The role of the intestinal microbiome in cognitive decline in patients with kidney disease
Carsten A. Wagner, Isabelle Frey‐Wagner, Alberto Ortíz, Robert J. Unwin, Sophie Liabeuf, Yoko Suzumoto, Anna Iervolino, Alessandra Stasi, Vincenzo Di Marzo, Loreto Gesualdo, Ziad A. Massy, CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target) collaborators, Giovambattista Capasso, Alexandre Andrade, Mustafa Arıcı, Maie Bachmann, Matthew A. Bailey, Michelangela Barbieri, Mickaël Bobot, Annette Bruchfeld, Inga Arune-Bumblyte, Daiva Rastenytė, Antonello Calcutta, Giovanna Capolongo, Sol Carriazo, Michele Ceccarelli, Adrian Covic, Ananya De, Pilar Delgado, Nicole Endlich, Matthias Endres, Fabrizio Esposito, Michele Farisco, Quentin Faucher, Ana Carina Ferreira, Andreja Figurek, Denis Fouque, Casper Franssen, Ivo Fridolin, Sebastian Frische, Liliana Gârneaţă, Loreto Gesualdo, Konstantinos Giannakou, Olivier Godefroy, Aleksandra Golenia, Dimitrios Goumenos, Eugenio Gutiérrez Jiménez, Gaye Hafez, Ewout J. Hoorn, Pedro Henrique Imenez Silva, Raafiah Izhar, Dearbhla Kelly, Shelli R. Kesler, Aleksandra Klimkowicz‐Mrowiec, Samuel Knauß, Justina Kurganaite, Hélène Levassort, Sophie Liabeuf, Jolanta Małyszko, Laila-Yasmin Mani, Gianvito Martino, Ziad A. Massy, Christopher Mayer, Armida Mucci, Alma Mutevelić-Turković, Rikke Nielsen, Dorothea Nitsch, Alberto Ortiz, Vasileios Panagiotopoulos, Despoina Karasavvidou, Giuseppe Paolisso, Bojana Pejušković, Marion Pépin, Alessandra Perna, Andrea Perrottelli, Vesna Pešić, Pasquale Pezzella, Merita Rroji, Ivan Rychlík, Giorgos K. Sakkas, Mariadelina Simeoni, María José Soler Romeo, Goce Spasovski, Ana Starčević, Gioacchino Tedeschi, Francesco Trevisani, Robert Unwin, Evgueniy Vazelov, Carsten A. Wagner, Franca Wagner, Christoph Wanner, Andrzej Więcek, Hong Xu, Miriam Zacchia, Lefteris Zacharia, Irene Zecchino, Carmine Zoccali, Francesco Mattace‐Raso, Karlhans Endlich, Norberto Perico
Abstract
Cognitive decline is frequently seen in patients with chronic kidney disease (CKD). The causes of cognitive decline in these patients are likely to be multifactorial, including vascular disease, uraemic toxins, blood-brain barrier leakage, and metabolic and endocrine changes. Gut dysbiosis is common in patients with CKD and contributes to the increase in uraemic toxins. However, the gut microbiome modulates local and systemic levels of several metabolites such as short-chain fatty acids or derivatives of tryptophan metabolism, neurotransmitters, endocannabinoid-like mediators, bile acids, hormones such as glucagon-like peptide 1 (GLP1) or cholecystokinin (CCK). These factors can affect gut function, immunity, autonomic nervous system activity and various aspects of brain function. Key areas include blood-brain barrier integrity, nerve myelination and survival/proliferation, appetite, metabolism and thermoregulation, mood, anxiety and depression, stress and local inflammation. Alterations in the composition of the gut microbiota and the production of biologically active metabolites in patients with CKD are well documented and are favoured by low-fiber diets, elevated urea levels, sedentary lifestyles, slow stool transit times and polypharmacy. In turn, dysbiosis can modulate brain function and cognitive processes, as discussed in this review. Thus, the gut microbiome may contribute to alterations in cognition in patients with CKD and may be a target for therapeutic interventions using diet, prebiotics and probiotics.