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Microbes & Immunity Sepsis and gut microbiome

the host from invasions within the gut. Furthermore, zones. In germ-free mice, ILFs can be supplanted by a
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mesenteric lymph nodes (MLN), Peyer’s patches (PPs), majority of Lin c-kit IL-7Rα RORγt cells known as
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and smaller isolated lymphoid follicles (ILF) are critical cryptopatches, which, upon interaction with commensal
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components of this complex immune system network. bacteria, initiate the development of ILFs. Deficiencies
MLNs are the most prominent lymph nodes in the body, in CXCL13, CXCR5, or RORγt may result in the failure
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comprising both cortex and medulla. During sepsis, of cryptopatches from maturing into ILFs. Recently,
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circulating lymphocytes migrate to the T-cell zone of MLNs, Wu et al. shed light on the connection between the
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where DCs then present antigens to the T-cells. Research complement system and gut immunity by identifying
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by Darkwah et al. revealed a significant increase in CD4 the presence of C3-expressing cells within ILFs. Studies
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T-cell proliferation by mucosal MLN DCs in the CLP have shown that sepsis can reduce the quantity and size
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septic model compared to systemic DCs from the spleen, of lymphoid follicles. Notably, patients with sepsis
indicating a gut-derived pathway to systemic circulation exhibit a decrease in B-cell areas and lymphoid follicle
triggered by bacterial translocation. In addition, O’Boyle counts compared to trauma patients without sepsis. This
et al. identified similarities between organisms in the depletion is particularly pronounced in patients with
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MLN and the pathogens responsible for sepsis in surgical prolonged septic episodes. The development of ILFs
patients, lending credence to the gut-origin hypothesis for necessitates lymphoid-inducer cells capable of secreting
sepsis onset. IL-17 and IL-22, both components of the Th17 signature.
In sepsis, IL-17-producing cells such as Th17 and γδ
PPs are distributed throughout the small intestine, T17 cells are recognized for their pro-inflammatory
with the highest concentration typically found in the nature and their potential role in exacerbating sepsis-
ileum. They comprise lymphoid follicles characterized by a related conditions. These cells may infiltrate the brain,
germinal center, subepithelial dome, and follicle-associated leading to sepsis-associated encephalopathy, or migrate
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epithelium. The germinal center is densely populated with to the lungs, worsening sepsis-induced acute lung injury.
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proliferating B lymphocytes, DCs, and macrophages. In These observations highlight a plausible link between
contrast, the subepithelial dome contains a mix of B and T sepsis and the development of ILFs.
lymphocytes, along with DCs and macrophages. PPs have
the unique ability to sample luminal antigens by crossing 4. New strategies for treatment of sepsis
the epithelial barrier through specialized microfold cells 4.1. Probiotics
that secrete macromolecules. The primary role of PPs lies
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in their communication with the enteric nervous system, Recent studies have revealed that specific microbial
thereby contributing to the microbiota-gut-brain axis. supplements hold the potential to bolster immune
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Under normal conditions, DCs within PPs detect mucosa- responses and alleviate the severity of sepsis. The
associated bacteria, triggering the production of IL-6 and PRIMAL clinical trial, for instance, has provided evidence
IL-23, which in turn regulate IL-17 and IL-22 levels in T that probiotics Bifidobacterium and Lactobacillus can
cells and innate lymphoid cells. Nonetheless, evidence effectively ameliorate gut dysbiosis in preterm infants,
regarding the immune function of PPs in sepsis remains potentially lowering the risk of severe conditions such
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limited. Schulz et al. reported that Salmonella infection as sepsis and necrotizing enterocolitis. In a separate
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triggered the hypertrophy of PPs and identified the IFNAR/ randomized clinical trial investigating probiotic effects
CD69/S1PR1 axis, which facilitates the lymphocyte egress on cytokine levels in children with severe sepsis, a notable
during infection. Conversely, Fan et al. demonstrated decrease in pro-inflammatory cytokines and an increase
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reduced PPs cell yield and CD4+T cell count in the CLP in anti-inflammatory cytokines were observed. This trial
model. involved the administration of a combination of four
Lactobacillus strains (Lactobacillus paracasei, L. plantarum,
ILFs, a specialized type of tertiary lymphoid organs, L. acidophilus, and L. delbrueckii), three Bifidobacterium
are notably smaller than PPs and feature a microfold- strains (Bifidobacterium longum, B. infantis, and B. breve),
cell surface epithelium. Despite their significance, and Streptococcus. Furthermore, Xie et al. discovered
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there is limited understanding of ILFs in the context of that supplementation with the emerging probiotic
sepsis. These structures typically develop in response to Akkermansia muciniphola, along with its supernatant,
microbial antigens and dietary components in healthy can reduce sepsis-induced mortality in a CLP model. In
individuals, yet in certain pathological conditions, this study, they identified a novel tripeptide, Arg-Lys-His
such as trauma, infection, or other irritations, their (RKH), as an endogenous antagonist for Toll-like receptor
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formation can be triggered. ILFs are characterized by 4 (TLR4). They also highlighted the increasing significance
a sparse population of T cells and lack distinct T-cell of Candida albicans and its derivative metabolite

Volume 2 Issue 1 (2025) 7 doi: 10.36922/mi.4742