The influence of fungal microbiota and iron therapies in inflammatory bowel disease’s gut environment

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The occurrence of inflammatory bowel disease (IBD) -ulcerative colitis (UC) and Crohn’s disease (CD)- is increasing worldwide, yet the reasons remain unknown. It is characterized by the perpetuation of intestinal inflammation, and intestinal dysbiosis and decreased complexity of the gut microbiota ecosystem may contribute to this. Recent research has focused on the potential role of the bacterial intestinal microbiota in IBD pathogenesis. However, the fungal microbiota has been poorly studied. A recent study, led by French researchers from the Saint Antoine Hospital in Paris, showed that besides bacterial dysbiosis, fungal microbiota dysbiosis might play a role in IBD pathogenesis. Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects was determined. Besides altered bacterial microbiota biodiversity and composition, the researchers found that fungal microbiota diversity was skewed in IBD patients, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with healthy subjects. Card9 gene had a central role in host-fungi interactions, as reported previously in other studies. Besides, fungi growing at the expense of bacteria characterized Crohn’s gut microbiota. IBD microbiota showed specific bacteria-fungi correlation pattern, with a higher number of significant correlations in UC compared with healthy subjects. There was a homogeneous correlation network in healthy subjects, whereas CD and UC networks were dramatically different. These data suggest a complex relationship between the bacteria and fungi in the gut microbiota, which is linked to disease-specific inter-kingdom alterations.

 

Although a critical role of gut microbial dysbiosis in IBD pathogenesis is assumed, little is known with regard to how environmental factors promote changes in the gut microbial ecosystem. A recent open-labelled clinical trial, led by Dr Dirk Haller from the Technical University Munich, studied the impact of oral versus intravenous iron replacement therapy (IRT) on the gut microbiota and metabolome in patients with IBD. The study population included three groups of iron-deficient participants: patients with CD, UC and control subjects without gastrointestinal disorders. Participants were randomised into the oral or intravenous IRT group and were followed up for 3 months from the initiation of IRT. Serum and faecal samples were collected at baseline and after the end of intervention. IBD was associated with specific faecal microbiota and metabolome fingerprints. Both IBD groups showed marked interindividual differences in their faecal bacterial communities, whereas control participants represented a more homogeneous group of samples. Specifically, bacterial communities in patients with CD were most heterogeneous and distant from UC and control subjects. The effect of the disease on taxa richness was more pronounced in patients with CD, which were characterized by a significant drop in the relative abundance of Clostridiales from Firmicutes phylum. Metabolite analysis also showed separation of IBD patients from control anaemic participants. For instance, ceramide phosphate and several fatty acids signal intensities were higher in faeces from patients with CD, whereas patients with UC showed lower intensities of phospholipids. Furthermore, bacterial communities in IBD patients were more sensitive to overtime changes associated with IRT compared to control anaemic participants. However, the IRT-induced shifts in bacterial diversity and composition were not associated with changes in disease activity. Finally, oral iron administration differentially affects bacterial communities and their metabolites compared with intravenous therapy. After oral IRT, there were differences at the level of both metabolome and the occurrence of specific bacterial phylotypes. These changes included higher signals for cholesterol, palmitate and phosphatidylglycerol metabolites together with a decreased in the relative abundance of Collinsella aerofaciens, Faecalibacterium prausnitzii, Ruminococcus bromii and Dorea sp.

 

In conclusion, both bacterial and fungal microbiota biodiversity and composition are altered in IBD patients, thus it may play a role in IBD pathogenesis. Besides, oral and intravenous iron therapies differentially affect the gut microbiota and metabolome in patients with IBD.

 

 

References:

Sokol H, Leducq V, Aschard H, et al. Fungal microbiota dysbiosis in IBD. Gut. 2016; doi: 10.1136/gutjnl-2015-310746.

Lee T, Clavel T, Smirnov K, et al. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut. 2016; doi: 10.1136/gutjnl-2015-309940.

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados