The gut microbiota is made up of trillions of microbial cells including bacteria, viruses, fungi, and other microbial bodies and is greatly involved in the maintenance of proper health of the host body. In particular, the gut microbiota has been shown to not only be involved in brain development but also in the modulation of behavior, neuropsychiatric disorders, and neurodegenerative diseases including Alzheimer’s disease. The precise mechanism by which the gut microbiota can affect the development of Alzheimer’s disease is unknown, but the gut microbiota is thought to communicate with the brain directly via the vagus nerve or indirectly through signaling molecules such as cytokines, neuroendocrine hormones, bacterial components, neuroactive molecules, or microbial metabolites such as short-chain fatty acids. In particular, interventions such as probiotic supplementation, fecal microbiota transfer, and supplementation with microbial metabolites have been used not only to study the effects that the gut microbiota has on behavior and cognitive function, but also as potential therapeutics for Alzheimer’s disease. A few of these interventions, such as probiotics, are promising candidates for the improvement of cognition in Alzheimer ’s disease and are the focus of this review.

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The right ventricle (RV) of the heart normally encounters low pressure and high volume, but under increased afterload from elevated vascular resistance or outflow tract obstruction, undergoes adaptive hypertrophy followed by maladaptive remodeling. This is similar to what is found in left ventricle pathology (LV) except that RV dysfunction features exaggerated cardiac fibrosis compared to that found in the LV, which greatly worsens clinical outcomes. We sought to investigate the cellular environment of the rat RV in an effort to discover novel treatment strategies for RV dysfunction in failure found in patients with cor pulmonale. Sprague‐Dawley rats treated in hypoxia (10% O2) developed RV dysfunction as noted via echocardiography (decreased tricuspid annular plane systolic excursion, P<0.05 via t‐test) and increased RV weight relative to the LV and septum (P<0.05 via t‐test) compared to control rats (room air). Trichrome staining revealed that hypoxia‐treated rats had perfuse interstitial fibrosis in the RV, but not the LV. Expression of fibrotic mediators was increased in the RV of both control and hypoxia‐treated rats, including fibronectin‐1, periostin, and connective tissue growth factor (CTGF), but not collagen 1, as revealed by qPCR. These differences in gene expression indicate not only does hypoxia cause increased fibrosis in the RV, but also that the RV has innately increased fibrotic factors even under control conditions compared to the LV. This was supported by immunofluorescent imaging of vimentin, an intermediate filament expressed in fibroblasts, which displayed higher expression in the RV of control rats compared to the LV, with strongest expression in the RV of hypoxia‐treated rats. To investigate the role of fibroblasts in RV hypertrophy, we performed enzymatic tissue digests to obtain cultured fibroblasts. Fibroblasts isolated from the RV of both hypoxia‐ and normoxia‐treated rats proliferated at a faster rate and treatment with TGF‐β caused a greater response in the fibroblasts from the RV compared to the LV as measured by expression of periostin and CTGF. Thus, our results demonstrate that the RV, as compared to the LV, is primed for a fibrotic response. This may explain the exaggerated fibrotic phenotype found in both human RV disease and animal models of RV hypertrophy.

Alzheimer disease (AD) which is a progressive, neurodegenerative disease characterized by neuroinflammation and accumulation of amyloid‐β (Aβ) fibers leading to neuronal death. It is theorized that a combination of host genetics and environmental factors contribute to AD development and progression, however the trigger for neuroinflammation and Aβ development has remained elusive. One such environmental exposure linked to AD development and progression is air pollution. Thus, we designed a study to test our hypothesis that air particulate matter exposure accelerates AD development and progression. Male, wild type (WT) C57Bl/6 and AD transgenic mice, APPswe/PSEN1dE9 (APP/PS1), were exposed to either filtered air (FA) or air particulate matter sized under 2.5 μm (PM2.5) for 6 hrs/day, 5 days/week for 3 months. Brain tissue was collected at the end of the 3 month exposure and was either flash frozen or formalin‐fixed. Results demonstrated a significant increase in hippocampal Aβ accumulation in PM2.5‐exposed APP/PS1 mice over that of FA‐exposed APP/PS1 animals. PM2.5‐exposed WT mice did not develop Aβ plaques. Immune markers CD68 (tissue macrophage) and IBA1 (activated microglia) and the glial marker GFAP (activated astrocytes), as assessed by immunohistochemistry, were also significantly increased in PM2.5‐exposed APP/PS1 mice over their FA‐exposed counterparts. PM2.5‐exposure did not lead to enhanced levels of CD68, IBA1, or GFAP in WT mice. Taken together, these data suggest that airborne particulate matter has the propensity to alter the brain environment in mice genetically predisposed to develop Aβ in a way that mimics early AD‐like pathology. Support or Funding Information Funding support from AG057046 to LEW and CKC.