Effect of long-term methylene blue treatment on the composition of mouse gut microbiome and its relationship with the cognitive abilities of mice

Abstract

In recent years, methylene blue (MB) has attracted considerable interest as a potential drug for the treatment of methemoglobinemia and neurodegenerative diseases. MB is active against microorganisms from various taxonomic groups. However, no studies have yet been conducted on the effect of MB on the intestinal microbiome of model animals. The aim of this work was to study the effect of different concentrations of MB on the mouse gut microbiome and its relationship with the cognitive abilities of mice. We showed that a low MB concentration (15 mg/kg/day) did not cause significant changes in the microbiome composition. The Bacteroidetes/Firmicutes ratio decreased relative to the control on the 2nd and 3rd weeks. A slight decrease in the levels Actinobacteria was detected on the 3rd week of the experiment. Changes in the content of Delta, Gamma, and Epsilonproteobacteria have been also observed. We did not find significant alterations in the composition of intestinal microbiome, which could be an indication of the development of dysbiosis or other gut dysfunction. At the same time, a high concentration of MB (50 mg/kg/day) led to pronounced changes, primarily an increase in the levels of Delta, Gamma and Epsilonproteobacteria. Over 4 weeks of therapy, the treatment with high MB concentration has led to an increase in the median content of Proteobacteria to 7.49% vs. 1.61% in the control group. Finally, we found that MB at a concentration of 15 mg/kg/day improved the cognitive abilities of mice, while negative correlation between the content of Deferribacteres and cognitive parameters was revealed. Our data expand the understanding of the relationship between MB, cognitive abilities, and gut microbiome in respect to the antibacterial properties of MB.

Nrf2/ARE Activators Improve Memory in Aged Mice via Maintaining of Mitochondrial Quality Control of Brain and the Modulation of Gut Microbiome

“…Gut microbiome of MB-treated mice contained 11 genera with OTU of more than 0.02, while the control mice and RSV-treated mice contained 17 genera and DMF-treated mice contained 16 genera (Figure 11). Thus, these results and our previous data [27] show some evidence of MB-induced dysbiosis, but we cannot say that MB causes dysbiosis, since the other markers of dysbiosis are not observed. It is known that dysbiosis altered brain function and induced depressive-like behavior [86].…”

“…This implies the long-term treatment by drugs that are aimed at slowing down the processes of cognitive impairment, which can increase the degree of the effect of the drug on the intestinal composition of the microbiome. Recently, we found that treatment by a high concentration of MB (50 mg/kg/day) during one month induced dysbiosis, which manifested in an increase in Proteobacteria level [ 27 ]. Classically thought to be markers of dysbiosis in inflammatory bowel disease are increase in the Proteobacteria and Bacteroidetes phyla bacteria, decrease in the number of Firmicutes phylum bacteria, and decrease in the alpha-diversity index [ 84 ].…”

“…DMF and MB are not well understood in comparison with RSV. There are few studies of the effect of MB on the mouse gut microbiome [ 27 ] and DMF effect on the gut microbiota profile of patients with multiple sclerosis [ 28 ].…”

Cognitive function improvement after fecal microbiota transplantation in Alzheimer’s dementia patient: a case report

“…Bacteroidales, Bacteroidia, Tannerellaceae, and Actinobacteria were the more enriched taxonomy after FMT. These genera were reported to be associated with cognitive function (Figure 2(C)) [14][15][16] . Functional biomarker analysis using the Kruskal-Wallis H test was performed between the pre-and post-FMT groups by using EzBio-Cloud Apps (ChunLab Inc., Seoul, Korea).…”

Design, Synthesis, and Validation of a Novel [11C]Promethazine PET Probe for Imaging Abeta Using Autoradiography

“…Phenothiazine analogs have versatile applications across many diseases, including antimicrobial effects [ 24 , 25 , 26 ], antitumor effects [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ], and potential roles in the treatment of neurodegenerative disease [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. In the past, we showed PMZ binds to Abeta available in the brain lysate of 5XFAD mice in an in vitro study.…”