Topics at the IHMC 2015 meeting in Luxembourg were wide-ranging. Here are some highlights of particular interest:
Pettersson talked about possible compartmentalization of microbe-host interactions. He noted that keeping microbes within the boundaries in which they are compartmentalized is an energy-saving process. The stressed immune system consumes energy, and if the microbiome is involved in metabolism, it could work on energy sparing and energy saving for organs such as the brain.
For a review on metabolic interactions between host and gut microbiota, see this article in Science.
Versalovic talked about microbiome shifts over the life span, with diet playing a key role. Actinobacteria are dominant early and fade later. With ageing, there is a shift from Firmicutes to Bacteroidetes, with Firmicutes becoming possibly more important in later life. In children under 12, researchers observe more Firmicutes and Actinobacteria than in young adults. Versalovic says gut microbes actively metabolize and synthesize active molecules. Oxidative phosphorylation and lipopolysaccharide (LPS) biosynthesis may also link with age and “inflammageing”.
Bercik says functional MRI in humans receiving probiotics shows changes in brain regional activity (Tillisch, 2013). Bacteria can act via cytokine modulation, via secreted molecules, or via afferent nerve cell excitation. Most data so far are from animal studies.
Previous results show germ-free mice are more exploratory, less anxious, with lower expression of nerve growth factor. Multiple genes are up- or down-regulated, some related to neuron plasticity and connectivity. Bercik’s work at McMaster is replicating the link between germ-free status and lesser anxiety. Similar results are found with mice monocolonized with with an E. coli strain. Trichuris muris parasite induces infection with increased anxiety in mice. Treatment with the probiotic B. longum restores normal behavior in a non-immune-mediated way. Different probiotic treatments may work in different ways. Some probiotics change host gene expression in a fairly short time frame.
In unpublished research, de Palma found conventional but not germ-free maternally-separated mice display anxiety-like behavior; this is associated with an impaired HPA [hypothalamic-pituitary-adrenal] axis and altered cholinergic gut innervations. Conventional mice co-housed with a healthy donor mouse were different from those co-housed with a maternally-separated mouse: the effects of maternal separation on the microbiota led to differences in the metabolome, including neuroactive glutamate, tryptophan and more. The overall conclusion is that both host factors and microbiota factors need be combined for phenotype.
In another line of study, researchers transferred fecal microbiota from healthy and IBS donors to ten mice each. IBS-D [IBS associated with diarrhea] microbiota induces immune activation, mainly the elevated expression of innate immunity genes. Beta-defensins were increased in some mice, with marked heterogeneity. IBS mice had increased paracellular permeability and positive ion transport. Metabolomic profiles were very different. DePalma says there are multiple pathways for gut-brain activation and it is important to consider psychiatric/psychological parameters in selection of donors for FMT.
Hugenholtz talked about COPD, a permanent degenerative disease which stems from inhalation of fumes and pollutants. He showed that fecal transplant can ameliorate COPD in a mouse model. Mice with COPD receiving a fecal transplant showed reduction of inflammatory markers and a drastic shift in microbiota composition.
See the GMFH summary of the IHMC plenary sessions here.
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