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Adjuvant therapeutic interventions to alleviate Adiposity / Obesity and associated comorbidities are traditionally based on diet modulation and the supplementation of prebiotics, probiotics, and synbiotics
(brain://A19tpNsir0mVRstg3H-ePA/BaroneEtAl2021aWorldJGastroenterol274170417064)
These approaches have shown only moderate ability to induce sustained changes in the gut microbial ecosystem
The Microbiota of People with Adiposity / Obesity Has an Increased Ability to Get Food Energy from Their Diet
Anaerobic Bacteria Can Inhibit Adiposity / Obesity
The gut microbiota profile of patients with overweight and adiposity / obesity with dyslipidemia in Xinjiang was characterized by enrichment of Lactobacillus and the reduction of the diversity and the depletion of Actinobacteria, Bacteroides, Bifidobacterium, and Bacteroides fragilis
The contribution of the gut microbiota to adiposity / obesity was highly dependent on geography and dietary habits
Obesity is one of the main features of metabolic syndrome , in which low-grade chronic inflammation and intestinal dysbiosis contribute to the development of associated metabolic disorders .
↓ or ↑ : reduced or increased abundance in obesity compared to normal-weight individuals
Overall, individuals with obesity exhibit lower microbial richness and diversity, as well as a reduced microbial gene count, compared to those of normal weight. Numerous studies have identified specific microbial species, along with their metabolic and functional characteristics, as being associated with obesity. However, the findings often vary between different studies.
The following list highlights common patterns observed across various studies, though it is not exhaustive in terms of all altered taxonomic, metabolite, and functional characteristics:
These patterns provide insight into the complex relationship between the microbiome and obesity, despite the variability in study results.
Animals fed a high-fat diet, and orally fed Clostridia were protected from diet-induced obesity and metabolic syndrome.
Klag & Round 2021 J Immunol 207: 1719-1724
Animal researches support the connection between Adiposity / Obesity & Firmicutes / Bacillota and the increase of gastrointestinal bacteria from phyla Firmicutes and Bacteroidetes .
Animal studies also confirm that gastrointestinal bacteria regulate blood lipid levels in human organisms
Diet-derived metabolites regulate thermogenesis and thus energy homeostasis .
The majority of meta-analyses of human studies on the association between antibiotics and subsequent development of obesity suggest a link between exposure to antibiotics, particularly early exposure in life, and the development of subsequent obesity as a result of alterations in the diversity of gut microbiota.
The evidence is strong in animal models, whereas evidence in humans is inconclusive.
Based on recent meta-analyses and epidemiologic studies in healthy children, factors, such as the administration of antibiotics during the first 6 months of life, repeated exposure to antibiotics for ≥ 3 courses, treatment with broad-spectrum antibiotics, and male gender have been associated with increased odds of overweight/obesity.
Early antibiotic exposure in animal models has shown that reductions in the population size of specific microbiota, such as Lactobacillus, Allobaculum, Rikenellaceae, and Candidatus Arthromitus, are related to subsequent adiposity.
Further well-designed, large-scale RCTs in humans are required to evaluate the effects of administration of antibiotics, particularly early administration, and the subsequent development of overweight/obesity addition.
In obesity, the adipose tissue is infiltrated with inflammatory immune cells that produce high pro-inflammatory cytokines and chemokines.
In addition, the gut barrier is disrupted, causing gut antigens and PAMPs such as LPS to enter the tissue and stimulate inflammation.
A distorted gut immunity leading to an inflammatory state is likely an early trigger for obesity and its comorbidities (e.g., type 2 diabetes, fatty liver disease).
Global changes caused by urbanisation, loss of biodiversity, industrialisation, and land-use are happening alongside microbiota dysbiosis and increasing adiposity / obesity prevalence
Bile acids synthesized by gastrointestinal bacteria move from the intestine into the bloodstream and modulate the hepatic and system metabolism of lipids and glucose
Interventions targeting the modulation of gut microbiota and its metabolites are effective for adiposity / obesity and its comorbidities
Microbial metabolites such as bile acids , SCFAs , mainly butyrate , acetate and Propionate / Propionic acid , branched chain amino acids (BCAAs ), aromatic amino acids , and trimethyl-amin-N-oxide (TMAO ), play a pivotal role in the metabolic pathways implicated in obesity
Among the gut microbial metabolites, we emphasize short-chain fatty acids , which could be utilized by the host as a direct energy source while regulating the appetite of the host through the gut-brain axis
In a healthy state, commensal microbes show reduced levels of pathogen-associated molecular patterns (PAMP).
However,
Constant dietary inflammatory burdens from Refined sugars and saturated fatty acids have profound effects on the gut microbiota, impair the gut barrier function, and intestinal immunity
Zhou et al. 2020 J Inflamm Res 13: 1-14
Animal studies showed that obesity was associated with a loss of diversity, particularly within the class Clostridia, and with enrichment in the genus Desulfovibrio
In a recent animal study, Konopelski et al. found that a tryptophan -rich diet reduced weight gain in rats compared with a control group via an increase in production of gut bacteria-derived indole propionic acid from tryptophan
The concentrations of aromatic amino acid-derived microbial metabolites , including benzoic acid (BA), phenylacetic acid (PAA), Phenylpropionic acid (PPA) ), p-Hydroxybenzoic acid (p-HBA) ), p-Hydroxyphenylacetic acid (p-HPAA) ), 3,4-Dihydroxyphenylacetic acid (DOPA), indoleacetic acid (IAA), indole propionic acid (IPA), and 5-Hydroxyindoleacetic acid (5-HIAA) ), which are produced through deamination , transamination , decarboxylation , and dehydrogenation reactions, are altered in metabolic disorders
A high-fat diet leads to structural instability among the gut microbiota, further increasing endotoxins , which aggravates obesity
Dietary Lipids are transported through the intestinal wall, passing through the gastrointestinal mucosa and binding to bad lipoproteins .
Diets rich in coconut oil ≥25% administrated to healthy female animal models for 8 or 10 weeks showed adiposity/obesity and its related dysfunction effects and increase of Allobaculum , Clostridium , Lactobacillus , Staphylococcus , and the Firmicutes to Bacteroidetes ratio in their guts
Org et al. and Piening et al. also showed higher serum and plasma levels of BCAAs and phenylalanine in obese subjects and individuals with high insulin resistance values. BondiaPons et al. revealed that plasma BCAAs were increased in heavier twins compared with leaner co-twins in the fasting state
The gut microbiota of obese individuals may have a higher capacity for production of aromatic amino acids and branched-chain amino acids (BCAAs ) in comparison with lean controls
The aromatic amino acids were negatively correlated with Bacteroides species, including B. thetaiotaomicron , B. intestinalis , B. ovatus , and B. uniformis, and Christensenellaceae
In adiposity/obesity, it’s widely believed that gut microbiota can increase energy harvest from diet and contribute to low-grade inflammation, leading to the development of adiposity / obesity
The decrease in short-chain fatty acids (SCFA) producing bacteria indicates a disorder of glucose homeostasis
Metagenomic analysis of the gut microbiome in obese mice and humans indicated that expression of genes involved in carbohydrate metabolism predominated
Metabolic endotoxemia is a form of systemic inflammation in which bacteria appear to mediate the risk of metabolic disease
In overweight adults, the gut microbiota changes toward a less beneficial composition, and this change may be accompanied by inflammation.
Importantly, microbiota transplanted from obese mice or humans into Germ-free Mice (GF Mice) / Germ-free Animal results in significantly more significant weight gain when compared with mice that received microbiota from a lean individual
Additionally, Germ-free Mice (GF Mice) / Germ-free Animal gain significantly less weight on a high-fat diet
ATPase complex and ectoine biosynthesis correlate significantly with Body Mass Index
Xanthine has been shown to decrease in obese individuals. Moreover, a decreased urinary level of xanthine was associated with an increased serum level of uric acid in obese subjects
Indeed, obesity is thought to be an inflammatory state characterized by a positive correlation between fat mass and the expression of TNF-alfa and other pro-inflammatory cytokines
Transplantation of the microbiota from mice with DIO to lean germ-free recipients produced a significantly greater increase in adiposity than transplants from lean donors
Changes in the gut microbiota structure (Dysbiosis) may reduce AMPK in the liver and muscle and thereby inhibit AMPK-dependent fatty acid oxidation , which can lead to fat accumulation
Gut Microbiota Is an Additional Contributing Factor to the Pathophysiology of Adiposity / Obesity
Colonization of Germ-free Mice with an ‘obese Microbiota’ Results in a Significantly Greater Increase in Total Body Fat than Colonization with a ‘lean Microbiota’
A significantly increased ratio of Firmicutes/Bacteroidetes was characteristic of individuals with Adiposity / Obesity
The gut microbiota plays a vital role in developing obesity as microbes can harvest energy from indigestible dietary substances
However, differences in gut microbial ecology between humans may be an important factor affecting energy homeostasis
For example, individuals predisposed to obesity may have gut microbial communities that promote more efficient extraction and or storage of Food Energy from a given diet than those in lean individuals.
Further, when obese volunteers followed a weight-loss diet for months, there was a significant increase in Bacteroides, but not equal to lean individuals
The urinary concentration of the indolic compound 5-HIAA , a clinical indicator of gastrointestinal carcinoid tumors, was elevated in obesity by the monoamine oxidase activity of Escherichia coli
Intestinal microflora SCFAs have been reported to benefit host metabolism and appetite
In response to feeding a high-fat diet to rat models, metabolism and elimination of p-HPAA , a metabolite produced from tyrosine by gut microbiota , altered in such a way that the p-HPAA concentration decreased in urine while it increased in serum and feces. p-HPAA can be further metabolized to p-cresol through decarboxylation by Clostridium difficile . These alterations suggest the underlying mechanisms of accumulation of p-cresol and overgrowth of C. difficile in obesity
Mechanistically, evidence supporting the importance of Myo-inositol / Inositol in obesity has recently been found.
A Megamonas-dominated enterotype-like cluster is positively associated with obesity.
Megamonas rupellensis possessed genes for the degradation of myo-inositol. The addition of Myo-inositol effectively inhibited fatty acid absorption in intestinal organoids.
Furthermore, mice colonized with M. rupellensis or E. coli heterologously expressing the myo-inositol-degrading iolG gene showed increased intestinal lipid absorption, leading to obesity.
see also:
Adiposity / Obesity & Dysbiosis
Adiposity / Obesity & Short-Chain Fatty Acids (SCFAs)
Adiposity / Obesity & Western Diet (WD) / Western Pattern Diet
Dietary Fibers (DF) & Adiposity / Obesity