Manipulation of Gut Microbiota as a Key Target for Crohn's Disease

Abstract

Crohn's disease (CD) is an inflammatory bowel disease (IBD) sub-type characterized by transmural chronic inflammation of the gastrointestinal tract. Research indicates a complex CD etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. The chronic mucosal inflammation has been associated with a dysregulated state, or dysbiosis, of the gut microbiome (bacteria), mycobiome (fungi), virome (bacteriophages and viruses), and archeaome (archaea) further affecting the interkingdom syntrophic relationships and host metabolism. Microbiota dysbiosis in CD is largely described by an increase in facultative anaerobic pathobionts at the expense of strict anaerobic Firmicutes, such as Faecalibacterium prausnitzii. In the mycobiome, reduced fungal diversity and fungal-bacteria interactions, along with a significantly increased abundance of Candida spp. and a decrease in Saccharomyces cerevisiae are well documented. Virome analysis also indicates a significant decrease in phage diversity, but an overall increase in phages infecting bacterial groups associated with intestinal inflammation. Finally, an increase in methanogenic archaea such as Methanosphaera stadtmanae exhibits high immunogenic potential and is associated with CD etiology. Common anti-inflammatory medications used in CD management (amino-salicylates, immunomodulators, and biologics) could also directly or indirectly affect the gut microbiome in CD. Other medications often used concomitantly in IBD, such as antibiotics, antidepressants, oral contraceptives, opioids, and proton pump inhibitors, have shown to alter the gut microbiota and account for increased susceptibility to disease onset or worsening of disease progression. In contrast, some environmental modifications through alternative therapies including fecal microbiota transplant (FMT), diet and dietary supplements with prebiotics, probiotics, and synbiotics have shown potential protective effects by reversing microbiota dysbiosis or by directly promoting beneficial microbes, together with minimal long-term adverse effects. In this review, we discuss the different approaches to modulating the global consortium of bacteria, fungi, viruses, and archaea in patients with CD through therapies that include antibiotics, probiotics, prebiotics, synbiotics, personalized diets, and FMT. We hope to provide evidence to encourage clinicians and researchers to incorporate these therapies into CD treatment options, along with making them aware of the limitations of these therapies, and indicate where more research is needed.

Conditional Vitamin D Receptor Deletion Induces Fungal and Archaeal Dysbiosis and Altered Metabolites

“…The VDR ΔPC and VDR ΔLyz knockouts promoted archaea with the potential to impact the sulfur and methane metabolism mechanisms of the host. Methanogenic archaea are associated with Crohn’s disease etiology [ 10 ]. The dramatic rise in Methanofollis after VDR deletions may predispose to IBD.…”

“…The intestinal bacteria, viruses, fungi, and archaea serve important functions in metabolism, immunity, and nervous system regulation [ 10 , 11 , 12 ]. Fungi constitute a minority of the inhabitants in the mammalian microbiome (in humans, around 0.1%) [ 13 , 14 , 15 ].…”

“…The community of intestinal fungi (collectively called “the mycobiome”) has been shown to impact host immunity, metabolism, and vitamin availability [ 13 , 15 , 16 ]. Intestinal fungi also interact with other microbes, modulating their function and abundance [ 10 , 13 , 15 , 16 ]. Finally, the mycobiome can act as a repository for opportunistic pathogens that dangerously replicate and disseminate when given the opportunity, usually due to dysbiosis or compromised immune function [ 13 , 17 ].…”

A Systematic Review of the Role of Diet in Ulcerative Colitis

“…A recent study found that FMT when combined with an anti-inflammatory diet was superior to standard medical therapy in this regard. However, it is essential to keep in mind that FMT is still regarded as an experimental treatment, and, as such, it ought to be performed only under the supervision of a qualified medical expert [5,[40][41][42].…”

Insights into the roles of bacterial infection and antibiotics in Parkinson’s disease

“…Antibiotics are used widely in treating bacterial infection diseases and have decreased the mortality rates. Until now, more and more ancillary properties are found in antibiotics, such as anti-inflammatory effects ( Moon et al., 2012 ; Rashed et al., 2022 ), inducing gastrointestinal motility ( Lam & Ng, 2011 ), and neuroprotective properties against neurodegenerative and neuroinflammatory disorders ( Sultan et al., 2013 ; Ruzza et al, 2014 ). Thus, antibiotics function as neuroprotective drugs may not only through treating bacterial infections, but also some other approaches.…”