Michela Barichella1, Marco Severgnini2, Roberto Cilia1, Erica Cassani1, Carlotta Bolliri1, Serena Caronni1, Valentina Ferri1, Raffaella Cancello3, Camilla Ceccarani2,4, Samanta Faierman1, Giovanna Pinelli1,5, Gianluca De Bellis2, Luigi Zecca2,6, Emanuele Cereda7, Clarissa Consolandi2, Gianni Pezzoli1. 1. Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini-CTO, Milan, Italy. 2. Institute of Biomedical Technologies (IBT), Italian National Research Council (CNR), Milan, Italy. 3. IRCCS Istituto Auxologico Italiano, Obesity Research Laboratory, Milan, Italy. 4. Department of Health Sciences, San Paolo Hospital Medical School, University of Milan, Milan, Italy. 5. Department of Parkinson Disease Rehabilitation, Moriggia-Pelascini Hospital, Gravedona ed Uniti, Fondazione Europea Ricerca Biomedica (FERB), Gravedona, Italy. 6. Department of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, New York, NY USA. 7. Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Abstract
BACKGROUND: Although several studies have suggested that abnormalities in gut microbiota may play a critical role in the pathogenesis of PD, data are still extremely heterogeneous. METHODS: 16S gene ribosomal RNA sequencing was performed on fecal samples of 350 individuals, subdivided into idiopathic PD (n = 193, of whom 39 were drug naïve) stratified by disease duration, PSP (n = 22), MSA (n = 22), and healthy controls (HC; n = 113). Several confounders were taken into account, including dietary habits. RESULTS: Despite the fact that unadjusted comparison of PD and HC showed several differences in relative taxa abundances, the significant results were greatly reduced after adjusting for confounders. Although most of these differences were associated with disease duration, lower abundance in Lachnospiraceae was the only difference between de novo PD and HC (remaining lower across almost all PD duration strata). Decreased Lachnospiraceae and increased Lactobacillaceae and Christensenellaceae were associated with a worse clinical profile, including higher frequencies of cognitive impairment, gait disturbances, and postural instability. When compared with HC, MSA and PSP patients shared the changes in PD, with a few exceptions: in MSA, Lachnospiraceae were not lower, and Prevotellaceae were reduced; in PSP, Lactobacillaceae were similar, and Streptococcaceae were reduced. CONCLUSIONS: Gut microbiota may be an environmental modulator of the pathogenesis of PD and contribute to the interindividual variability of clinical features. Data are influenced by PD duration and several confounders that need to be taken into account in future studies. Prospective studies in de novo PD patients are needed to elucidate the net effect of dysbiosis on the progression of the disease.
BACKGROUND: Although several studies have suggested that abnormalities in gut microbiota may play a critical role in the pathogenesis of PD, data are still extremely heterogeneous. METHODS: 16S gene ribosomal RNA sequencing was performed on fecal samples of 350 individuals, subdivided into idiopathic PD (n = 193, of whom 39 were drug naïve) stratified by disease duration, PSP (n = 22), MSA (n = 22), and healthy controls (HC; n = 113). Several confounders were taken into account, including dietary habits. RESULTS: Despite the fact that unadjusted comparison of PD and HC showed several differences in relative taxa abundances, the significant results were greatly reduced after adjusting for confounders. Although most of these differences were associated with disease duration, lower abundance in Lachnospiraceae was the only difference between de novo PD and HC (remaining lower across almost all PD duration strata). Decreased Lachnospiraceae and increased Lactobacillaceae and Christensenellaceae were associated with a worse clinical profile, including higher frequencies of cognitive impairment, gait disturbances, and postural instability. When compared with HC, MSA and PSPpatients shared the changes in PD, with a few exceptions: in MSA, Lachnospiraceae were not lower, and Prevotellaceae were reduced; in PSP, Lactobacillaceae were similar, and Streptococcaceae were reduced. CONCLUSIONS: Gut microbiota may be an environmental modulator of the pathogenesis of PD and contribute to the interindividual variability of clinical features. Data are influenced by PD duration and several confounders that need to be taken into account in future studies. Prospective studies in de novo PDpatients are needed to elucidate the net effect of dysbiosis on the progression of the disease.
Authors: Zachary D Wallen; Mary Appah; Marissa N Dean; Cheryl L Sesler; Stewart A Factor; Eric Molho; Cyrus P Zabetian; David G Standaert; Haydeh Payami Journal: NPJ Parkinsons Dis Date: 2020-06-12
Authors: Aubrey M Schonhoff; Gregory P Williams; Zachary D Wallen; David G Standaert; Ashley S Harms Journal: Prog Brain Res Date: 2019-12-05 Impact factor: 2.453
Authors: Michal Lubomski; Xiangnan Xu; Jean Y H Yang; Carolyn M Sue; Ryan L Davis; Andrew J Holmes Journal: J Neurol Date: 2021-06-15 Impact factor: 6.682
Authors: Line Friis Bakmann Christensen; Saeid Hadi Alijanvand; Michał Burdukiewicz; Florian-Alexander Herbst; Henrik Kjeldal; Morten Simonsen Dueholm; Daniel E Otzen Journal: Protein Sci Date: 2021-06-09 Impact factor: 6.993