Komagataella pastoris KM71H Mitigates Depressive-Like Phenotype, Preserving Intestinal Barrier Integrity and Modulating the Gut Microbiota in Mice

• Published in: Molecular neurobiology 2023-07, Vol.60 (7), p.4017-4029
• Main Authors: Birmann, Paloma T., Casaril, Angela M., Pesarico, Ana Paula, Rodrigues, Rafael R., Conceição, Fabricio R., Sousa, Fernanda Severo Sabedra, Collares, Tiago, Seixas, Fabiana K., Savegnago, Lucielli
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Antidepressants; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cell Biology; Clindamycin; Depressive Disorder, Major; Dysbacteriosis; Gastrointestinal Microbiome; Grooming; Hippocampus; Immunoglobulins; Intestinal microflora; Komagataella pastoris; Male; Mice; Microbiota; mRNA; Neurobiology; Neurology; Neurosciences; Phenotypes; Probiotics; Small intestine; Toll-like receptors; Zonula occludens-1 protein
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-023-03326-7

The role of intestinal microbiota in the genesis of mental health has received considerable attention in recent years, given that probiotics are considered promising therapeutic agents against major depressive disorder. Komagataella pastoris KM71H is a yeast with probiotic properties and antidepressant-like effects in animal models of depression. Hence, we evaluated the antidepressant-like effects of K. pastoris KM71H in a model of antibiotic-induced intestinal dysbiosis in male Swiss mice. The mice received clindamycin (200 μg, intraperitoneal) and, after 24 h, were treated with K. pastoris KM71H at a dose of 8 log CFU/animal by intragastric administration (ig) or PBS (vehicle, ig) for 14 consecutive days. Afterward, the animals were subjected to behavioral tests and biochemical analyses. Our results showed that K. pastoris KM71H administration decreased the immobility time in the tail suspension test and increased grooming activity duration in the splash test in antibiotic-treated mice, thereby characterizing its antidepressant-like effect. We observed that these effects of K. pastoris KM71H were accompanied by the modulation of the intestinal microbiota, preservation of intestinal barrier integrity, and restoration of the mRNA levels of occludin, zonula occludens-1, zonula occludens-2, and toll-like receptor-4 in the small intestine, and interleukin-1β in the hippocampi of mice. Our findings provide solid evidence to support the development of K. pastoris KM71H as a new probiotic with antidepressant-like effects.