Abstract
Microbiota dysbiosis has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological changes affecting the gut-brain neural axis, mental health, and general well-being. However, current animal studies using oral gavage and gnotobiotic animals do not allow for non-invasive long-term access to gut microbiome. The purpose of the present study was to evaluate the feasibility of 3D-printed fistula implants through the body wall and into the cecum of rats to obtain long-term access to gut microbiome. Cecal fistulas were designed and 3D-printed using a high temperature resin (Formlabs; acrylic and methacrylic mixture). Nine male Sprague-Dawley rats underwent the fistula implantation. Food intake, body weight, and body fat were measured to determine the impact of fistula manipulation. Gut microbiome, vagal afferents in the hindbrain, and microglia activation were analyzed to determine if fistula implantation disrupted the gut-brain neural axis. We found that the procedure induced a transient decrease in microbial diversity in the gut that resolved within a few weeks. Fistula implantation had no impact on food intake, body weight, fat mass, or microglia activation. Our study shows that 3D-printed cecal fistula implantation is an effective procedure that allows long-term and minimally invasive access to gut microbiome.
Highlights
The gut microbiome has become an area of intense study for contemporary researchers
There was no difference in food intake between the groups, except for a spike when the high-fat diet was first introduced to the HFD/F group (Figure 4A)
Cecal fistula manipulation did not impact food intake, body weight, or fat mass. These results indicate the implantation of a cecal fistula is an effective procedure that allows long-term and minimally invasive access to the gut microbiome to better facilitate future studies on microbiome transplants by minimizing the limitations of currently used methods in the field of microbiome research
Summary
The gut microbiome has become an area of intense study for contemporary researchers. Studies have shown that the gut microbiome plays a crucial role in early physiological development in humans, influencing everything from bone growth to the outcome of diseases such as asthma and certain neurodevelopmental disorders [1]. Germ-free animals (GF), which lack all microorganisms including the gut microbiome, exhibit altered expression of motor control and anxiety-like behavior [2], decreased microglia development in the brain, inhibited responses to spatial and temporal stimuli, and increased blood-brain barrier permeability [3]. They have been shown to have arrested the growth of capillary networks [4]. Consumption of a high-fat/high sugar diet rapidly, within a few weeks, increased ratio of Firmicutes/Bacteroidetes species and decreased in overall microbiota diversity [5,6,7].
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