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Microbes & Immunity Sepsis and gut microbiome

(D) Tryptophan systemic inflammatory responses post-sepsis by curbing
Tryptophan, an aromatic amino acid frequently the overactivation of inflammatory macrophages.
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employed in fluorescence dyes, acts as a precursor A positive relationship between HDCA levels and the
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for several essential metabolic pathways, particularly Eubacterium abundance was identified, proposing that
the kynurenine pathway, which holds substantial supplementing this bacterium could enhance HDCA
importance in immune regulation during sepsis. Xia production, potentially aiding in sepsis management.
et al. uncovered the role of tryptophan metabolism
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in the pathophysiology of melioidosis induced by the 4.4. Fecal microbiota transplant (FMT)
Gram-negative bacterium Burkholderia pseudomallei, FMT presents an innovative approach for tackling the
which results in pneumonia and sepsis. Employing gut dysbiosis linked to sepsis, potentially rebalancing
a comprehensive metabolic approach, their research the intestinal microbial ecosystem, safeguarding
unveiled elevated kynurenine levels and increased against intestinal damage, and modulating immune
indoleamine 2,3-dioxygenase activity, resulting in the responses. A study reported that FMT could mitigate
enhanced conversion of tryptophan into kynurenine. the immunosuppressive effects of pathogens by restoring
This process hampers T-cell proliferation and function, normal butyrate levels, exerting impacts beyond the
leading to a state of “immune paralysis” commonly intestine. However, several studies have cautioned about
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observed in the advanced stages of sepsis. This immune severe complications associated with FMT, including
suppression raises the vulnerability to secondary the risk of bacteremia. A case report by DeFilipp et al.
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infections, thereby complicating patient outcomes. documented instances of Escherichia coli bacteremia in
two patients post-FMT, which resulted in the unfortunate
4.3.3. Other metabolites
death of one patient. While FMT holds promise as a
Alongside the metabolites mentioned above, scientists therapeutic avenue in sepsis management, comprehensive
are continuously discovering novel compounds that research is imperative to thoroughly grasp its efficacy and
play pivotal roles in the progression of sepsis. Indole, safety profile in clinical settings.
a bioactive compound produced by various bacteria,
including Clostridium and Lactobacillus species, maintains 5. Conclusion
the integrity of the gut barrier. Through its actions in Recent advances in metagenomics and metabolomics
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promoting mucus secretion and tight junction assembly in have markedly enriched our comprehension of the pivotal
the intestine, indole protects the gut lining against bacterial role the gut microbiome plays in the context of sepsis. This
translocation. Moreover, indole and its derivatives, intricate microbial community serves as a cornerstone
such as indole-3-acetic acid and indole-3-aldehyde, in regulating host functions, and disruptions within it,
function as ligands for the aryl hydrocarbon receptor, known as gut dysbiosis, exert a profound influence on the
a transcription factor involved in modulating immune initiation and progression of sepsis. The intricate interplay
responses. Activation of aryl hydrocarbon receptors between the gut and the immune system presents novel
by these metabolites not only dampens the production avenues for mitigating organ injury triggered by sepsis,
of proinflammatory cytokines but also suppresses the with strategies such as fortifying gut barrier integrity,
differentiation of CD4+ regulatory T cells (Tregs). Thus, which demonstrates promise in curtailing bacterial
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indole-derived metabolites hold promise for potentially translocation. Following the depletion of gut flora
improving outcomes in conditions such as sepsis, where post-sepsis, supplementation with tailored probiotic
the need to control excessive inflammation while averting formulations emerges as a potential avenue for reinstating
immune suppression is paramount. microbial equilibrium. In addition, the utilization of
Li et al. unveiled the potential pathophysiological metabolites synthesized by these beneficial microbes,
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role of gut-derived rhamnose in enhancing macrophage including SCFAs and essential amino acids, in the
phagocytic activity through its interaction with the formulation of specialized nutritional supplements holds
SLC12A4 protein, a vital element in the host’s defense promise in bolstering the recovery of critically ill patients.
against polymicrobial sepsis. Other bioactive metabolites Interventions aimed at modulating gut microbiomes,
such as L-valine have shown promise in preserving such as FMT, exhibit potential for patients grappling with
intestinal barrier integrity, with findings indicating a dysbiosis. However, the optimal patient selection, timing
negative correlation with APACHE-II and SOFA scores, of intervention, and administration protocols for FMT
critical indicators of sepsis severity. Moreover, the warrant further investigation. In summation, a more
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secondary bile acid hyodeoxycholic acid (HDCA), derived comprehensive understanding of the gut microbiome
from primary bile acids by gut microbiota, could mitigate harbors the potential to unveil innovative strategies that

Volume 2 Issue 1 (2025) 10 doi: 10.36922/mi.4742