorbidities. Additionally, obesity causes adverse health outcomes including sleep apnea, hypertension, heart disease, stroke, osteoarthritis, and certain types of cancer, as well as psychosocial problems like stigmatization and low self-esteem [17].

It is indisputable that obesity adversely affects cardiometabolic health; abdominal obesity is especially associated with cardiovascular disease, and it has been shown to disrupt adipocyte biology and adipose tissue inflammation, which have direct systemic metabolic consequences such as endothelial dysfunction and atherogenesis. A significant association has also been found between COVID-19 and obesity in multiple studies. There is an enhanced hospitalization rate, a more severe progression, and a worse outcome for COVID-19 patients with obesity. Urbanization is widely credited with contributing to the worldwide increase in BMI because diet and lifestyle in cities contribute to adiposity; however, a persistently higher rural BMI for women was observed in high-income and industrialized countries [18]. Obesity is associated with sedentary behavior and time spent watching television. There are several factors associated with a lower quality diet, including being male, living outside the university city, having a mother who is low socioeconomic status, and studying a health-related course. BMI and consumption of a high protein/fat Westernized diet were positively correlated. Researchers found that experimental reductions in sleep duration lower leptin levels, increase ghrelin levels, and increase appetite and hunger in adults [19-22].