Page 33 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology Gut microbiome effects on obesity

To highlight CLA’s potential role in regulating 4.4. Trimethylamine N-oxide (TMAO)
interactions between the GM, host metabolism, and TMAO is a compound belonging to the amine oxides class,
immunity in attenuating insulin resistance, a study chemically represented as (CH ) NO. TMAO is produced
evaluated its effects in a mouse model of insulin resistance through the metabolism of dietary choline, L-carnitine, and
3 3
induced by a HFD. CLA supplementation improved betaine by the intestinal microbiota. 184,185 Specifically, it is
hyperglycemia, hyperlipidemia, glucose intolerance, and derived from the oxidation of trimethylamine (TMA). 186-188
insulin resistance. It enhanced antioxidant capacity and Moreover, the differentially expressed microbial genes
reduced fat deposits and inflammation in adipose tissue. summarized in the Kyoto Encyclopedia of Genes and
It also promotes fatty acid oxidation and insulin signaling Genomes Orthology (KO) suggest that these genes are
pathways. In addition, transcriptomic analysis revealed responsible for encoding the trimethyl N-oxide reductase
178
that CLA inhibited inflammatory signaling pathways while enzyme, which plays a crucial role in the conversion of
activating several beneficial metabolic pathways, including TMAO to TMA. 189
phosphoinositide 3-kinase-Akt, AMPK, and insulin-
related pathways. It also regulated specific metabolic TMAO levels increased in tandem with BMI, displaying
processes, such as those related to arachidonic acid, linoleic a positive association with both fatty liver index and visceral
190
acid, arginine, and proline metabolism. In the same mice adiposity index. A recent study revealed persuasive
model, CLA supplementation effectively reduced weight results regarding the relationship between TMAO levels
gain, adipose tissue weight, and adipocyte size compared and obesity, identifying that individuals in the highest
to HFD-fed mice without supplementation. 178 TMAO category exhibited an increase of 0.56 kg/m in
2
BMI. Furthermore, a dose-dependent association was
4.3. Bile acids metabolites observed between circulating TMAO levels and obesity
Bile acids are metabolites derived from cholesterol in the in individuals categorized as apparently healthy. Notably,
liver and subsequently metabolized by gut bacteria in the this study represents the first meta-analysis to unveil
intestines. The decrease of both primary and secondary these positive dose-dependent associations between
191
bile acid subtypes after the consumption of low-calorie the concentration of circulating TMAO and obesity.
weight-loss diets has shown a prominent correlation In addition, patients with obesity and colorectal cancer
with improving adiposity, fat accumulation, and energy display distinct GM characteristics, including a reduced
metabolism. This suggests that specific subtypes of bile abundance of butyrate-producing bacteria, accompanied
acids could serve as potential biomarkers for predicting by increased TMAO levels, increased pro-inflammatory
long-term weight-loss success and an individual’s cytokine IL-1β, and enhanced intestinal permeability. 192
response to dietary interventions. The GM assists in On the other hand, there are viable solutions to
179
bile acid metabolism by facilitating deconjugation and modulate TMAO levels. The Mediterranean diet, a high-
dehydroxylation processes inside the intestinal lumen. fiber diet, and probiotics have demonstrated their ability
These mechanisms convert primary bile acids into to reduce the effects of TMAO. A high-fiber diet led to
193
secondary bile acids, such as cholate into deoxycholate an increase in the abundance of beneficial bacteria such
and chenodeoxycholate into lithocholate. 180,181 This as Lactobacillus, Akkermansia, and Bifidobacterium while
process is promoted by bile salt hydrolase enzymes, which reducing the opportunistic pathogenic bacteria such as
mainly found in Firmicutes and Bacteroidetes, notably in Desulfovibrio and Klebsiella. 104
Clostridium genera clusters. 182

After analyzing the postprandial responses of bile 5. Bacteria taxa implicated in the control of
acids, the bile acid synthesis marker C4, fibroblast growth BW
factor 19 (FGF19), and farnesoid X receptor (FXR)- Evidence from various studies consistently demonstrates
regulated FGF19 in obese patients before and after surgery, that certain gut bacteria significantly influence
researchers observed a significant increase in total plasma obesity-related metrics, metabolic parameters, and fat
bile acid levels, while fecal excretion of these molecules accumulation by impacting intestinal health. The following
decreased. Furthermore, FGF19 levels increased, whereas table summarizes intestinal bacteria associated with
C4 levels decreased, indicating enhanced FXR activity in obesity based on studies conducted on mice and humans of
the gut. The increase in bile acid levels and the activation of different ages and weights. Table 1 compiles results derived
FXR may contribute to the observed metabolic benefits. 183 from several studies, highlighting the role of various GMs
Understanding the role of these bacterial metabolites in in BW regulation. Each bacterium’s specific influence is
weight loss remains an active area of research. examined individually.

Volume 9 Issue 2 (2025) 25 doi: 10.36922/ejmo.8318