Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is characterized by its clinical and biological heterogeneity. The clinical prognostic implications of tumor-associated macrophages (TAMs) in DLBCL remain controversial and the correlation between TAMs and peripheral absolute monocyte count (AMC) has not yet been elucidated.MethodsIn 221 untreated, newly diagnosed patients with DLBCL, we evaluated the prognostic value of TAMs using immunohistochemical analysis, as well as the association of TAMs and AMC.ResultsWe found that high CD68 or high CD163 expression was correlated with clinicopathological characteristics, high CD163 expression was an adverse predictor for both overall survival (OS) [hazard ratio (HR) = 2.265, P = 0.005] and progression- free survival (PFS) (HR = 1.925, P = 0.017) in patients with DLBCL. Patients with high CD68 or high CD163 expression had significantly poorer OS and PFS than those with low CD68 or low CD163 expression, respectively (CD68: OS: P<0.001, PFS: P<0.001; CD163: OS: P<0.001, PFS: P<0.001), even in the rituximab era. Moreover, high-risk patients could be further identified by the expression of CD68 or CD163, especially in those classified as low/intermediate risk by International Prognostic Index (IPI). Furthermore, the significant positive correlation was also detected between CD68 expression or CD163 expression and AMC (r = 0.256, P<0.001; r = 0.303, P<0.001).ConclusionsPatients with high expression of TAMs tend to have poorer OS and PFS, even in the rituximab era, and have positive correlation with AMC. Therefore, the peripheral AMC is a useful prognostic marker reflecting the status of the tumor microenvironment (TME) in DLBCL.

Asthma is an epithelial disorder in which T helper 2 (Th2)-type inflammation has a prominent role. Recent studies indicated that a cytokine, thymic stromal lymphopoietin (TSLP), is essential for the development of antigen-induced asthma. The authors used ovalbumin (OVA) sensitization and challenge to induce a murine asthmatic model. The model was confirmed by airway hyperresponsiveness, serum levels of total and OVA-specific immunoglobulin (IgE), histological analysis of lung tissues. The authors found that expression of TSLP was significantly increased in both mRNA and protein levels in mice lungs treated with OVA. The expression of CD40, CD80, and CD86 in bronchoalveolar lavage fluid (BALF) was increased in mice with OVA. Tight correlation between TSLP mRNA and interleukin (IL)-4, IL-5, and IL-13 in BALF was identified. Furthermore, treating mice with TSLP-neutralizing antibody reduced the expression of TSLP mRNA of lungs, CD40, CD80, and CD86 on dendritic cells, and IL-4, IL-5, and IL-13 in the OVA group. This study indicates that TSLP is increased in the airway epithelium in mice treated with OVA. In the lung inflammation model, TSLP activates dendritic cells (DCs) via up-regulation of CD40, CD80, and CD86, then induces the differentiation of prime naive CD4(+) T cells to become proinflammatory Th2 cells. Blocking TSLP is capable of inhibiting the production of Th2 cytokines, thus presents a promising strategy for the treatment of asthma.

Aberrant innate and adaptive immune responsed to allergens and environmental pollutants lead to respiratory allergic disease such as asthma. In this study, we focused on toll-like receptor-4 (TLR4) expressed on airway epithelium to identify house dust mite (HDM)-regulated allergic inflammation via TLR4 signaling pathway and the triggering to alveolar macrophages (AM)-driven adaptive immune response. The authors found that mouse exposed to HDM showed more eosinophils, neutrophils, monocytes, lymphocytes as well as total cells in bronchoalveolar lavage fluid (BALF) confirmed by flow cytometry. Besides, the expression of TLR4 in airway epithelial cells was significantly increased in both mRNA and protein levels in mice treated with HDM and the expression of CD40 and CD86 in AM was also increased in mice exposed to HDM. Tight correlation between TLR4 protein and CD40, CD86 in AM was identified. This study demonstrates that TLR4 expression on airway epithelium played an essential role in HDM-induced activation of AM in immune responses and allergic inflammation. The airway epithelial TLR4 signaling pathway revealed tight connection between endotoxin exposure and asthma prevalence in the clinic.

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