This issue of MeiG Guide broadcasts the latest research progress on metabolome for you!
Title: The metabolic overdrive hypothesis: hyperglycolysis and glutaminolysis in bipolar mania
Metabolic hyperdrive hypothesis: hyperglycolysis and glutamine breakdown in bipolar mania.
Authors: Iain H Campbell et al.
Time: 2024-01-25
Journal: Molecular Psychiatry
Impact factor: 11
doi：10.1038/s41380-024-02431-w
Summary:
Evidence from different research areas such as chronobiology, metabolomics, and magnetic resonance spectroscopy suggests that energy dysregulation is a central feature of the pathophysiology of bipolar disorder. This study proposes that mania represents a state of enhanced brain energy metabolism promoted by high glycolysis and glutamine breakdown. When oxidative glucose metabolism in the brain is impaired, neurons can use glutamate as a replacement substrate to produce energy through oxidative phosphorylation. Glycolysis in astrocytes promotes the production of glutamate, which can be converted to -ketoglutarate by aminotransferation, followed by reductive carboxylation to complement the tricarboxylic acid cycle intermediates, which serve as fuel for neuronal mitochondria**. Upregulating glycolysis and glutamine breakdown in this way leads to a state of increased metabolic and excitatory activity in the brain, which researchers believe is the basis for the subjective experience of mania. Under normal conditions, this mechanism has adaptive functions that transiently upregulate brain metabolism in response to acute energy demands. However, when this mechanism is used for a long time to counteract impaired oxidative metabolism, it can become a pathological process.
Testimonials
This study elaborates on the metabolic overspeed hypothesis of mania and supports it through relevant experimental results, which can provide a new way to understand the biological basis of mania.
Title: Human microbiota from drug-**patients with obsessive-compulsive disorder drives beh**ioral symptoms and neuroinflammation via succinic acid in mice
Human microbiota from patients with obsessive-compulsive disorder drives behavioral symptoms and neuroinflammation in mice via succinic acid.
Authors: Ying-Dan Zhang, et al.
Time: 2024-01-25
Journal: Molecular Psychiatry
Impact factor: 11
doi：10.1038/s41380-024-02424-9
Summary:
New evidence suggests that the gut microbiota is strongly associated with psychiatric disorders. However, little is known about the role of the gut microbiota in the development of obsessive-compulsive disorder (OCD). To investigate the contribution of the gut microbiota to the pathogenesis of OCD, the study transplanted fecal microbiota from first-episode, drug-naïve OCD patients or demographically matched healthy individuals into antibiotic-treated non-specific pathogen (SPF) mice, and the results showed that colonization of the OCD microbiota was sufficient to induce core behavioral deficits, including abnormal anxiety-like and obsessive-compulsive behaviors. The researchers used 16S RNA full-length sequencing to analyze the fecal microbiota of mice, and the results showed that the fecal microbiota of OCD-colonized mice was significantly different from that of the control group. Notably, colonization of the microbiota in OCD mice resulted in impaired neuronal morphology and function of MPFCs and inflammation in the MPFCs and colon**. Non-targeted metabolome analysis of serum and MPFC regions showed that succinic acid (SA) accumulated in OCD-colonized mice. SA hinders neuronal activity and induces inflammatory responses in the colon and MPFC, affecting intestinal permeability and brain function, while succinic acid is an important signaling mediator in the gut microbiota-brain-immune tandem process. Dimethyl malonate (DM) has been reported to inhibit the accumulation of succinate oxidation, reduce downstream inflammatory responses and neuronal damage, thereby exerting neuroprotective effects, and helping to partially improve abnormal behavior in obsessive-compulsive mice, attenuating neuroinflammation and intestinal inflammation.
Testimonials
The findings suggest that the gut microbiota may regulate brain function and behavior in mice through succinic acid signaling, promote the pathophysiology of OCD through gut-brain crosstalk, and may provide new insights into this disease.
Title: Life-history stage determines the diet of ectoparasitic mites on their honey bee hosts
Translation: Life history stages determine the diet of ectoparasitic mites in honey bee hosts.
Author: Bin Han et al.
Time: 2024-01-25
Journal: Nature Communications
Index factor: 166
doi：10.1038/s41467-024-44915-x
Summary:
The ectoparasitic mites of the genera Varroa and tropilaelaps have used bees exclusively for food during the evolutionary life history phases alternating between dispersal and reproduction**. The study found that the main food** utilized by the vandal varroa depends on the life history stage of the host. As mentioned earlier, when feeding on adult bees, dispersed vThe destructor feeds on the peritoneum to obtain fat bodies. However, this was confirmed by wound analysis, preferential transfer of biomarkers, and proteomic comparison between parasite and host tissuesWhen destructors feed on bee pupae during the bee breeding stage, they mainly consume hemolymph. The results of biological staining and proteomics are consistent with the corresponding findings of tropilaelaps mercedesae, a mite that feeds only on bee pupae and whose transmission phase is greatly shortened. v.Metabolomic analysis of the destructor confirmed dietary differences between dispersed adult and breeding female mites. The differences in proteome and metabolome between breeding and dispersed adults indicated that the blood lymphatic food of breeding adults was consistent with amino acid metabolism and protein synthesis, while the metabolism of non-breeding adults was compatible with lipid metabolism.
Testimonials
The results of this study reveal the dietary specialization of ectoparasitic mites within the host, which coincides with the life history of the host and the parasite.
Title: Engineered probiotic overcomes pathogen defences using signal interference and antibiotic production to treat infection in mice
Engineered probiotics use signal interference and antibiotic production to overcome pathogen defenses to ** mouse infection.
Author: hackwon do et al.
Date: 2024-01-16
Journal: Nature Microbiology
Impact factor: 283
doi：10.1038/s41564-023-01583-9
Summary:
Probiotic supplements are thought to promote the maintenance of health in the body by preventing colonization by pathogens. However, the mechanistic basis for their efficacy in the body has not yet been fully understood. Using metabolomics and bacterial genetics, the results showed that the human oral probiotic Streptococcus salivarius K12 (SAL) produces sialolactone, an antibiotic that effectively inhibits pathogenic Streptococcus pyogenes (GAS) in vitro and in mice. However, prophylactic administration of SAL enhances the colonization of GAS in mice and in human saliva. Studies have shown that GAS responds to SAL intercellular peptide signaling upon co-colonization, thereby controlling the production of SAL salivary galactoprotein. GAS produces a secreted protease SPEB that targets SALs-derived sialin and improves the survival of GAS. Using this knowledge, the researchers redesigned the probiotic SAL to prevent GAS from gaining signals while enhancing the action of SAL antimicrobials. This engineered probiotic has shown superior efficacy in preventing GAS colonization in the body.
Testimonials
The results of this study suggest that knowledge of interspecies interactions can determine anti-infective strategies based on antibiotics and probiotics.
Title: muscle abnormalities worsen after post-exertional malaise in long covid
Translation: Exercise discomfort in patients with long COVID can exacerbate muscle abnormalities.
Authors: Brent Appelman et al.
Time: 2024-01-04
Journal: Nature Communications
Index factor: 166
doi：10.1038/s41467-023-44432-3
Summary:
A prominent symptom in patients with long COVID is post-exercise fatigue, which is associated with worsening of fatigue and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. Through this longitudinal case-control study (NCT05225688), researchers have gained a new understanding of the pathophysiology of post-exercise fatigue in patients with long COVID. Studies have found that skeletal muscle structure is associated with reduced exercise capacity, and after inducing post-exercise discomfort, local and systemic metabolic disorders, severe exercise-induced myopathy, and tissue infiltration of amyloid deposits in skeletal muscle will worsen in patients with long-term COVID-19.
Testimonials
This study provides new ideas and ways to understand the pathophysiology of post-exertion malaise in patients with long COVID and other post-infectious diseases.