Mycobacterium vaccae alleviates allergic airway inflammation and airway hyper-responsiveness in asthmatic mice by altering intestinal microbiota.

Host immunity can influence the composition of the gut microbiota and consequently affect disease progression. Previously, we reported that a Mycobacterium vaccae vaccine could ameliorate allergic inflammation in asthmatic mice by regulating inflammatory immune processes. Here, we investigated the anti-inflammatory effects of M. vaccae on allergic asthma via gut microbiota modulation. An ovalbumin (OVA)-induced asthmatic murine model was established and treated with M. vaccae. Gut microbiota profiles were determined in 18 BALB/c mice using 16S rDNA gene sequencing and metabolomic profiling was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Mycobacterium vaccae alleviated airway hyper-reactivity and inflammatory infiltration in mice with OVA-induced allergic asthma. The microbiota of asthmatic mice is disrupted and that this can be reversed with M. vaccae. Additionally, a total of 24 differential metabolites were screened, and the abundance of PI(14:1(9Z)/18:0), a glycerophospholipid, was found to be correlated with macrophage numbers (r = 0.52, p = 0.039). These metabolites may affect chemokine (such as macrophage chemoattractant protein-1) concentrations in the serum, and ultimately affect pulmonary macrophage recruitment. Our data demonstrated that M. vaccae might alleviate airway inflammation and hyper-responsiveness in asthmatic mice by reversing imbalances in gut microbiota. These novel mechanistic insights are expected to pave the way for novel asthma therapeutic strategies.

Mycobacterium vaccae attenuates airway inflammation by inhibiting autophagy and activating PI3K/Akt signaling pathway in OVA-induced allergic airway inflammation mouse model.

PURPOSE: The etiology of asthma remains elusive, with no known cure. Based on accumulating evidence, autophagy, a self-degradation process that maintains cellular metabolism and homeostasis, participates in the development of asthma. Mycobacterium vaccae vaccine (M. vaccae), an immunomodulatory agent, has previously been shown to effectively alleviate airway inflammation and airway remodeling. However, its therapeutic effect on asthma via the regulation of autophagy remains unknown. Therefore, this study aimed to investigate the impact of M. vaccae in attenuating asthma airway inflammation via autophagy-mediated pathways. METHODS: Balb/c mice were used to generate an ovalbumin (OVA)-immunized allergic airway model and were subsequently administered either M. vaccae or M. vaccae + rapamycin (an autophagy activator) prior to each challenge. Next, airway inflammation, mucus secretion, and airway remodeling in mouse lung tissue were assessed via histological analyses. Lastly, the expression level of autophagy proteins LC3B, Beclin1, p62, and autolysosome was determined both in vivo and in vitro, along with the expression level of p-PI3K, PI3K, p-Akt, and Akt in mouse lung tissue. RESULTS: The findings indicated that aerosol inhalation of M. vaccae in an asthma mouse model has the potential to decrease eosinophil counts, alleviate airway inflammation, mucus secretion, and airway remodeling through the inhibition of autophagy. Likewise, M. vaccae could reduce the levels of OVA-specific lgE, IL-5, IL-13, and TNF-α in asthma mouse models by inhibiting autophagy. Furthermore, this study revealed that M. vaccae also suppressed autophagy in IL-13-stimulated BEAS-2B cells. Moreover, M. vaccae may activate the PI3K/Akt signaling pathway in the lung tissue of asthmatic mice. CONCLUSION: In summary, the present study suggests that M. vaccae may contribute to alleviating airway inflammation and remodeling in allergic asthma by potentially modulating autophagy and the PI3K/Akt signaling pathway. These discoveries offer a promising avenue for the development of therapeutic interventions targeting allergic airway inflammation.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research.

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.