The human gut microbiome is a major factor in the development of sepsis, yet the dearth of human studies means limited new treatments that use the microbiome as a way to effectively treat bacterial sepsis, according to a review published in Journal of Infectious Diseases.
The authors note that most research on sepsis in humans has focused on the dysregulated immune response of the host, while research implicating the gut microbiome as a major factor in sepsis risk is well documented only in animals. A disrupted gut microbiome may play a role in organ dysfunction across multiple systems, a hallmark of severe sepsis.
At the molecular level, the microorganisms interact with components of the host’s immune system via an ever-evolving “bacterio-immune crosstalk”. Microorganisms use contact-dependent mechanisms to influence local barrier function at the site of colonization, hematopoiesis, T-cell differentiation and activation, cytokine production, antibody production, and phagocytosis.
Bacteroides And the packetThey are the most abundant bacterial phylum in the gut, and are an important producer of short-chain fatty acids, which can regulate gene expression in regulatory T cells and change how macrophages kill bacteria.
A healthy gut microbiome, dominated by obligate anaerobes germs And the packet, establishes resistance to colonization of typically low-level, highly pathogenic species in the gut, such as Enterococcus faecalis And the Klebsiella pneumoniae.
However, within minutes or hours of the introduction of a stress into the gut such as tissue injury or infection, there is a loss of binding anaerobes. Artificial feeding and antibiotics, which are hallmarks of sepsis management, further disrupt the intestinal microbiome, leading to sepsis.
The authors therefore emphasize that treatment of sepsis should be guided by the relationship between bacteriological outcomes and sepsis outcomes.
First, clinicians should follow community guidelines on antibiotic stewardship because antibiotics are necessary to treat sepsis despite their effect on the gut microbiome. In addition, oral scavenger compounds should be used to reduce antibiotic inactivation of the gut microbiota while maintaining systemic therapeutic levels. The authors acknowledge that more clinical studies of oral scavengers are needed.
Second, artificial nutrition should contain more fiber to support a healthy microbiome. Synthetic feeding typically consists of a sterile, chemically defined casein-based diet that lacks any dietary fiber, and studies have shown that patients fed a low-fiber diet based on animal protein develop intestinal conditions that inhibit the growth of Firmicutes and Bacteroidetes.
Finally, the authors highlight prebiotics, fermented fiber additives for those receiving enteral nutrition, and FMT as alternative treatments. However, they noted, “Currently, therapies that target the microbiome are still largely under investigation, and judicious use of antibiotics and a rethinking of current food formulations remain the only therapeutic interventions that can be recommended based on current evidence.”
Miller D, Kesky R, Alverde J. Sepsis and the microbiome: a vicious cycle. J Infect Dis. Published online December 17, 2020. doi: 10.1093/infdis/jiaa682