Bidirectional Microbiome-Gut-Brain-Axis Communication Influences Metabolic Switch-Associated Responses in the Mosquito Anopheles culicifacies

Abstract

The periodic ingestion of a protein-rich blood meal by adult female mosquitoes causes a drastic metabolic change in their innate physiological status, which is referred to as a ‘metabolic switch’. While understanding the neural circuits for host-seeking is modestly attended, how the gut ‘metabolic switch’ modulates brain functions, and resilience to physiological homeostasis, remains unexplored. Here, through a comparative brain RNA-Seq study, we demonstrate that the protein-rich diet induces the expression of brain transcripts related to mitochondrial function and energy metabolism, possibly causing a shift in the brain’s engagement to manage organismal homeostasis. A dynamic mRNA expression pattern of neuro-signaling and neuro-modulatory genes in both the gut and brain likely establishes an active gut–brain communication. The disruption of this communication through decapitation does not affect the modulation of the neuro-modulator receptor genes in the gut. In parallel, an unusual and paramount shift in the level of neurotransmitters (NTs), from the brain to the gut after blood feeding, further supports the idea of the gut’s ability to serve as a ‘second brain’. After blood-feeding, a moderate enrichment of the gut microbial population, and altered immunity in the gut of histamine receptor-silenced mosquitoes, provide initial evidence that the gut-microbiome plays a crucial role in gut–brain–axis communication. Finally, a comparative metagenomics evaluation of the gut microbiome highlighted that blood-feeding enriches the family members of the Morganellaceae and Pseudomonadaceae bacterial communities. The notable observation of a rapid proliferation of Pseudomonas bacterial sp. and tryptophan enrichment in the gut correlates with the suppression of appetite after blood-feeding. Additionally, altered NTs dynamics of naïve and aseptic mosquitoes provide further evidence that gut-endosymbionts are key modulators for the synthesis of major neuroactive molecules. Our data establish a new conceptual understanding of microbiome–gut–brain–axis communication in mosquitoes.

The buzz in the field: the interaction between viruses, mosquitoes, and metabolism

“…A blood meal taken by a female mosquito can induce a pronounced metabolic change in its physiological status (Figure 2A). This phenomena is known as a ' metabolic switch' (Das De et al, 2022). Das De et al compared the transcriptome of sugar-fed and blood-fed mosquitos using RNA-seq and showed that feeding blood (a high protein diet), induced expression of transcripts in the brain that are related to mitochondrial function and energy metabolism (Figure 2B) (Das De et al, 2022).…”

“…This phenomena is known as a ' metabolic switch' (Das De et al, 2022). Das De et al compared the transcriptome of sugar-fed and blood-fed mosquitos using RNA-seq and showed that feeding blood (a high protein diet), induced expression of transcripts in the brain that are related to mitochondrial function and energy metabolism (Figure 2B) (Das De et al, 2022). Blood meals can also serve as an indirect source for lipids.…”

“…Nutritional resources required for egg production by autogenous mosquitoes are fulfilled by gut microbiota of the mosquito (Coon et al, 2016) (B) Intake of a protein rich blood meal activates the 'metabolic switch' in female mosquitoes. Following a blood meal brain transcripts related to energy metabolism and mitochondrial function were observed to be increased (Das De et al, 2022). Gut microbiome plays a significant role in gut-brain-axis of communication (Das De et al, 2022) (C) Proteins and sugars ingested in a blood and/or a sugar meal are digested and transported to the fat body of the mosquito by lipophorins.…”

“…Following a blood meal brain transcripts related to energy metabolism and mitochondrial function were observed to be increased (Das De et al, 2022). Gut microbiome plays a significant role in gut-brain-axis of communication (Das De et al, 2022) (C) Proteins and sugars ingested in a blood and/or a sugar meal are digested and transported to the fat body of the mosquito by lipophorins. Yolk protein precursor-vitellogenin is produced using stored TAGs in the fat body.…”

Gut microbiota and derived metabolomic profiling in glaucoma with progressive neurodegeneration

“…The brain-gut axis has been well studied in these diseases, and it provides a bidirectional communication system between the central nervous system and the gastrointestinal tract via diverse signaling pathways, including energy metabolism, oxidative stress, mitochondrial function, and neuroinflammation. (Heintz-Buschart et al, 2018;Das De et al, 2022;Giridharan et al, 2022;Terkelsen et al, 2022) Given the similarities in the immune and neurodegenerative factors between glaucoma and Alzheimer's disease and Parkinson's disease, we speculate that microbial communication between the gastrointestinal tract and the eye is involved in the progressive neurodegeneration in glaucoma.…”