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Microbes & Immunity Sepsis and gut microbiome

phenylpyruvate in boosting macrophage bactericidal improving gut health in various diseases, their application
activity and reducing multiple organ dysfunction in sepsis and critically ill patients in ICU is underexplored.
syndrome for patients with bacterial sepsis. In addition,
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another research group revealed that a reduced abundance 4.3. Postbiotics
of Parabacteroides during pregnancy could exacerbate 4.3.1. Short-chain fatty acids (SCFAs)
inflammation and worsen sepsis outcomes. Treatment with
Parabacteroides merdae and its metabolites, particularly The gut microbiota metabolites are essential for maintaining
formononetin, can protect against septic inflammation by the fundamental functions of the host in a healthy state.
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inhibiting macrophage pyroptosis. Together, probiotics Disruptions in the production of these metabolites can
hold promise as a complementary approach to managing lead to a range of diseases, including metabolic disorders,
cardiovascular issues, and gastrointestinal ailments.
sepsis, offering a novel avenue for therapeutic intervention
in this critical condition. SCFAs are metabolites produced by the gut microbiome
through the fermentation of dietary fibers. These SCFAs,
4.2. Prebiotics primarily acetate, propionate, and butyrate, play a
crucial role in communicating between the gut and the
Prebiotics are non-digestible compounds that can be 75
selectively metabolized by gut microorganisms, providing immune system. Acetate is the most abundant SCFA,
significant benefits to the host. While certain non- produced extensively by bacteria such as Prevotella spp.,
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carbohydrate compounds such as polyphenols and Bifidobacterium spp., and Akkermansia muciniphila.
polyunsaturated fatty acids can function as prebiotics, Acetate has been shown to regulate immune responses in
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most prebiotics are carbohydrate-based. 68 Low- various disease contexts, including colitis and arthritis.
molecular-weight carbohydrates are efficiently converted Notably, acetate can also modulate the brain’s immune
by bacteria. Key examples include fructans (such as system, as demonstrated by its ability to influence
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fructooligosaccharides and inulin [FOS]) and galactans microglia during neurodegeneration. The depletion of
(such as galactooligosaccharides [GOS]), which promote SCFAs due to antibiotic disruption of the gut microbiome
the growth of beneficial bacteria such as Lactobacillus can lead to hyperresponsive macrophages, a condition
and Bifidobacterium. Clinical studies have demonstrated that disturbs gut immune homeostasis. Significantly,
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the potential of prebiotics such as inulin to improve the supplementation of butyrate alters the activation of
inflammation in conditions such as ulcerative colitis these macrophages, restoring a more balanced immune
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by enhancing the abundance of butyrate-producing response. In addition, broad-spectrum antibiotics have
Firmicutes. In addition, inulin has been shown to modulate been found to promote the colonization of invasive fungi
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gut microbiota, including Bacteroides and Parabacteroides, by decreasing SCFA-producing Clostridium species. In
to suppress diet-induced non-alcoholic steatohepatitis. the context of sepsis, SCFAs have been shown to affect
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FOS and GOS have similarly demonstrated their ability sepsis-induced encephalopathy by protecting cognitive
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to regulate inflammatory responses, with clinical trials function and altering the polarization of microglia. These
showing that GOS combined with Bifidobacterium studies highlight the critical role of SCFAs in maintaining
improves intestinal barrier function. 72,73 In addition, gut-immune communication and modulating immune
other simple carbohydrates such as lactulose also showed responses.
a protective effect on intestinal epithelium against the 4.3.2. Amino acids
colonization of Klebsiella pneumonia. Despite these
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promising findings, the use of prebiotics in sepsis remains Bacteria in the gut can produce both essential and non-
limited. essential amino acids, including glutamine, arginine, and
tryptophan. These amino acids contribute to a variety
Several challenges contribute to the scarcity of
research on prebiotics in sepsis. One key issue is of physiological processes, such as immune regulation,
neurotransmitter synthesis, and gut barrier maintenance.
impaired gastrointestinal function, including reduced However, the composition and function of these amino
gut motility and disrupted nutrient absorption, which
limit the effectiveness of orally administered prebiotics. acid-producing bacteria can be significantly altered during
Furthermore, many ICU patients rely on parenteral or and after sepsis or other infectious events. These disruptions
enteral nutrition, where prebiotics may not be well tolerated to the gut microbiome can lead to dysregulation in amino
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or easily incorporated. There is also concern that prebiotics acid metabolism.
stimulating bacterial growth may increase bacterial (A) Glutamine
translocation and worsen systemic infections. While Glutamine, produced by gut bacteria such as Bacteroides
prebiotics show potential in regulating inflammation and and Clostridium, contributes to the proliferation of intestinal

Volume 2 Issue 1 (2025) 8 doi: 10.36922/mi.4742