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Microbes & Immunity                                                              Management of obesity



            activation. Psychological stress can trigger hedonic   Several factors influence early microbiota development,
            signaling pathways, leading to increased consumption of   including mode of delivery, maternal microbiota, feeding
            high-calorie foods. In addition, bacterial fermentation   practices, antibiotic exposure, and dietary changes. The
            products, such as propionate have been linked to reduced   maternal gut microbiota directly affects infant colonization,
            reward responses to unhealthy food, thereby influencing   with Bifidobacteria being a dominant species transmitted
            feeding behavior. 55                               through breast milk and fecal matter.  Mode of delivery
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                                                               also plays a significant role in microbiota composition, with
            8.7. Chronic inflammation                          vaginally born infants showing higher levels of Bacteroides,
            Chronic low-grade inflammation is a key trait of obesity,   while Cesarean-section-delivered infants exhibit increased
            primarily driven by increased levels of LPS – endotoxins   levels of  Hungatella. Feeding practices shape microbial
            released by Gram-negative bacteria, such as Veillonella. In   diversity – formula feeding leads to greater microbiome
            obese individuals, excessive LPS disrupts the gut barrier   development compared to breastfeeding. In addition,
            by activating the TLR4/myeloid differentiation primary   antibiotic  use  rapidly  alters  the  gut  microbiota,  reducing
            response 88 (MyD88)/IL-1 receptor-associated kinase 4   beneficial bacterial populations, while dietary changes,
            (IRAK4) signaling pathway, allowing bacterial byproducts   such as the introduction of complementary foods, further
            to enter the bloodstream. Reduced levels of A. muciniphila,   influence microbiome diversity. 58
            which helps maintain gut barrier integrity, further
            contribute to this process. In addition, high-fat diets (HFD)   9.2. Composition of the adult microbiota
            facilitate LPS absorption and transport into circulation   In healthy adults, the gut microbiota is comparatively
            through chylomicrons. Once in the bloodstream, LPS   stable, unlike in infants, whose microbiome is still
            triggers immune responses in adipose tissue and the liver.   developing, and the elderly, who tend to have a less
            It forms complexes with LPS-binding protein and cluster   diverse and more unstable gut microbiome (Figure 2). The
            of differentiation 14, leading to the stimulation of nuclear   dominant bacterial phyla in the adult gut microbiota are
            factor  kappa  B (NF-κB)  and activator  protein  1, which   Firmicutes and Bacteroidetes, alongside other phyla, such as
            drive the release of pro-inflammatory cytokines, such   Actinobacteria, Verrucomicrobia, and Proteobacteria. While
            as TNF-α, IL-6, and monocyte chemoattractant protein   microbial diversity varies among individuals, gut bacteria
            (MCP) 1. These cytokines, in turn, stimulate adipocytes   consistently perform essential physiological functions,
            to  secrete  additional  inflammatory  signals,  exacerbating   including metabolism, fermentation, methanogenesis, and
            metabolic dysfunction. Despite the inflammatory effects of   immune regulation. 59
            LPS, SCFAs – especially butyrate – exert anti-inflammatory   However,  several  factors  can  disrupt  microbiota
            properties. Butyrate promotes IL-18  secretion, supports   homeostasis, including host genetics, diet, medications,
            regulatory T cell differentiation, and suppresses NF-κB   infections, and circadian rhythm disturbances.  Diet-
            activation, thereby reducing inflammation.  However,   induced obesity is associated with shifts in microbiota
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            it remains unclear whether these beneficial effects are   composition that differ from those of normal-weight
            sufficient to counteract LPS-induced chronic inflammation,   individuals. Antibiotics and other xenobiotics can rapidly
            indicating the need for further research.          alter microbiome diversity and function, and prolonged
            9. Factors affecting homeostasis                   exposure may lead to antibiotic resistance and microbiome
                                                               imbalance. Maintaining a stable microbiota is critical for
            9.1. Composition of infants’ microbiota            immune system homeostasis, as it helps resist pathogenic
            The composition and development of the infant gut   infections; however, infections can significantly disrupt
            microbiota differ  significantly  from that  of adults,   microbiota composition. In addition, circadian rhythm
            undergoing a dynamic process of establishment.     plays a role in microbiota balance – disruptions in feeding
            Colonization begins at birth, with some evidence suggesting   patterns  can  lead  to  gut  flora  imbalances  and  metabolic
            maternal bacterial transmission may occur during gestation.   disorders, including obesity. Overall, maintaining gut
            In neonates, the gut microbiota consists primarily of   microbiota stability is essential for supporting metabolic
            Enterococcus, Escherichia/Shigella, Streptococcus, and Rothia   health and immune function, with various internal and
            species, while infants aged 1 – 6 months show increased   external factors influencing its composition and resilience. 60
            colonization of  Bifidobacterium and  Collinsella. By   10. Alteration of gut microbiota by
            4 months of age, additional bacteria, such as Lactobacillus,
            Granulicatella, and Veillonella become prevalent, although   antibiotics leading obesity
            full microbiome maturation continues until at least two   Diet and antibiotics play a fundamental role in shaping
            years of age, reaching adult-like complexity by age three.   gut  microbiota  composition,  with  diet  exerting  a  more


            Volume 2 Issue 4 (2025)                         48                           doi: 10.36922/MI025160036
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