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Man and the Microbiome: A New Theory of Everything?
Butler, MI, Cryan, JF, Dinan, TG
Annual review of clinical psychology. 2019;:371-398
Abstract
The gut microbiome is implicated in the pathophysiology of a wide range of psychological disorders. Preclinical studies have provided us with key insights into the mechanisms by which the microbiome influences bidirectional gut-brain communication. There are many signaling pathways involved, including the hypothalamic-pituitary-adrenal axis, immune modulation, tryptophan and serotonin metabolism, bile acid transformation, microbial production of neuroactive compounds, and regulation of the endocannabinoid system. The complex and widespread influence of the microbiome on many physiological and psychological processes has generated a keen interest in its therapeutic potential for depression, anxiety, autism, and other psychiatric disorders. It has been shown that the microbiome composition of people suffering with such conditions differs significantly from that of healthy controls, and although the area is in its infancy, interventional studies that alter a person's microbiome through the use of probiotics, prebiotics, or dietary change can alleviate psychopathological symptoms.
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Gut microbiota, obesity and diabetes.
Patterson, E, Ryan, PM, Cryan, JF, Dinan, TG, Ross, RP, Fitzgerald, GF, Stanton, C
Postgraduate medical journal. 2016;(1087):286-300
Abstract
The central role of the intestinal microbiota in the progression and, equally, prevention of metabolic dysfunction is becoming abundantly apparent. The symbiotic relationship between intestinal microbiota and host ensures appropriate development of the metabolic system in humans. However, disturbances in composition and, in turn, functionality of the intestinal microbiota can disrupt gut barrier function, a trip switch for metabolic endotoxemia. This low-grade chronic inflammation, brought about by the influx of inflammatory bacterial fragments into circulation through a malfunctioning gut barrier, has considerable knock-on effects for host adiposity and insulin resistance. Conversely, recent evidence suggests that there are certain bacterial species that may interact with host metabolism through metabolite-mediated stimulation of enteric hormones and other systems outside of the gastrointestinal tract, such as the endocannabinoid system. When the abundance of these keystone species begins to decline, we see a collapse of the symbiosis, reflected in a deterioration of host metabolic health. This review will investigate the intricate axis between the microbiota and host metabolism, while also addressing the promising and novel field of probiotics as metabolic therapies.
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Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut.
Groeger, D, O'Mahony, L, Murphy, EF, Bourke, JF, Dinan, TG, Kiely, B, Shanahan, F, Quigley, EM
Gut microbes. 2013;(4):325-39
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Abstract
Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear. In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding. These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.
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Probiotics in transition.
Shanahan, F, Dinan, TG, Ross, P, Hill, C
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2012;(11):1220-4
Abstract
Despite the hyperbole often linked with a popular research field, the scientific rationale for probiotics is sound. The probiotic concept is not new but is undergoing transition as knowledge of the gut microbiota in health and disease becomes translated to the clinic. Operationally, a probiotic represents a mimic of and/or supplement to the normal gut microbiota. Much confusion has arisen among consumers because of media misportrayals of probiotics as all being the same. However, with clarification of the molecular basis of host-microbe interactions, the selection criteria for probiotics and the delineation of their distinct mechanisms of action are improving. Most probiotics are from the genus Lactobacillus or Bifidobacterium; this is likely to change and diversify. Similarly, the development of new therapeutic strategies, such as the development of phagebiotics, psychobiotics, and genetically modified pharmabiotics, is poised to become a therapeutic reality.