Salivary bacterial signatures in depression-obesity comorbidity are associated with neurotransmitters and neuroactive dipeptides

Abstract

Background Depression and obesity are highly prevalent, often co-occurring conditions marked by inflammation. Microbiome perturbations are implicated in obesity-inflammation-depression interrelationships, but how the microbiome mechanistically contributes to pathology remains unclear. Metabolomic investigations into microbial neuroactive metabolites may offer mechanistic insights into host-microbe interactions. Using 16S sequencing and untargeted mass spectrometry of saliva, and blood monocyte inflammation regulation assays, we identified key microbes, metabolites and host inflammation in association with depressive symptomatology, obesity, and depressive symptomatology-obesity comorbidity. Results Gram-negative bacteria with inflammation potential were enriched relative to Gram-positive bacteria in comorbid obesity-depression, supporting the inflammation-oral microbiome link in obesity-depression interrelationships. Oral microbiome was more highly predictive of depressive symptomatology-obesity co-occurrences than of obesity or depressive symptomatology independently, suggesting specific microbial signatures associated with obesity-depression co-occurrences. Mass spectrometry analysis revealed significant changes in levels of signaling molecules of microbiota, microbial or dietary derived signaling peptides and aromatic amino acids among depressive symptomatology, obesity and comorbid obesity-depression. Furthermore, integration of the microbiome and metabolomics data revealed that key oral microbes, many previously shown to have neuroactive potential, co-occurred with potential neuropeptides and biosynthetic precursors of the neurotransmitters dopamine, epinephrine and serotonin. Conclusions Together, our findings offer novel insights into oral microbial-brain connection and potential neuroactive metabolites involved.

Analysis of 16S rRNA Gene Sequence of Nasopharyngeal Exudate Reveals Changes in Key Microbial Communities Associated with Aging

“…In recent years, solid evidence has been collected to support the idea that the microbial communities that inhabit the different anatomical areas of the human body could play a key role in these processes, and there has been much speculation about possible medical interventions [ 1 , 2 , 3 , 4 , 5 , 6 ]. Although most research has focused on the well-studied gut microbiome, there is growing evidence that variations in microbial communities in other sites of the body are also responsible for wide-ranging health effects [ 7 , 8 , 9 , 10 , 11 ]. The case of the respiratory tract is curious, since the lungs were long believed to be sterile, despite the fact that they are constantly exposed to microorganisms in inhaled air and the upper respiratory tract [ 12 ], which has been the main cause that the respiratory microbiome has barely been studied until very recently [ 13 ].…”

Critical Factors in Sample Collection and Preparation for Clinical Metabolomics of Underexplored Biological Specimens

“…The preparation of saliva samples for metabolomics analysis is quite simple. In general, the procedures involve protein precipitation with acetonitrile [ 189 , 190 , 191 , 192 , 193 , 194 , 195 ], methanol [ 196 , 197 , 198 ], or a combination of methanol/acetonitrile (1:1, v / v ) [ 199 , 200 , 201 ], methanol/water [ 202 , 203 , 204 , 205 , 206 ], and methanol/acetonitrile/water (2:2:1, v / v / v ) [ 207 ]. Other studies have used isopropanol [ 208 ] or acetone [ 209 ], which requires evaporation and resuspension in an appropriate solvent before chromatographic analysis.…”

Neuromicrobiology, an emerging neurometabolic facet of the gut microbiome?

“…and Tannerella spp. co-occurred with tryptophan biosynthesis and contained genes for tryptophan biosynthetic pathways ( Kaur et al, 2019 ; Valles-Colomer et al, 2019 ; Aleti et al, 2022 ). Generally, five enzymes encoded by seven genes ( trpA-F ), typically arranged in a single cluster, are involved in tryptophan biosynthesis in microbes ( Crawford, 1989 ).…”