Page 12 - MI-2-1

Microbes & Immunity Sepsis and gut microbiome

consist of antibiotics and supportive care, with limited systems. Reduced intestinal diversity has been linked to
options for targeted therapies. Therefore, comprehending unfavorable outcomes in critically ill patients due to its
6
the underlying mechanisms of sepsis and developing novel susceptibility to influences such as antibiotic therapy.
therapeutic strategies is crucial. A study on septic patients in a Chinese cohort revealed that
α-diversity was initially similar between septic and non-
The gut microbiome is a complex ecosystem that
plays a crucial and active role in its host. The microbial septic cases on day 1, but within a week, septic patients
exhibited a significant drop in diversity compared to the
inhabitants in our gut consist of approximately 100 trillion control group. An investigation into intensive care unit
17
cells, outnumbering the cells that make up the human (ICU) patients’ fecal microbiota discovered a decreased
body by 10 folds. The gut microbiome contains about presence of Faecalibacterium prausnitzii, known for its
7
2 – 4 million genes, showcasing a vast diversity of 100 – anti-inflammatory function, in both septic and non-
150 times greater than the human genome. The advent septic individuals. Furthermore, a multicenter study
8,9
18
of 16S rRNA sequencing and metagenomics enables us to involving 155 ICU patients found that septic patients
delineate the microbial profile effectively. Through these had elevated levels of harmful intestinal microbiota such
10
techniques, the gut bacterial species in healthy volunteers as Parabacteroides, Fusobacterium, and Bilophila species
primarily comprise three phyla: Bacteroides, Firmicutes, in perirectal swabs. These microbes are associated with
19
and Actinobacteria. Over the years, evidence has indicated endotoxin production, increased mortality risk, and
11
that the gut microbiota may play a crucial role in sepsis. heightened inflammation, further disrupting metabolic
12
Studies utilizing sequencing methods have elucidated that and immune homeostasis. 20,21
microbiota imbalance, such as reduced microbial diversity
and an abundance of microbial genes, could be impacted 2.2. Factors contributing to dysbiosis
by sepsis and vice versa. 13,14
Critically ill patients are more prone to experiencing
Protein-calorie malnutrition is prevalent among critically disruptions in their intestinal microbiota. While the
ill patients, often resulting from a combination of factors such precise causal mechanisms remain unclear, various factors
as anorexia, diarrhea, and decreased body mass, all influenced can contribute to disturbances in the gut microbiome,
by the inflammatory response and hypermetabolism. encompassing extrinsic influences such as antibiotic
15
The dysregulated gut microbiota plays a crucial role in the treatments and intrinsic factors like disease and systemic
initiation and progression of sepsis. Patients with sepsis inflammation.
commonly exhibit gastrointestinal dysfunction marked by In ICUs, antibiotics, particularly broad-spectrum
issues such as altered gut motility and permeability, which ones, are commonly administered to patients suspected
can severely hinder digestion and absorption, thereby of sepsis before bacteriological results are available.
exacerbating inflammation and contributing to multiorgan A large epidemiological study spanning 500 hospitals
failure. Given the gut’s crucial function in metabolizing revealed that exposure to high-risk antibiotics during
dietary compounds into bioactive molecules, gastrointestinal hospitalization could disrupt patients’ microbiota,
dysfunction during sepsis can significantly impact the potentially heightening the risk of sepsis. These high-
22
production of protective metabolites. 16 risk exposures comprised third- or fourth-generation
While some aspects of gut dysbiosis have been cephalosporins, fluoroquinolones, lincosamides, β-lactam/
elucidated, a more comprehensive understanding of β-lactamase inhibitor combinations, oral vancomycin,
how gut microorganisms influence the sepsis process is and carbapenems. Their findings identified that patients
required. This review aims to deepen our understanding of exposed to cephalosporins, vancomycin, and β-lactamase
the intricate relationship between gut microorganisms and inhibitors exhibited a heightened association with the
22
sepsis (Figure 1). It specifically focuses on elucidating the development of sepsis and septic shock. Long-term
changes in gut microorganisms, their functional effects, antibiotic administration may lead to the development
and the role of microbial-derived metabolites in sepsis, and of resistant gut flora such as vancomycin-resistant
explores potential therapeutic strategies targeting sepsis Enterococcus faecium (VRE) 23,24 and Clostridium difficile
25
through modulation of the gut microbiome. infection. These alterations and disruptions in the gut
microbiota can result in bacterial translocation, facilitated
2. Gut dysbiosis in sepsis by increased intestinal permeability and compromised
gut barrier integrity, potentially exacerbating systemic
2.1. Sepsis-induced microbiome change
inflammation. Besides, Mu et al. described that VRE
26
The pathophysiology of sepsis is intricately complex, and Klebsiella are predominant in the gut, potentially
involving various infection sites and failing organ leading to secondary infections in septic patients following

Volume 2 Issue 1 (2025) 4 doi: 10.36922/mi.4742