The intestinal barrier encompasses structural, permeability and immune aspects of the gut mucosa that, when disrupted, may contribute to chronic inflammation. Although gnotobiotic studies have demonstrated the effects of microbiota on mucosal and systemic immunity, as well as intestinal barrier architecture and innate immune characteristics, its impact on barrier function remains unclear. We compared germ-free and conventional mice, as well as mice colonized with human fecal microbiota that were followed for 21 days post-colonization. Colonic barrier structure was investigated by immunohistochemistry, molecular and electron microscopy techniques. Permeability was assessed in colon tissue by Ussing chambers, and by serum LPS and MDP detection using TLR4- and NOD2-NFκB reporter assays. Microbiota profile was determined by Illumina 16S rRNA gene sequencing. Low dose dextran sodium sulfate was administered to assess microbiota-induced barrier changes on resistance to colonic injury. Permeability to paracellular probes and mucus layer structure resembled that of conventional mice by day 7 post-colonization, coinciding with reduced claudin-1 expression and transient IL-18 production by intestinal epithelial cells. These post-colonization adaptations were associated with decreased systemic bacterial antigen exposure and reduced susceptibility to intestinal injury. In conclusion, commensal colonization promotes physiological barrier structural and functional adaptations that contribute to intestinal homeostasis.
BACKGROUND: Traumatic brain injury has multiple impacts on gait including decreased speed and increased gait variability. Rhythmic auditory stimulation (RAS) gait training uses the rhythm and timing structure of music to train and ultimately improve slow and variable walking patterns. OBJECTIVE: To describe the feasibility of RAS gait training in community-dwelling adults with traumatic brain injury (TBI). A secondary objective is to report changes in spatiotemporal gait parameters and clinical measures of balance and walking endurance. METHODS: Two individuals with a TBI participated in nine sessions of gait training with RAS over a 3-week period. At baseline, post-training and 3-week follow-up, spatiotemporal parameters of walking were analyzed at preferred pace, maximum pace and dual-task walking conditions. Secondary outcomes included the Community Balance and Mobility Scale and the 6-Minute Walk Test. Feasibility was assessed using reports of physical fatigue, adverse event reporting, and perceived satisfaction. RESULTS: Both participants completed all 9 planned intervention sessions. The sessions were well tolerated with no adverse events. Participant 1 and 2 exhibited different responses to the intervention in line with the therapeutic goals set with the therapist. Participant 1 exhibited improved speed and decreased gait variability. Participant 2 exhibited reduced gait speed but less fatigue during the 6MWT. CONCLUSIONS: RAS was found to be a safe and feasible gait intervention with the potential to improve some aspects of gait impairments related to gait speed, gait variability, dynamic balance and walking endurance. Further investigation including a pilot randomized controlled trial is warranted.
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