Multiomics analysis of the metabolome and microbiota in a rat model of cerebral amyloidosis

CAMPANELLI, L; GALEANO P; GONZALEZ-JIMENEZ, A; RODRÍGUEZ DE FONSECA, FERNANDO; CUELLO, A CLAUDIO; CASTAÑO EM; MORELLI LAURA

Porto

Congreso; ISN-ASN Meeting 2023; 2023

ISN

Emerging literature indicates that gut microbiotacould impact on the development of different pathologies including Alzheimer'sdisease (AD), the leading cause of dementia in older adults. The intestinalmicrobiota is a complex ecosystem composed mainly from bacteria of the phyla Bacteroidetes and Firmicutesof which some are considered pathogenic while most of them are involved in homeostaticprocesses promoting beneficial health effects. Evidence using animal modelsindicates that the gut microbiota can communicate with the central nervous system(CNS), influencing brain function and behavior. However, the mechanisms bywhich microbiota may impact and generate an effect on AD have not beenelucidated.Here we studied microbiota and metabolome of McGill-R-Thy1-APPrats, a transgenic (Tg) model of early stages of AD-like amyloid pathology. Brains,stool and plasma samples were collected from 9 month-old male control (Wistar)(n=20) and Tg rats (n=23). Fecal samples were split in 2 and one part (n=43)was sent to StarSEQ GmbH (Germany) for 16S microbial rDNA genotyping using the16S platform (Illumina) and the other one (n=30) with plasma samples to Metabolon (USA) for untargetedUPLC/MS-MS metabolomics to characterize the fecal and plasma metabolome. Weobtained information on 189 OTUs, 702 metabolites in feces and 686 in plasma.Together, these data were curated and analyzed using the R packages: mixOmics,Metaboanalyst and Fella to define the type of microbe and thesecreted compound that best discriminates Tg rats. On an exploratory basis, presenceof Turicibacter and Lactobacillus (phylum Firmicutes) andlack of Gastranaerophilales (phylum Melainabacteria),Paraprevotella and Alloprevotella (phylum Bacteroidetes) in Tg ratswere observed. We explored the correlations (r > 0.80) of this OTUs and ratsmetabolome and identified more than 10 metabolites which in turn are associatedwith the pathways of fatty acid metabolism and ketone bodies. This workrepresents a first step towards understanding the association of peripheralinputs (gut microbiota and the intestinal metabolome) on neurodegeneration, atopic of which very little is known to date. @font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073697537 9 0 511 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-font-kerning:0pt;mso-ligatures:none;mso-ansi-language:UZ-CYR;mso-fareast-language:EN-US;}div.WordSection1{page:WordSection1;}