Relationship Between Gut Microbiota And Sepsis

Introduction:

For many years, the gut has been thought to play a role in the pathogenesis of sepsis (this involves complex response of cellular activities that trigger proinflammatory mediators). Life-threatening organ dysfunction is called sepsis and is caused by a dysregulated host response to infection. Organ failure assessment for sepsis focuses on respiratory, hepatic, renal, neurological, hematological, and cardiovascular systems. The intestinal composition of the microbiome is affected by sepsis and contributes to organ failure.

What Is Gut Microbiota?

Human beings harbor around 10 trillion to 100 trillion microbial cells in a symbiotic relationship. The gut microbiota is the system of microorganisms in an individual's gastrointestinal tract. This includes fungi, bacteria, viruses, and other organisms. These organisms have a symbiotic relationship with the human digestive system and help in immune defense and digestion. They mainly reside in the intestine. They play a key role in digestion control, benefiting the immune system and contributing to causing high blood sugar, weight gain, high cholesterol, and other disorders. Many health issues can thrive if an imbalance in gut microbiota occurs.

What Is Sepsis?

Sepsis is a life-threatening condition that leads to organ dysfunction caused by a dysregulated host response to infection. Almost 20% of deaths all over the world occur due to sepsis. During sepsis, the microbiota is profoundly distorted with a sharp decrease in diversity, overgrowth of pathogenic bacteria, and loss of commensal bacteria. Altered gut microbiota influences inflammatory responses and increases gut barrier permeability and enables translocation of pathobionts.

What Are the Symptoms of Gut Microbiota Imbalance?

Imbalance in gut microbiota can lead to :

• Unintentional weight changes.

• Nausea and vomiting.

• Loss of appetite.

• Fever.

• Skin rashes.

• Food intolerance.

• Autoimmune conditions.

• Disturbed sleep patterns.

• Sugar cravings.

• Stomach upset.

What Are the Microbiota Disorders Related to Sepsis?

In sepsis, the factors like hypoxia injury, intestinal motility dysfunction, inflammation, and destruction of epithelial cell integrity can change the proportion and composition of gut microbiota. Some harmful bacteria like Trichinella spiralis and Vibrio cholera can induce mucin degradation and inhibit mucin production. Lactobacillus SPP (gut bacteria) can stimulate mucin 3 and mucin 2 production and secretion. The microbial metabolite SCFA's (short chain fatty acids) can also encourage mucin 2 expression. Gut micro-ecological collapse can result in sepsis and a dominant genus changes from common symbiotic bacteria to a pathogenic genus.

The healthy bacterial function also decreases. The gut flora of individuals with septic shock is characterized by low population diversity and a high degree of individualization associated with excessive reproduction of a single genus. Studies reveal that gut microbiota is involved in the pathogenesis of late-onset sepsis and is its main risk factor.

What Is the Relation Between Gut Microbiota and Systemic Immunity?

Gut microbiota not only plays an important role in innate and intestinal mucosal immunity. But affects intestinal microcirculation through inflammation and vascular reaction.

• IgA secreting cells and CD4+T cells are reduced. The destruction of a balanced gut could cause an immune system response, leading to inflammatory reactions and ultimately destroying the mucosal barrier.

• The gut flora affects the systemic immune response by regulating several key pathways, including production of SCFA, control of inflammatory T cells populations, oral immune tolerance, and expansion and differentiation of extraintestinal T-cells.

• Disordered gut flora can induce decreased number and differentiation of dendritic cells, increase susceptibility to pathogenic microorganisms and suppress T Cell immune responses in sepsis.

• The flora dysbiosis can induce macrophages that differentiate into M1 type and release TNF (tumor necrosis factor) alpha, IL-1, and IL (interleukins)-6, which aggravates inflammation and reaction in sepsis.

How Does Gut Microbiota Affect Organ Dysfunction?

• The integrity of the gastrointestinal barrier is destroyed by LPS (lipopolysaccharides), partly due to the weakening of altering mucosal hydrophobic properties and bile components. This can cause bile acid reflux and gastric bleeding and reduce bile salts in the ileum.

• Phosphatidylcholine containing a hydrophobic layer protects and covers the surface of the gastrointestinal tract and helps in maintaining barrier integrity.

• In sepsis, the integrity of the intestinal (gut) barrier is impaired by PC (Phosphatidylcholine) degradation. It also induces high intestinal permeability and epithelial cell apoptosis.

• Heparin-binding protein levels associated with gastrointestinal dysfunction are positively related to sepsis.

• Klebsiella pneumoniae infection leads to many changes in gut microbiota and metabolome (small molecule that is found in organ ,cell, or organism). The gut microbiota and SCFA form a protective effect on lung injury. They directly contribute to organ dysfunction other than lung during sepsis.

• The gut microbiota reaches the liver through a portal vein, which promotes capture and killing by circulating pathogens by kupffer cells.

• Death of microbiota by the use of antibiotics can lead to a failure in pathogen clearance and diffuse infection. Microbiota is considered a key player in liver disease by interacting with inflammatory signals and bile acid.

• Gut microbiota cannot only cause delirium directly through inflammatory pathways but can also lead to acute brain dysfunction through the translocation of bacteria to the brain during sepsis.

What Are Microbial Therapy for Sepsis?

The therapies used for treating sepsis are:

• Probiotics reduce the severity, incidence, and duration of respiratory infections in adults, children, and the elderly. The association between probiotic use in critically ill individuals and infection risk remains to be verified.

• Fecal microbial therapy (FMT) has shown a potential therapeutic effect in many diseased conditions that are affected by Clostridium difficile infection. FMT enhances the clearance of pathogens by restoring host immunity and reversing fatal sepsis related to the proliferation of butyrate-producing bacteria.

• Fecal bacterial liquid, transplantation methods, and subsequent treatment are unified approaches for selecting donors.

• SSD (selective decontamination of the digestive tract) is the most controversial treatment. Here local antibiotics are used to suppress potential pathogens while maintaining colonization resistance. A meta-analysis shows that SDD can prevent secondary infection and reduce overall mortality in critically ill individuals.

• Recently, traditional Chinese medicines have been used to improve gut microbiota disorders. Using Jinzhi and Xuan Bai Cheng Qi decoction can restore damage to tight binding protein occluding of gut epithelium and improve intestinal barrier dysfunction.

Conclusion

Gut and intestinal flora are essential in maintaining homeostasis in the host. Gut microbiota dysbiosis may be widespread and plays a main role in the pathogenesis of sepsis, which leads to organ dysfunction. Microbial targeted therapy is shown to improve the prognosis of sepsis. However, studies are still required to experiment on their effectiveness and safety.