THE ROLE OF THE MICROBIOTA

THE ROLE OF THE MICROBIOTA

The microbes in our body, website like this especially in the gut, play important part in relation to nutrition and on human physiology.  Microbes are important for human life and all changes may influence the health of the host.  Bowel diseases have been associated with changes of the gut microbiome.[1],[2],[3],[4],[5]  Beneficial homeostasis between the host and the microbiota must be ensured by restricted microbial growth in the intestines, where the mucosal immune system operates and tight regulation of the gut microbiota prevents chronic inflammation in the host. Several aspects of the immune tissues in the host are developed and directed by the intestinal microbiota, as well as immune cell populations and immune mediators.[6]

According to Bensussan et al[7] the microbiota does influence the immune and metabolic pathways, general health and disease e.g. in gastrointestinal diseases, and even immunological diseases which are outside the gut.  Probiotics are beneficial for the microbiota and evidence reveal effective outcome in suppressing asthma, decreasing flue-like symptoms in children, lowering cholesterol levels and an effective protection against infection.[8],[9],[10],[11],[12]

DIET-INDUCED Dysbiosis in Cronh´s Disease (CD)

According to Turnbaugh et al[15] dysbiosis was detected in “humanized mice” in a single day by shifting their diet from a low fat, plant based diet to a high fat/high sugar “western” diet.  Metabolic pathways in the microbiome were changed and the microbiome gene expression was altered.  Rapid rise in inflammatory bowel diseases (IBD) might be related to western-style diet as bile composition can be altered by dietary fat, leading to increased growth if pro-inflammatory gut microbes.[16]  Increased intestinal permeability can be caused by frequent consumption of synthetic surfactant food additives (emulsifiers).  The same surfactants are added to foods as to pharmaceutics as absorption enhancers.  This might be an important fact to increasing incidence of e.g. CD.[17]  Inflammation Alters the Microbiota, Diet and Innate Immunity.

MUCOSAL Inflammation and E. coli

In CD subjects, adherent-invasive Escherichia coli (AIEC) pathovar has been identified in the mucosa.  According to Darfeuille-Michaud et al[18], AIEC strains are associated with CD, especially with the ileal-mucosa.  According to Ryan et al[19] E. coli DNA was found in 12/15 cases of CD but in 1/10 in controls, revealing DNA from E. coli is increased in the granulomas of CD subjects. It seems that adherent invasive E. coli have a role in early onset of the disease according to Sepehri et al[20].  Lymphoid follicles are the initial sites of inflammation in CD.[21],[22]  Findings (in vitro) revealed that enteropathogenic E. coli (EPEC) was capable of translocate across the M cell model, being regulated by the type III secretion system, but without detection of the bacterial effector.[23]  According to Chassaing et al[24] the AIEC bacteria targets the follicle-associated epithelium and can affect the Payer’s patches involving (at least) one virulence factor in addition to type 1 fimbriae (long polar fimbriae- LPF).

DIET and Effect on Bacterial Translocation Across Intestinal Epithelium

Ingested soluble plant fibres can block bacterial recruitment to the intestinal lining and there is a hypothesis for using plantain fibres as a therapeutic tool for CD.  The soluble plantain non-starch polysaccharide seems to inhibit the agglutination and adhesion of all adherent E. coli according to Martin et al[25].  In a study by Roberts et al[26] soluble plant fibres like plantain and broccoli reduces translocation of E. coli across M-cells but the emulsifier Polysorbate-80 has the opposite effect.  Not all NSP have the same effect upon AIEC translocation, i.e. NSP from leek and apple had little effect.

INNATE & Adaptive Immunity and Gene Associations

It is implied by gene associations in CD pathogenesis, that the gut micro flora plays important part and confirmed CD susceptibility loci are 71 upwards.[27]  Processing of phagocytosed bacteria and defects in autophagy are an emerging theme from molecular genetic studies of CD as well as other specific components within adaptive and innate immune pathways, which are highlighted too.[28]

EXISTING Therapeutic Approaches to Treatment of CD 

In 1932 Crohn et al[29] words were “medical therapy is purely palliative and supportive…but in general the proper approach to complete cure is by surgical reaction..” but new biological therapies and immunomodulatory agents are becoming recognized.

NEW Theraputic Approaches to Treatment of CD 

Treatments targeting the fundamental pathology involved are needed!  There is evidence on dysbiosis of mucosa-associated mocrobiota, in monozygotic twins with ileal-CD distinct from colonic-CD, an emergent biomarker candidate for customized treatment of CD.[30]

ANTIBIOTICS

In a meta-analysis of controlled clinical trials by Rahimi et al[31] results support the use of broad-spectrum antibacterial drugs as it improved clinical outcomes in CD subjects.  Subramanian et al[32] reveals effective killing of AIEC replicates, within the host’s macrophages, using combination antibiotics.

HYDROXYCLOROQUINE Increases Phagolysosomal pH and Improves Killing of Crohn´s E. coli

Hydoxychloroquine in treatment for CD alters phagolysosomal pH (AIEC requires acidic pH to replicate) and cellular iron mobilization, as well as enhances the efficacy of antibiotics and macrophage killing of other intra-macrophage organisms such as Coxiella burnetti and Tropheryma spp.[33],[34]

VITAMIN D Deficiency in CD

Low levels of vitamin D are associated with IBD, especially CD,[35],[36],[37],[38] and prevalence increases with increasing latitude.[39]  A novel vitamin D bioavailability test was used in a study by Farray et al[40] reveling that vitamin D2 absorption in CD subjects is unpredictable and about 30% less than in healthy controls.  In this study, more than 70% of the CD subjects were either vitamin D deficient or presented insufficient levels.  When vitamin D3 (1200 IU) was given orally to CD subjects, it significantly raced serum levels (mean 69 nmol/L to mean 96 nmol/L), but insignificantly reduced relapsing risk (from 29% to 13%).[41] Vitamin D has important role in effective immune response and there is clinical evidence for vitamin D as an immuneomodulator in IBD.[42],[43],[44]

VITAMIN D and Bacterial Killing in CD

There is strong evidence revealing vitamin D preventing infection by stimulating immunity by enhancing bacterial killing.  Vitamin D also modulates adaptive immunity, which lowers the risk of inflammation and autoimmune disease.[45]

NEW Treatment Strategies Targeting Macrophages Function in CD

Macrophage function is enhanced by vitamin D supplementation.  Flanagan et al[46] reveals findings on macrophage killing of E. coli in CD subjects, therefore further supports vitamin D supplementation as a therapeutic tool in cases of CD.

CONCLUSION

The role of the microbiota is important, especially for the immune system and as prophylactic tool against IBD like CD.  New therapeutic approaches to treatment of CD look promising, especially as most of them are far less invasive than surgery or medication.

Copyright @ Jörth 2008-2017

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