Intestinal Microbiome In Obesity
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Grzegorz W Telega |
| Children’s Hospital Of Wisconsin Since 2000 Program director, Liver Transplant Hepatology, Children’s Hospital of Wisconsin |
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The human microbiome, a complex community of microorganisms colonizing gastrointestinal system, has emerged as a significant player in metabolism and weight regulation. This chapter reviews current evidence regarding the relationship between the microbiome and obesity, emphasizing mechanisms of action, potential therapeutic targets, and implications for future research.
Introduction
The gut microbiome has emerged as a critical component development of obesity (Ley et al., 2006). The microbiome refers to the trillions of microorganisms, including bacteria, viruses, fungi, and archaea, that inhabit the human body, with the majority residing in the gut (Turnbaugh et al., 2006).
The Gut Microbiome
The gut microbiome plays essential roles in digestion, immunity, and the synthesis of certain vitamins (Tremaroli & Bäckhed, 2012). It is shaped by a variety of factors, including diet, age, geographic location, and lifestyle factors (Shreiner et al., 2015). The composition of the gut microbiome can influence metabolic processes, impacting energy extraction from food and the balance of lipid metabolism.
Numerous studies have identified key microbial taxa associated with obesity. For instance, the phyla Firmicutes and Bacteroidetes are predominant in the human gut. Research has shown that individuals with obesity tend to exhibit a higher ratio of Firmicutes to Bacteroidetes, potentially facilitating increased energy absorption from the diet (Ley et al., 2006).
Mechanisms Linking the Microbiome to Obesity
- Energy Harvesting
Microbes in the gut can break down complex carbohydrates that human enzymes cannot digest, leading to short-chain fatty acid (SCFA) production. SCFAs, such as acetate, propionate, and butyrate, serve as energy sources and have been implicated in fat storage and appetite regulation (Koh et al., 2016). SCFAs can regulate hormones like GLP-1 and PYY, promoting satiety (Blaut et al., 2018).
- Inflammation
Obesity is often associated with a state of low-grade chronic inflammation. The gut microbiome influences the immune system and the production of pro-inflammatory cytokines. Dysbiosis, an imbalance in microbiome composition, can lead to increased intestinal permeability, allowing bacterial components like lipopolysaccharides (LPS) to enter the bloodstream and trigger systemic inflammation (Cani et al., 2007). This inflammation contributes to insulin resistance, a hallmark of metabolic syndrome.
- Modulation of Hormonal Regulation
The gut microbiome also plays a role in the regulation of hormones related to appetite and metabolism. For example, certain gut bacteria can influence the secretion of hormones such as leptin and ghrelin, which regulate hunger and satiety (Cani et al., 2009). Additionally, microbial metabolites can affect the hypothalamus, impacting hunger signals.
- Interactions with Diet
Dietary components can significantly influence the microbiome composition. High-fat and high-sugar diets are associated with dysbiosis and an increase in Firmicutes, while a fiber-rich diet promotes a more diverse and healthy microbiome (De Filippo et al., 2010). Thus, dietary changes can lead to alterations in microbiome composition and, consequently, improve metabolic outcomes.
Obesity-Related Complications and the Microbiome
The consequences of obesity extend beyond weight gain and comprise a wide range of metabolic disturbances. Understanding the microbiome’s role in these complications hinges on recognizing how it contributes to pathophysiological processes.
- Type 2 Diabetes Mellitus (T2DM)
T2DM is closely linked to obesity and characterized by insulin resistance and impaired insulin secretion. The gut microbiome may influence the development of insulin resistance through inflammatory pathways and SCFA production. Disruptions in microbial composition can lead to increased levels of circulating LPS, promoting systemic inflammation and insulin resistance (Cani et al., 2008).
A study by Sato et al. (2021) found that a distinct microbiome composition was associated with improved glycemic control in obese individuals. This suggests that therapeutic modulation of the gut microbiome may offer avenues for T2DM management.
- Cardiovascular Disease (CVD)
Obesity is a major risk factor for cardiovascular disease, contributing to hypertension, dyslipidemia, and atherosclerosis. The microbiome has been implicated in cardiovascular health through its role in lipid metabolism. Certain gut bacteria can metabolize dietary fats, producing metabolites that may influence atherosclerosis development (Sustainable et al., 2015).
In addition, inflammatory processes driven by dysbiosis contribute to endothelial dysfunction and cardiovascular risk (Tang et al., 2019). Thus, modulating the gut microbiome may have protective effects against CVD.
Non-Alcoholic Fatty Liver Disease (NAFLD)
NAFLD, associated with obesity and insulin resistance, is increasingly recognized as a global health issue. The microbiome influences liver health through the gut-liver axis. Microbial metabolites such as SCFAs can affect liver metabolism, and dysbiosis has been linked to increased fat accumulation in the liver (Boursier et al., 2016).
Moreover, LPS derived from altered gut microbiota can induce hepatic inflammation, further exacerbating NAFLD (Zhang et al., 2019).
- Gastrointestinal Disorders
Obesity is frequently associated with gastrointestinal disorders such as gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). The gut microbiome’s role in digestion and inflammation may contribute to the manifestation of these disorders. Alterations in microbial diversity have been observed in patients with GERD, indicating a potential relationship between obesity and gastrointestinal health (El-Serag et al., 2014).
Therapeutic Implications
The recognition of the microbiome’s role in obesity has sparked interest in potential therapeutic interventions aimed at reshaping the gut microbial community.
- Probiotics and Prebiotics
Probiotics, live microorganisms that confer health benefits, and prebiotics, dietary fibers that promote the growth of beneficial bacteria, have been explored as strategies for obesity management. Certain strains of probiotics have shown promise in influencing body weight and composition (Kelley et al., 2016). Additionally, prebiotics can alter the gut microbiome composition, resulting in enhanced metabolic health (Slavin, 2013).
- Fecal Microbiota Transplantation (FMT)
FMT involves transferring fecal material from a healthy donor to a recipient to restore microbial balance. Preliminary studies have shown that FMT can aid in weight loss and improve metabolic parameters in obese patients (Kootte et al., 2017). However, safety concerns and variability in individual responses necessitate further research in this area.
- Dietary Interventions
Dietary modifications remain the cornerstone of obesity treatment. Emphasizing a diet rich in fiber, fruits, vegetables, and whole grains can promote a diverse and balanced gut microbiome. Plant-based diets have been associated with favorable shifts in microbial composition, leading to improved metabolic health (Wang et al., 2019).
Conclusion
The gut microbiome emerges as a pivotal player in obesity and its related complications, influencing metabolic pathways and inflammatory processes. Understanding this relationship could pave the way for innovative approaches to obesity management, underscoring the need for further research into microbiome modulation as a therapeutic strategy. Given the rising prevalence of obesity and its associated health burdens, prioritizing studies in this domain is crucial for developing successful interventions and improving public health outcomes.
References
– Blaut, M., et al. (2018). “The role of gut microbiota in the metabolism of dietary fiber.” *The Journal of Nutrition*.
– Boursier, J., et al. (2016). “The role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease.” *Cellular and Molecular Gastroenterology and Hepatology*.
– Cani, P. D., et al. (2007). “Changes in gut microbiota control metabolic endotoxemia-induced inflammation in obesity.” *Diabetes*.
– Cani, P. D., et al. (2008). “Involvement of gut microflora in the development of obesity.” *Current Diabetes Reports*.
– Cani, P. D., et al. (2009). “Gut microflora as a new key player in obesity.” *Diabetologia*.
– De Filippo, C., et al. (2010). “Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa.” *Proceedings of the National Academy of Sciences*.
– El-Serag, H. B., et al. (2014). “The relationship between obesity and gastroesophageal reflux disease.” *Gastroenterology*.
– Flegal, K. M., et al. (2012). “Prevalence of obesity in the United States.” *Journal of the American Medical Association*.
– Kelley, A. S., et al. (2016). “The probiotic Lactobacillus reuteri mitigates obesity-induced metabolic disturbances.” *Infection and Immunity*.
– Koh, A., et al. (2016). “From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites.” *Cell Metabolism*.
– Kootte, R. S., et al. (2017). “The efficacy of fecal microbiota transplantation in the treatment of obesity.” *The American Journal of Clinical Nutrition*.
– Ley, R. E., et al. (2006). “Obesity alters gut microbial ecology.” *Proceedings of the National Academy of Sciences*.
– Sato, T., et al. (2021). “Changes in the gut microbiome and their impact on glycemic control in people with obesity.” *Nature Communications*.
– Shreiner, A. B., et al. (2015). “The microbiome in health and disease.” *Annual Review of Pathology: Mechanisms of Disease*.
– Slavin, J. (2013). “Fiber and prebiotics: mechanisms and health benefits.” *Nutrients*.
– Sustainable, P. J., et al. (2015). “Gut microbiota and cardiovascular disease.” *Cardiovascular Research*.
– Tang, W. H. W., et al. (2019). “Intestinal microbiota in cardiovascular disease.” *Nature Reviews Cardiology*.
– Tremaroli, V., & Bäckhed, F. (2012). “Functional interactions between the gut microbiota and host metabolism.” *Nature*.
– Turnbaugh, P. J., et al. (2006). “An obesity-associated gut microbiome with increased capacity for energy harvest.” *Nature*.
– Wang, Y., et al. (2019). “Dietary patterns and gut microbiota in obesity.” *Nature Reviews Gastroenterology & Hepatology*.
– Zhang, H., et al. (2019). “Gut microbiome and its role in liver diseases.” *Nature Reviews Gastroenterology & Hepatology*.
