Immunological consequences of microbiome-based therapeutics

Abstract

The complex network of microscopic organisms living on and within humans, collectively referred to as the microbiome, produce wide array of biologically active molecules that shape our health. Disruption of the microbiome is associated with susceptibility to a range of diseases such as cancer, diabetes, allergy, obesity, and infection. A new series of next-generation microbiome-based therapies are being developed to treat these diseases by transplanting bacteria or bacterial-derived byproducts into a diseased individual to reset the recipient’s microbiome and restore health. Microbiome transplantation therapy is still in its early stages of being a routine treatment option and, with a few notable exceptions, has had limited success in clinical trials. In this review, we highlight the successes and challenges of implementing these therapies to treat disease with a focus on interactions between the immune system and microbiome-based therapeutics. The immune activation status of the microbiome transplant recipient prior to transplantation has an important role in supporting bacterial engraftment. Following engraftment, microbiome transplant derived signals can modulate immune function to ameliorate disease. As novel microbiome-based therapeutics are developed, consideration of how the transplants will interact with the immune system will be a key factor in determining whether the microbiome-based transplant elicits its intended therapeutic effect.

Past, present, and future of microbiome-based therapies

“…These bacteria are believed to play fundamental roles in human health status, contributing to the maintenance of gut homeostasis, supporting the function of the immune system, and protecting against certain pathogens [ 15 , 95 ] . Several in vitro and clinical trials have studied the general beneficial effects of different orally administered probiotics on host health, as well as their role in different diseases [ 96 ] .…”

“…Most of the currently existing postbiotics are derived from bacteria of the Lactobacillus or Bifidobacterium bacterial genera, but also from yeasts such as Saccharomyces cerevisiae , mainly from the fermentation of these bacteria carried out in industrial processes [ 100 - 105 ] . Postbiotics are commonly metabolites or polysaccharides, substances with antioxidants, anti-inflammatory or even immunomodulatory properties [ 15 , 95 , 100 ] . One of these interesting metabolites is SCFAs, a product of bacterial fermentation of dietary fiber in the colon [ 15 ] .…”

“…Postbiotics are commonly metabolites or polysaccharides, substances with antioxidants, anti-inflammatory or even immunomodulatory properties [ 15 , 95 , 100 ] . One of these interesting metabolites is SCFAs, a product of bacterial fermentation of dietary fiber in the colon [ 15 ] . Thus, an important challenge in the development of postbiotics is the identification and isolation of the bioactive metabolites or proteins produced by these bacteria, usually done by chromatographic or metabolomic techniques [ 100 ] .…”

Bacteria associated with glioma: a next wave in cancer treatment

“…They are naturally targeted to tumors in hypoxic and necrotic regions. In addition to targeting molecular targets such as tumor proteins and antigens, bacteria-based treatment may also target tissue-level pathological alterations ( Alam et al., 2022 ). Employ recombinant DNA technology to boost the antitumor impact of engineered bacteria via directed genetic alteration ( Xia et al., 2020 ).…”

Host Immune Responses to Clostridioides difficile Infection and Potential Novel Therapeutic Approaches

“…However, the precise mechanisms through which live biotherapeutics offer protection against CDI are not yet fully understood. Nevertheless, it is believed that the restoration of a dysbiotic gut environment with beneficial bacteria and their associated metabolites is one potential mechanism [ 83 , 85 , 86 ].…”