**3. The gut microbial metabolites in the pathogenesis of sepsis**

It was shown that in vitro some sepsis-associated AMM in clinically significant concentrations can inhibit the phagocytic activity of neutrophils [17]; cause mitochondrial dysfunction [18]; influence on platelet aggregation [19]; reduce tyrosine hydroxylase activity, thus limiting the synthesis of catecholamines; and participate in the pathogenesis of septic shock [20]. Numerous data obtained in vitro allow us to hypothesize that AMM acts as signaling molecules (**Figure 3**).

It is impossible to exclude the presence of common signaling pathways, cell receptors, transmembrane transporters, and other mechanisms of humans and bacteria, as well as the direct participation of microbial metabolites in the pathogenesis of sepsis. Thus, today, we should not confine ourselves to studying eukaryotic cells while searching for new molecular mechanisms of sepsis-associated organ failure and septic shock [20]. We should consider

**Figure 3.** Schematic representation of levels of some biochemical parameters, metabolites, and hormones in blood serum in comparison.

In particular, serum samples of healthy people are characterized by a predominance of BA and PhPA, while hydrophilic AMMs are detected in sepsis with the appearance of high levels of HVA in the serum of non-survivors. BA is a product of the synthesis of bacteria, plants, and fungi, but a significant content is formed as a result of biodegradation of phenylalanine.

**Figure 2.** Metabolic profile of aromatic metabolites in: (A) the gut and (B) the blood serum. The data are presented by

**Figure 1.** Taxonomic composition of the gut microbiota by metagenomic analysis. Comparison the taxonomic

composition of the gut microbiota: (a) at the major phylum and (b) by top 10 families.

28 Infectious Process and Sepsis

median of the proportion of each acid among all AMMs.

and simulate experimental changes in the internal environment of a person that occur with a radical "restructuring" of the microbiome in seriously ill patients. This approach opens new prospects for an objective monitoring of diseases, carrying out an assessment of the integral metabolic profile on common metabolites (particularly aromatic) within a given time, and will provide new targets for therapeutic effects in the future.

**Study Population Type of intervention Results**

15 patients with early sepsis The multispecies

Meta-analysis of 30 trials that enrolled 2972 critically ill patients

Meta-analysis of 31 articles that enrolled 2952 surgical patients

298 patients with predicted severe acute pancreatitis

*Clostridium difficile* infection (CDI) with a focus on FMT

Meta-analysis of 5 trials that enrolled 284 patients with CDI

Review of clinical use of fecal microbial transplantation in critical illness

patients

4556 healthy newborns *Lactobacillus plantarum* Reduction in the

Microbiota-Oriented Diagnostics and Therapy in Sepsis: Utopia or Necessity?

probiotic in a dose of 109 daily

Different types of probiotic therapy

Different types of probiotic, prebiotic and symbiotic therapy

4 species of lactic bacterial (*L. acidophilus*, *L. casei*, *L. salivarius*, *L. lactis*), and 2 species of bifid bacteria (*B. bifidum*, *B. lactis*) in a dose of 1010 daily

FMT (including autologous FMT)

incidence of sepsis during the first 60 days of life

31

http://dx.doi.org/10.5772/intechopen.89187

Probiotic intervention successfully modulates the microbiome

Probiotics were associated with a significant reduction in infections (risk ratio 0.80, 95% confidence interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I2 = 36%, P = 0.09)

Symbiotic therapy was the best regimen in reducing surgical site infection (SSI) (RR = 0.28; 95% CI, 0.12–0.64)

Probiotic prophylaxis is associated with an increased risk of mortality and higher rate of infectious complications

therapy but not enough data in the ICU patients

FMT was statistically significantly more effective (RR, 0.41; 95% CI, 0.22–0.74; NNT, 3; 95% CI, 2–7) than vancomycin or placebo

mitigate multiple organ dysfunction in the ICU

a severe infection and one death from fecal transplants containing drug-resistant bacteria

FMT The potential effective

FMT An attractive option to

FMT The development of

Probiotics/symbiotics

☺ Panigrahi

☺ Stadlbauer

☺ Manzanares

☺ Kasatpibal

☺ Besselink

☺ Moayyedi

☺ McClave et al.

FMT

et al. [21]

et al. [22]

et al. [23]

et al. [24]

et al. [25]

et al. [27]

[28]

☺ Han et al. [26] Review of management of

☺ FDA [29] Two immunocompromised
