Gastroenterology and Effects on Health & Behavior

Endotoxemia occurs when endotoxin or lipopolysaccharide from the cell wall of gram-negative bacteria are absorbed into circulation, activating the release of host-derived inflammatory mediators. Chronic endotoxemia occurs with human obesity and induces systemic inflammation, which can lead to metabolic syndrome. Eight healthy human volunteers in this study were fed a prudent-style or a Western-style diet for 1 month, with a 1-month washout period between diets. Both diets had slightly over 2200 calories, but the prudent-style diet contained less fat, more carbohydrates, and more calcium and fiber. Protein levels were the same and physical activity (measured with a pedometer) was nearly the same with either diet. There was a significant increase in plasma endotoxin activity levels after participants ate the Western-style diet and a decrease after the prudent-style diet. Feeding the prudent-style diet resulted in a significant decrease in serum TNF-α. There was also a trend for reduced monocyte chemotactic protein 1 and interleukin-8 levels, none of which changed with the Western-style diet. Based on this study, therapy to reduce endotoxemia might reduce systemic inflammation in patients with GI disease or metabolic syndrome.

Source
A high-fat diet is associated with endotoxemia that originates from the gut. Pendyala S, Walker JM, Holt PR. GASTROENTEROL 142:1100-1101, 2012.

Changes in the microbial composition of the GI tract are thought to contribute to inflammatory and functional bowel disorders and psychiatric comorbidities. This study was designed to evaluate whether changing the intestinal microbiota of mice affects their behavior and brain biochemistry. The mice were either specific pathogen-free (SPF) BALB/c (with/without subdiaphragmatic vagotomy or chemical sympathectomy), germ-free BALB/c, or NIH Swiss. Except the NIH Swiss mice, all received a mixture of nonabsorbable antimicrobials in their drinking water for 7 days. The germ-free BALB/c and NIH Swiss mice were colonized with microbiota from SPF NIH Swiss or BALB/c mice. Behavior was evaluated using step-down and light preference tests. Histologic, myeloperoxidase, and cytokine analyses were run on gut samples. Enzyme-linked immunoassay was used to assess for brain-derived neurotrophic factor (BDNF), serotonin, noradrenaline, and dopamine. The study found that oral antimicrobials can cause changes in the intestinal microbiota, resulting in increased BDNF and exploratory behavior; these normalized once the antibiotic was withdrawn. Results of this study provided strong evidence for a microbiota–gut–brain axis that can influence brain biochemistry and modulate adult mice behavior.

Source
The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Bercik P, Denou E, Collins J, et al. GASTROENTEROL 141:599-609, 2011.

Commentary
I have had a long-time interest in gastroenterology; each month I try to catch up on new developments when the gastroenterology journals arrive. There is so much going on and so many advances in this field: it is almost unreal. Readers will remember learning about intestinal flora and bacterial overgrowth. New terms found in literature for these familiar names include intestinal microbiota/microbiome and dysbiosis. Our intestinal tracts contain approximately 10 times more cells than in the body, and we continue to learn about the complex relationships we have with this vast and still poorly understood ecosystem. The microbiome performs a multitude of diverse functions, including a possible role in the genesis of obesity. Enteric bacteria have been implicated as a risk factor for inflammatory bowel disease and dysbiosis has been associated with irritable bowel syndrome (IBS) in humans. Now, pet foods come with prebiotics and we treat our patients with probiotics in an effort to modify the microbiome; more developments are doubtless coming.

These articles are examples of the emerging knowledge in this field. The fact that the microbiome can affect behavioral patterns is fascinating and may be relevant to such conditions as IBS, raising the possibility that intestinal dysbiosis may contribute to behavioral changes in these patients. In the other article, a high-fat Western diet was reportedly associated with increased circulating endotoxin levels. Our diets might well contribute to endotoxemia by causing changes in GI-barrier function or the composition of the microbiota. This will perhaps give us cause to pause next time we order that prime rib.—Colin F. Burrows, BVetMed, PhD, HonFRCVS, DACVIM

This capsule is apart of the One Health Initiative.