Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III – convergence toward clinical trials

Abstract

Rapid scientific and technological advances have allowed for a more detailed understanding of the relevance of intestinal microbiota, and the entire body-wide microbiome, to human health and well-being. Rodent studies have provided suggestive evidence that probiotics (e.g. lactobacillus and bifidobacteria) can influence behavior. More importantly, emerging clinical studies indicate that the administration of beneficial microbes, via supplementation and/or fecal microbial transplant (FMT), can influence end-points related to mood state (glycemic control, oxidative status, uremic toxins), brain function (functional magnetic resonance imaging fMRI), and mental outlook (depression, anxiety). However, despite the advances in the area of gastro-biological psychiatry, it becomes clear that there remains an urgent need to explore the value of beneficial microbes in controlled clinical investigations. With the history explored in this series, it is fair to ask if we are now on the cusp of major clinical breakthroughs, or are we merely in the quicksand of Autointoxication II?

Gastrointestinal microbiota in children with autism in Slovakia

“…It is well known and it was already shown not only in animal models, but also in human studies, that probiotics change intestinal microbiota, influence immunity, and stabilize the mucosal barrier [49,50]. In more recent studies it has been also shown that probiotics influence the 'gut-brain' axis modeling the behavior in the way that significantly reduces anxiety, depression, and stress [6,50,51].…”

Obese-type Gut Microbiota Induce Neurobehavioral Changes in the Absence of Obesity

“…Accordingly, the varying combinations of bacteria within individuals has been suggested to underlie variable host susceptibility to illness (13),(14), including neuropsychiatric impairment (15),(16). For example, specific alterations in colon bacteria are associated with cognitive impairment in patients with hepatic encephalopathy (17), and clinical studies show that oral probiotics decrease anxiety and improve mental outlook (18),(19). Furthermore, animal studies have shown that behavior and synaptic plasticity are altered in germ-free mice, and that this phenotype is reversed by microbiome colonization (20).…”

Gastroenvironmental distress: metaphorical antecedents of the gut microbiome

“…Heterogeneous opinions also led to the development of other therapies, including the oral administration of lactic acid-producing bacteria thought to mitigate toxaemia's effects. As Bested et al argue, these interventions represent clear antecedents to contemporary probiotics with a proposed mechanism that retains relative legitimacy in a contemporary light 16. Indeed, while faecal matter was not on its own used as therapy, there was precedent in the early twentieth century for rectally administered preparations of bacterial cultures and vaccines derived from heat-killed faecal bacteria given at sequentially higher doses to induce immunity 15…”