Gut Microbiome Alteration after Reboxetine Administration in Type-1 Diabetic Rats

Abstract

Antidepressants are drugs commonly used in clinical settings. However, there are very limited studies on the effects of these drugs on the gut microbiota. Herein, we evaluated the effect of reboxetine (RBX), a selective norepinephrine (noradrenaline) reuptake inhibitor (NRI), on gut microbiota in both diabetic and non-diabetic rats. This is the first report of relation between reboxetine use and the gut microbiota to our knowledge. In this study, type-1 diabetes induced by using streptozotocin (STZ) and RBX was administered to diabetic rats and healthy controls for 14 days. At the end of the treatment, stool samples were collected. Following DNA extraction, amplicon libraries for the V3-V4 region were prepared and sequenced with the Illumina Miseq platform. QIIME was used for preprocessing and analysis of the data. As a result, RBX had a significant effect on gut microbiota structure and composition in diabetic and healthy rats. For example, RBX exposure had a pronounced microbial signature in both groups, with a low Firmicutes/Bacteroidetes ratio and low Lactobacillus levels. While another abundance phylum after exposure to RBX was Proteabacteria, other notable taxa in the diabetic group included Flavobacterium, Desulfovibrionaceae, Helicobacteriaceae, Campylobacterales, and Pasteurellacae when compared to the untreated group.

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“…Lactobacillus genus represents a common probiotic, but this protective effect may depend on the presence of other intestinal bacteria and work together in a complementary manner ( 49 ). Most other studies have reported that Lactobacillus was found in higher abundance in control groups than in diabetic groups ( 50 , 51 ). But here, the abundance of Lactobacillus being significantly higher in the DCM group than in the CON group.…”

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“…However, RBX treatment significantly affected beta diversity in healthy and diabetic rates compared to the control. Relative taxa analysis reveals that RBX treatment reduced Firmicutes but increased Bacteroides, and Proteobacteria phyla (Aydin et al, 2021). In terms of families, Prevotellaceae increased, but Lactobacillaceae and Clostridiaceae decreased.…”

“…In terms of families, Prevotellaceae increased, but Lactobacillaceae and Clostridiaceae decreased. Random forest analysis, this is a technique that assigns OTU's, and is a form of metagenomic sequencing that uses the 16sribosomal RNA to identify species in a particular sample, and fecal samples were analyzed in this study (Aydin et al, 2021). There was a total of 3782 OTU's identified even though there was not any significant difference on the species level there was a significant difference in diversity within the microbiome (Aydin et al, 2021).…”

“…Random forest analysis, this is a technique that assigns OTU's, and is a form of metagenomic sequencing that uses the 16sribosomal RNA to identify species in a particular sample, and fecal samples were analyzed in this study (Aydin et al, 2021). There was a total of 3782 OTU's identified even though there was not any significant difference on the species level there was a significant difference in diversity within the microbiome (Aydin et al, 2021). Unifrac analysis was able to identify the differences in the colonies found but was unable to identify the differences between which species were more commonly found in diabetic rats vs. the control rats when treated with RBX.…”

Rebokseti̇n’i̇n Di̇yabeti̇k Siçanlarda Bozulmuş Davraniş Parametreleri̇ Üzeri̇ndeki̇ Yararli Etki̇leri̇

“…Reboksetin duygudurum, dikkat, öğrenme ve bellek fonksiyonlarında kritik rol oynadığı bilinen bir nörotransmitter olan noradrenalin'in santral nörotransmisyonunu artırarak gerek emosyon gerekse kognisyon üzerine olumlu etkiler gösterdiği bilinen antidepresan bir ilaçtır [18][19][20][21][22]. Literatürde reboksetin'in diyabetik deneklerde plazma glukoz seviyeleri, nöropatik ağrı parametreleri ve barsak mikrobiyomu üzerine etkilerinin araştırıldığı bazı çalışmalar bulunmakla birlikte, bu antidepresanın diyabete bağlı olarak gelişen depresyon, anksiyete ve öğrenme/bellek zayıflıkları üzerine etkileri daha önce araştırılmamıştır [23][24][25]. Bu nedenle bu çalışmada, reboksetin'in, deney hayvanlarında diyabet ile indüklenen emosyonel ve bilişsel bozukluklar üzerine farmakolojik etkilerinin araştırılması amaçlanmıştır.…”