Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications

Abstract

Diverse evidence suggests that the gut microbiota is involved in the development of obesity and associated comorbidities. It has been reported that the composition of the gut microbiota differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. However, the mechanisms by which the gut microbiota participates in energy homeostasis are unclear. Gut microbiota can be modulated positively or negatively by different lifestyle and dietary factors. Interestingly, complex interactions between genetic background, gut microbiota, and diet have also been reported concerning the risk of developing obesity and metabolic syndrome features. Moreover, microbial metabolites can induce epigenetic modifications (i.e., changes in DNA methylation and micro-RNA expression), with potential implications for health status and susceptibility to obesity. Also, microbial products, such as short-chain fatty acids or membrane proteins, may affect host metabolism by regulating appetite, lipogenesis, gluconeogenesis, inflammation, and other functions. Metabolomic approaches are being used to identify new postbiotics with biological activity in the host, allowing discovery of new targets and tools for incorporation into personalized therapies. This review summarizes the current understanding of the relations between the human gut microbiota and the onset and development of obesity. These scientific insights are paving the way to understanding the complex relation between obesity and microbiota. Among novel approaches, prebiotics, probiotics, postbiotics, and fecal microbiome transplantation could be useful to restore gut dysbiosis.

Interplay of an Obesity-Based Genetic Risk Score with Dietary and Endocrine Factors on Insulin Resistance

“…In addition, although the HOMA-IR index is a widely accepted indirect measurement of IR, the gold standard technique to assess this parameter could provide more information. Furthermore, interactions between the genetic makeup and other emerging factors affecting the host metabolism such as gut microbiota composition and epigenetic signatures also need to be explored [45].…”

Gut-Brain Axis: Probiotic,Bacillus subtilis, Prevents Aggression via the Modification of the Central Serotonergic System

“…Probiotics are commensal bacteria ("direct-fed microbials", DFM) that offer potential health beneficial bio-physiological effects to the host's stress response (acute, chronic, or both). Probiotics aid animals in adapting to their environments and protect against pathogens by: (1) altering the microbiota profile with beneficial bacteria to prevent the growth of pathogens and to compete with enteric pathogens for the limited availability of nutrient and attachment sites; (2) producing bacteriocins (such as bacteriostatic and bactericidal substances) and short-chain fatty acids against pathogens to regulate the activity of intestinal digestive enzymes and energy homeostasis and to increase mineral solubility; (3) reducing oxidative stress, inflammation, and acinar cell injury; (4) modulating host immune and inflammatory responses and restoring the intestinal barrier integrity which prevents pathogens from crossing the mucosal epithelium; (5) stimulating the endocrine system and attenuating stress-induced disorders of the HPA and/or SMA axes via the gut-brain axis; and (6) inducing epithelial heat shock proteins to protect cells from oxidative damage; and (7) synthesis and secretion of neurotransmitter such as 5-HT and tryptophan [16,17,[222][223][224][225][226]. In both human and rodent studies, probiotics reduce cognitive dysfunction, decrease the stress response and related oxidative damage by lowing plasma CORT and ACTH levels, restore hippocampal 5-HT levels, and normalize immunity with low plasma levels of TNF-α (tumor necrosis factor-α), a proinflammatory cytokine, but high levels of IL-10 (Interleukin-10), an anti-inflammatory cytokine [67, [227][228][229][230].…”

Circulating microbiota-derived metabolites: a “liquid biopsy?

“…This hypothesis considers multiple insults acting together, including hormones/adipokines secreted from the adipose tissue, lipotoxicity, oxidative stress, mitochondrial dysfunction, genetic and epigenetic factors, and gut microbiota [5]. The dysregulation of gut microbiota has been found to be involved in a variety of metabolic diseases, such as diabetes, insulin resistance, obesity, and NAFLD [6].…”