Reducing the excessive inflammation after burn injury in aged mice by maintaining a healthier intestinal microbiome.

One in six people are projected to be 65 years or older by 2050. As the population ages, better treatments for injuries that disproportionately impact the aged population will be needed. Clinical studies show that people aged 65 and older experience higher rates of morbidity and mortality after burn injury, including a greater incidence of pulmonary complications when compared to younger burn injured adults, which we and others believe is mediated, in part, by inflammation originating in the intestines.

Advanced Age Worsens Respiratory Function and Pulmonary Inflammation After Burn Injury and This Correlates With Changes in the Fecal Microbiome in Mice.

Cutaneous burn injury in the elderly is associated with poor clinical outcomes and increased pulmonary-related complications. We and others have shown that burn injury triggers a cascade of inflammatory mediators which increase gut permeability and dysbiosis of the fecal microbiota and this is more dramatic in the aged. Since crosstalk between intestinal microbes and the lung, termed the "gut-lung axis," impacts immunity and homeostasis in the airway, we hypothesized that the increased intestinal dysbiosis in age and burn injury may contribute to excessive pulmonary inflammation and poor prognosis after injury.

Ethanol exacerbates pulmonary complications after burn injury in mice, regardless of frequency of ethanol exposures.

Burn injuries are associated with significant morbidity and mortality, and lungs are the most common organ to fail. Interestingly, patients with alcohol intoxication at the time of burn have worse clinical outcomes, including pulmonary complications. Using a clinically relevant murine model, we have previously reported that episodic ethanol exposure before burn exacerbated lung inflammation.

REMOTE BURN INJURY IN AGED MICE INDUCES COLONIC LYMPHOID AGGREGATE EXPANSION AND DYSBIOSIS OF THE FECAL MICROBIOME WHICH CORRELATES WITH NEUROINFLAMMATION.

The Earth's population is aging, and by 2050, one of six people will be 65 years or older. Therefore, proper treatment of injuries that disproportionately impact people of advanced age will be more important. Clinical studies reveal people 65 years or older account for 16.

Cutaneous burn injury induces neuroinflammation and reactive astrocyte activation in the hippocampus of aged mice.

Background: By 2050, one in six people globally will be 65 or older. Confusion and delirium are significant complications after burn injury, especially in the elderly population. The etiology is still unknown, however complications may be driven by pro-inflammatory activation of astrocytes within the hippocampus (HPC) after burn injury.

Aging, Cutaneous Burn Injury and Multi-Organ Complications: The Role of the Gut.

Advanced age escalates post-burn complications and older burn patients, and even those with relatively minor burns, have worse clinical outcomes after injury. While the mechanism(s) responsible for the compounding effects of age and burn injury have not been defined, in this viewpoint, we highlight the emerging data suggesting that age-mediated impairment of gut barrier integrity and dysbiosis of the fecal microbiome in older subjects may play a role in the heightened multi-organ responses seen in older patients. Studies aimed at exploring the contribution of intestinal dysfunction in age-related exacerbations of post-burn inflammatory responses could highlight novel therapeutic interventions that can be used to treat victims of burns and other traumatic injuries.

Advanced age exacerbates intestinal epithelial permeability after burn injury in mice.

Background: Advanced age is an independent risk factor for morbidity and mortality after burn injury. Following burn, the intestines can become permeable leading to the leakage of bacteria and their products from the lumen of the ileum to the portal and systemic circulation. Here, we sought to determine the effects of advanced age on intestinal permeability post burn injury and assess intestinal inflammatory biomarkers.

Advanced age heightens hepatic damage in a murine model of scald burn injury.

Background: Elderly burn patients exhibit a lower survival rate compared with younger counterparts. The liver is susceptible to damage after burn injury, which predisposes to poor outcomes. Lipid homeostasis and the antioxidant glutathione system play fundamental roles in preserving liver integrity.

Age-related changes in intestinal immunity and the microbiome.

The gastrointestinal (GI) tract is a vitally important site for the adsorption of nutrients as well as the education of immune cells. Homeostasis of the gut is maintained by the interplay of the intestinal epithelium, immune cells, luminal Ags, and the intestinal microbiota. The well-being of the gut is intrinsically linked to the overall health of the host, and perturbations to this homeostasis can have severe impacts on local and systemic health.

IFN-γ and IL-17A regulate intestinal crypt production of CXCL10 in the healthy and inflamed colon.

During intestinal inflammation, immature cells within the intestinal crypt are called upon to replenish lost epithelial cell populations, promote tissue regeneration, and restore barrier integrity. Inflammatory mediators including T1/T17-associated cytokines influence tissue health and regenerative processes, yet how these cytokines directly influence the colon crypt epithelium and whether the crypt remains responsive to these cytokines during active damage and repair, remain unclear. Here, using laser-capture microdissection and primary colon organoid culture, we show that the cytokine milieu regulates the ability of the colonic crypt epithelium to participate in proinflammatory signaling.

DNA damage response genes mark the early transition from colitis to neoplasia in colitis-associated colon cancer.

Chronic intestinal inflammation predisposes patients with Inflammatory Bowel Disease (IBD) to Colitis-Associated Cancer (CAC). In the setting of chronic inflammation, microsatellite instability (MSI) results from early loss of DNA damage response (DDR) genes, ultimately leading to tumor formation. Despite continued efforts to improve early detection of high risk, pre-dysplastic regions in IBD patients, current macroscopic and genetic surveillance modalities remain limited.

Cytokine crowdsourcing: multicellular production of TH17-associated cytokines.

In the 2 decades since its discovery, IL-17A has become appreciated for mounting robust, protective responses against bacterial and fungal pathogens. When improperly regulated, however, IL-17A can play a profoundly pathogenic role in perpetuating inflammation and has been linked to a wide variety of debilitating diseases. IL-17A is often present in a composite milieu that includes cytokines produced by TH17 cells (i.