Marina Mora Ortiz

MEMOIR project

Marina Mora Ortiz develops her research project within the group GC09 Nutrigenomics – Metabolic Syndrome, under the supervision of Prof. José López-Miranda. Her project is titled MEMOIRMEtagenomic Modelling of cOgnitive ImpaiRment. It aims to determine the effect of diet and/or a probiotic treatment on the gut-microbiota and its association with Mild Cognitive Impairment. Marina’s project will last from February 2021 till January 2024.

Mild Cognitive Impairment (MCI) is a syndrome that encompasses decline in some mental abilities including memory, perception and language domains. It has been hypothesised that the syndrome may be triggered by intestinal dysfunction. In fact, the microbial-gut-brain axis, a feedback mechanism between the gut microbiota and the central nervous system, has been previously associated with senescence and neuropsychiatric diseases. Our project aims to determine the effect of diet and/or a probiotic treatment on the gut-microbiota and its association with MCI. Existing faecal samples (from 50 individuals over age 65) available at IMIBIC, will be used to define gut microbiota genes linked to MCI.

The high-throughput analysis of genetic material from the gut microbiota, i.e. gut microbiota shotgun metagenomics, will be employed to sequence existing faecal material available at IMIBIC. Statistical modelling, e.g. Linear Mixed Effect Models (LMEM), Orthogonal Projection on the Latent Structure Discriminant Analysis (O-PLS DA) and Permanova amongst others, will be used to address the three main objectives of these study, which are: i) to identify the effects of a probiotic treatment on the MCI, ii) to determine the effect of the dietary intervention (Mediterranean diet) on the cognitive state of the individuals and finally, iii) to investigate any sex association to the interventions. The project will also involve training in shotgun metagenomics and bioinformatics. The final outcome could elucidate if dietary interventions and probiotics can palliate MCI.

The aim of this project is to study the association between gut metagenome and MCI and its effect on deleterious changes in human cognition. The project also aims to investigate potential mechanisms to revert MCI, through the use of dietary intervention and probiotic treatments. This will provide evidence of the direction of causation and identify microbial targets for human clinical interventions to reduce MCI during ageing. Our hypothesis is that MCI-associated gut metagenome negatively affects the gut-brain-axis and consequently human mental health.

Objective 1 is to identify gut microbiota genes associated with MCI. Shotgun metagenomics analyses will be carried out in stool samples from an existing cohort (n=50) available at the host group by sequencing in an Illumina MiSeq platform. Using both, Linear Mixed Effect Models (LMEM) and Orthogonal Projection on the Latent Structure Discriminant Analysis (O-PLS DA), we would identify genes associated with MCI in the cohort.

Objective 2 is to test the effects of the combined intervention of a Mediterranean diet (it will contain 35-38% of calories in the form of fat (22% monounsaturated fat, 6% polyunsaturated fat, 7% saturated fat), 15% protein and 50% carbohydrates) and a probiotic with 109 CFU of Lactobacillus rhamnosus and Bifidobacterium longum (Biopolis-MIX42 capsules) in the modulation of gut metagenome in association with MCI.

Objective 3 aims to analyse the relationship between gut metagenome, the factors discussed in Obj. 1 and Obj. 2, and sex. This would enable a personalised clinical approach towards MCI clinical treatment strategies and further study designs.