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Microbes & Immunity Management of obesity

associated with anti-inflammatory effects and metabolic imidazole propionate and tryptophan derivatives, which
health. Similarly, studies across different populations have influence insulin resistance and metabolic syndrome.
noted variability in microbiota composition, suggesting Disrupted aryl hydrocarbon receptor (AhR) signaling,
that bacterial groups beyond the Firmicutes/Bacteroidetes caused by altered tryptophan metabolism, contributes
dichotomy influence obesity risk. Beyond compositional to obesity-related inflammation. Reduced AhR ligand
changes, gut microbiota-derived metabolites play a production diminishes IL-22 synthesis, exacerbating gut
major role in obesity. Short-chain fatty acids (SCFAs), permeability and metabolic dysfunction. Meanwhile,
including propionate, acetate, and butyrate, are produced microbial-derived components, such as flagellin and
through microbial fermentation of dietary fiber. These muramyl dipeptide show potential benefits in alleviating
compounds have dual effects on metabolism – they can diet-induced inflammation and insulin resistance.
increase satiety, enhance energy expenditure, and reduce
fat accumulation; however, excessive SCFA production 3. Metabolite production by gut microbiota
may also promote lipid synthesis, potentially contributing The gut microbiota secretes a variety of metabolites that
to obesity. In addition, secondary bile acids, another group influence host metabolism, immune responses, and overall
of microbial metabolites, help regulate lipid metabolism health. In obesity and metabolic disorders, dysbiosis
and gut hormone secretion, reinforcing their influence disrupts the balance of microbial metabolites, leading to
on energy balance. A key feature of obesity is chronic increased adiposity, inflammation, oxidative stress, and
low-grade inflammation, which is largely influenced by metabolic dysfunction. These metabolites originate from
the gut microbiota. Lipopolysaccharides (LPS), derived both dietary sources and endogenous compounds and
from Gram-negative bacteria, such as Bacteroidetes, include indole derivatives, SCFAs, polyamines (putrescine,
are major triggers for inflammation. These endotoxins spermidine, and spermine), secondary bile acids, and
compromise intestinal barrier integrity, allowing microbial adenosine triphosphate (ATP). SCFAs, produced by
byproducts to enter systemic circulation, which activates bacterial fermentation of dietary fiber, play crucial roles in
immune responses and disrupts metabolic disruption. immune signaling by activating receptors on neutrophils,
Elevated plasma LPS levels have been correlated with macrophages, and dendritic cells (DCs). This activation
increased fat deposition, insulin resistance, and heightened promotes the production of IL-18, IL-22, IgA, and the
inflammation, emphasizing the gut microbiota’s role in satiety hormone glucagon-like peptide-1 (GLP-1). SCFAs
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obesity-related inflammatory responses. Conversely, also influence intestinal gluconeogenesis through gut–brain
certain Gram-positive bacteria, such as Lactobacillus and signaling pathways and inhibit histone deacetylase activity
Bifidobacterium, help strengthen gut barrier function and through G protein-coupled receptor (GPCR) activation,
reduce inflammation, highlighting the potential protective thereby impacting metabolic regulation. Tryptophan
role of beneficial microbiota.
metabolism occurs through multiple pathways, including
The gut microbiota also interacts with intestinal the kynurenine and serotonin pathways. Its metabolism
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immunity, influencing both innate and adaptive products affect intestinal motility and insulin regulation,
immune responses. Immune cells, including goblet cells, with indole derivatives modulating gut hormone release
Paneth cells, and intestinal epithelial cells, maintain (e.g., GLP-1), appetite suppression, and gastric emptying.
gut homeostasis, with antimicrobial peptides (AMPs) Indole compounds also regulate immune responses by
playing a crucial role in pathogen defense. Akkermansia activating the AhR, thereby promoting IL-22 production
muciniphila, a beneficial gut bacterium, has been found to maintain mucosal immunity and gut barrier integrity.
to restore AMPs diminished by obesogenic diets, thereby
reinforcing gut protection. In addition, Toll-like receptors 4. Bacterial metabolite production from
(TLRs) and nucleotide-binding oligomerization domain- dietary components
like receptors recognize bacterial components, such as 4.1. SCFAs
LPS, flagellin, and peptidoglycan, triggering immune
activation. In adaptive immunity, the intestinal microbiota The gut microbiota plays a crucial role in energy
influences T helper 17 cells, which release interleukin (IL) production and metabolism by fermenting non-digestible
17 and IL-22, cytokines that enhance AMP production carbohydrates in the cecum, generating SCFAs, amino
and gut barrier integrity. Reduced immunoglobulin A acids, and vitamins. Among SCFAs, propionate, acetate,
(IgA) production observed in obesity has been linked to and butyrate are the most abundant, with Bacteroides
impaired immune defenses, increasing susceptibility to thetaiotaomicron primarily producing acetate and
metabolic disturbances. The gut microbiota also modulates F. prausnitzii generating butyrate. SCFAs influence
host immunity through microbial metabolites, including metabolic pathways by activating transcription factors,

Volume 2 Issue 4 (2025) 42 doi: 10.36922/MI025160036