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Microbes & Immunity Management of obesity

between primary and secondary bile acids. 20,21 Research immune balance, gut health, and metabolic stability,
indicates that gut microbiome deficiency can modulate making them essential for overall wellbeing. 24
cytochrome P450 family 7 subfamily A member 1
expression, alleviating HFD-induced metabolic syndrome, 6. Mechanisms of impact of gut microbiota
and thus represents a potential therapeutic target for on obesity
obesity. Experimental treatments further demonstrate the The human gut microbiome, composed of trillions
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significance of bile acid modulation in metabolic health. In of bacteria, plays a crucial role in digestion, immune
obese mice, colesevelam (a bile acid sequestrant) enhanced function, and brain activity. Recent studies challenge
GLP-1 secretion and improved glucose levels through FXR- the traditional belief that obesity results solely from
dependent mechanisms, suggesting potential for type 2 excessive calorie intake, highlighting the significant role
diabetes treatment. In addition, antibiotic interventions of the gut microbiota in metabolic disorders that lead to
have been shown to suppress FXR signaling, improving weight gain. Certain bacterial species, such as Firmicutes,
glucose tolerance and reducing hepatic steatosis. Dietary enhance energy extraction from food by fermenting
interventions also influence bile acid metabolism. A high- complex carbohydrates into SCFAs, which regulate
protein diet increased the abundance of Eubacterium species, metabolism, satiety, and energy expenditure through
which metabolize bile acids through 7α-dehydroxylation, interactions with gut hormones. Microbial metabolites,
resulting in elevated deoxycholic acid and lithocholic acid including bile acids and SCFAs, influence lipid absorption,
levels. Specific dietary modifications appear beneficial for glucose balance, and thermogenesis. Disruptions in the
metabolic regulation and obesity prevention. Methionine gut microbiota can impair intestinal barrier integrity,
restriction stabilizes lipid profiles in HFD-induced allowing harmful LPS to enter circulation and triggering
metabolic disorders, while extruded legumes and cereals inflammation and metabolic dysfunction. Furthermore,
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enhance bile acid excretion, promoting lipid homeostasis. the gut–brain axis plays a vital role in appetite regulation,
Notably, common buckwheat supplementation has shown with gut bacteria producing neurotransmitters, such as
promise in preventing NAFLD and dyslipidemia by gamma-aminobutyric acid (GABA) and serotonin, which
regulating primary bile acid biosynthesis and modulating influence feeding behavior and mood. Dietary choices
gut microbiome composition. Overall, secondary bile significantly impact the gut microbiota; diets rich in
acids play an integral role in metabolic regulation, with saturated fats and low in fiber promote pro-inflammatory
potential therapeutic applications through dietary and bacteria, contributing to insulin resistance, fat storage,
pharmacological interventions. 22 and adipose tissue inflammation – key features of obesity.
Understanding these mechanisms has opened new
5.2. Taurine, ATP, and polysaccharide A (PSA) possibilities for microbiota-based interventions to improve
Several key metabolites, including taurine, ATP, and PSA, metabolic health and address obesity. 25
play pivotal roles in immune regulation within the gut. ATP,
secreted by certain intestinal bacteria, interacts with P2X 7. Energy homeostasis disruption
and P2Y receptors, amplifying T cell receptor signaling, The fate of energy extracted by the gut microbiota
promoting inflammatory responses in macrophages and from dietary components that escape digestion and
DCs, and influencing immune activation. It binds to absorption in the small intestine represents a fundamental
seven P2X receptors (P2X1R–P2X7R) and eight GPCRs bioenergetic principle linking diet, microbial activity,
(P2Y1R–P2Y14R), leading to ion exchange and cellular and the energy ultimately available to the human host.
immune modulation. Taurine, an essential amino acid This energy, derived from microbial fermentation, is
found abundantly in immune cells, supports intestinal predominantly generated from carbohydrates in the host’s
microbial metabolism, enhances T cell proliferation, diet and, to a lesser extent, from proteins. Approximately
stimulates SCFA production, and reduces LPS levels, 90% of the caloric intake from a meal is absorbed in the
thereby contributing to gut homeostasis. PSA, produced small intestine, with absorption rates ranging between
by gut bacteria, plays a protective role by activating TLR2 83% and 97%. 26,27 Upon reaching the colon, undigested
on DCs, stimulating IL-10 secretion by T cells, and directly dietary components undergo microbial fermentation,
binding to TLR2 on forkhead box P3-positive regulatory producing energy that is either absorbed by the host,
T cells, further increasing IL-10 production to regulate utilized for microbial biomass growth, or excreted in feces.
inflammation. PSA has also been shown to counteract The energy absorbed by the host is typically estimated as
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gut inflammation by suppressing mucosal effector T cell a percentage of consumed energy, after deducting energy
(T helper 17 cell) activity, thereby mitigating conditions, lost in a feces that is not fully utilized by either the host or
such as colitis. Together, these metabolites help maintain the microbiota; this is referred to as metabolizable energy.
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Volume 2 Issue 4 (2025) 44 doi: 10.36922/MI025160036