Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP

Abstract

The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut–brain axis, reflecting a bidirectional interaction between the central nervous system and the intestine. A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically, the archetypal model of plasticity, long-term potentiation (LTP), is reduced in hippocampus of middle-aged and aged rats. Because the intestinal microbiota might change with age, we have investigated whether the age-related deficit in LTP might be attenuated by changing the composition of intestinal microbiota with VSL#3, a probiotic mixture comprising 8 Gram-positive bacterial strains. Here, we report that treatment of aged rats with VSL#3 induced a robust change in the composition of intestinal microbiota with an increase in the abundance of Actinobacteria and Bacterioidetes, which was reduced in control-treated aged rats. VSL#3 administration modulated the expression of a large group of genes in brain tissue as assessed by whole gene expression, with evidence of a change in genes that impact on inflammatory and neuronal plasticity processes. The age-related deficit in LTP was attenuated in VSL#3-treated aged rats and this was accompanied by a modest decrease in markers of microglial activation and an increase in expression of BDNF and synapsin. The data support the notion that intestinal microbiota can be manipulated to positively impact on neuronal function.

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

“…These findings suggest that probiotics can fortify the intestinal barrier to mitigate neurotrauma induced endotoxemia and inhibit systemic dysregulation of the immune system that may otherwise peripherally hyper-activate the brain's microglia [187][188][189] . This is supported by emerging evidence from multiple experimental models further suggests that probiotic supplementation may have protective role against LPS induced neurodegeneration 178,179 . Even in the absence of TBI or endotoxemia, the host microbiota inhabiting the gut play a critical role in the maturation and function of the microglia in the brain 89 .…”

Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study

“…The brain is an important reservoir of HIV-1, but it remains unclear if the virus causes of persistent low-grade inflammation during cART, or if the virus—after evolution and adaptation to the environment—drives an inflammatory response in the brain [40,41]. The pivotal role of inducing a status of activation in the CNS is attributed to monocyte-derived macrophages; monocytes entering the CNS differentiate into macrophages, and during activation can produce several substances important in the pathogenesis of neurocognitive disorders [42,43]. The opportunity to reduce the activation of the IDO pathway through this probiotic product could break the vicious gut–brain circle and in this manner prevent the neurocognitive impairment observed in HIV-1-positive patients.…”

Recent developments in understanding the role of the gut microbiota in brain health and disease

“…For instance, grape seed polyphenol extracts 3‐hydroxybenzoic acid and 3‐(3‐hydroxyphenyl)propionic acid were shown to prevent the assembly of Aβ 1–42 into toxic fibrils in vitro , suggesting that a polyphenol‐rich diet may attenuate amyloid accumulation in the brain . The probiotic mixture VSL#3 (combination of Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei , and L. delbrueckii subspecies Bulgaricus) attenuated age‐related deficits in long‐term potentiation, suggesting an improvement in memory, in rats while also ameliorating age‐related microglial activation . Despite these interesting preliminary preclinical studies, more studies are required with both aged and transgenic animals to determine whether diet or probiotics may be employed into the clinical setting as a preventative measure for the onset of Alzheimer's disease.…”