The aim of the present study was to determine whether there is the mechanistic connection between antibacterial-dependent gut microbiota disturbance and anxiety. First, exposure of mice to ampicillin caused anxiety and colitis and increased the population of Proteobacteria, particularly Klebsiella oxytoca, in gut microbiota and fecal and blood lipopolysaccharide levels, while decreasing lactobacilli population including Lactobacillus reuteri. Next, treatments with fecal microbiota of ampicillin-treated mouse (FAP), K. oxytoca, or lipopolysaccharide isolated from K. oxytoca (KL) induced anxiety and colitis in mice and increased blood corticosterone, IL-6, and lipopolysaccharide levels. Moreover, these treatments also increased the recruitment of microglia (Iba1⁺), monocytes (CD11b⁺/CD45⁺), and dendritic cells (CD11b⁺/CD11c⁺) to the hippocampus, as well as the population of apoptotic neuron cells (caspase-3⁺/NeuN⁺) in the brain. Furthermore, ampicillin, K. oxytoca, and KL induced NF-κB activation and IL-1β and TNF-α expression in the colon and brain as well as increased gut membrane permeability. Finally, oral administration of L. reuteri alleviated ampicillin-induced anxiety and colitis. These results suggest that ampicillin exposure can cause anxiety through neuro-inflammation which can be induced by monocyte/macrophage-activated gastrointestinal inflammation and elevated Proteobacteria population including K. oxytoca, while treatment with lactobacilli suppresses it.

Recently, studies on the relationship between gut dysbiosis and Parkinson’s disease (PD) have increased, but whether a specific gut bacterium may cause PD remains unexplored. Here, we report, for the first time, that a specific gut bacterium directly induces PD symptoms and dopaminergic neuronal damage in the mouse brain. We found that the number of Enterobacteriaceae, particularly Proteus mirabilis, markedly and commonly increased in PD mouse models. Administration of P. mirabilis isolated from PD mice significantly induced motor deficits, selectively caused dopaminergic neuronal damage and inflammation in substantia nigra and striatum, and stimulated α-synuclein aggregation in the brain as well as in the colon. We found that lipopolysaccharides, a virulence factor of P. mirabilis, may be associated in these pathological changes via gut leakage and inflammatory actions. Our results suggest a role of P. mirabilis on PD pathogenesis in the brain.

Aim We isolated Lactobacillus brevis G‐101 from kimchi lactic acid bacteria (LAB) strains, which induced IL‐10 expression in lipopolysaccharide (LPS)‐stimulated peritoneal macrophages. To evaluate the inflammatory effect of G‐101, we examined its inhibitory effect in 2,4,6‐trinitrobenzene sulfonic acid (TNBS)‐induced colitic mice. Materials and Results The colitic mice were prepared by intrarectal injection of TNBS. We measured intestinal mucosal cytokines by enzyme‐linked immunosorbent assay; activation of transcription factors, by immunoblotting; and macrophage polarization markers, by real‐time polymerase chain reaction. Of 200 LAB strains tested, Lact. brevis G‐101 showed most potent activity for induction of IL‐10 expression in LPS‐stimulated peritoneal macrophages. However, it significantly inhibited the expression of TNF‐α, IL‐1β and IL‐6 and the phosphorylation of IRAK1 and AKT, and activated NF‐κB and MAPKs. Treatment with TNBS caused colon shortening; increased myeloperoxidase activity; and increased IL‐1β, IL‐6 and TNF‐α expression in mice. Oral administration of Lact. brevis G‐101 significantly inhibited these activities. Lactobacillus brevis G‐101 inhibited TNBS‐induced IRAK‐1 phosphorylation and NF‐κB activation, as well as the expression of COX‐2 and iNOS. Lactobacillus brevis G‐101 inhibited the expression of M1 macrophage markers, but increased the expression of M2 macrophages in the colons of TNBS‐treated mice. Conclusions Lactobacillus brevis G‐101 may improve colitis by inhibiting the IRAK1/NF‐κB, MAPK and AKT pathways and by polarizing M1 macrophages to M2‐like macrophages. Significance and Impact of the Study These results suggest that IL‐10 expression‐inducing LAB can ameliorate colitis by inhibiting NF‐κB activation and macrophage polarization.