This week Canadian physician Alison C. Bested and her colleagues Alan C. Logan and Eva M. Selhub have published a series of review papers (1, 2, 3) in Gut Pathogens related to the gut microbiota and mental health. Much has been written lately concerning the gut microbiota-brain connection (mediated by CNS, immune, nutrient and other mechanisms) as a potential therapeutic pathway which might be exploited by probiotics, antibiotics and pharmacobiotics. As Bested and colleagues highlight, a decade ago the notion that orally administered microbes could influence depression, anxiety or behavioral disorders was not something that would be taken seriously by more than a minority in the scientific community. With detailed historical analysis, they argue that such notions were too closely aligned with "autointoxication", or the modern interpretation of the term.
Time allows for the advancement of scientific technique and sometimes forces us to re-evaluate the past. In particular, the past can provide signposts to the future investigative pathways. Through the 3-part series the authors illustrate how contemporary investigations are providing some small degrees of validation to researchers who had reported, nearly a century ago, on areas such as diet and intestinal permeability, or fecal microbiota transfer. However, this is not the ultimate destination of the series. They make a clear case that history, from the days of Metchnikoff and autointoxication, is in many ways repeating itself (e.g. citing recent animal studies on probiotics for longevity and urine analyses for uremic toxins linked to personality). With the historical aspects in place, the authors make a strong plea to international researchers from various disciplines to raise the stakes – move the research toward the clinic and consider the context of the real-world setting of the lifestyle and dietary habits, and how these might interact with gut microbes in those with depression and other mental health disorders. Bested and colleagues are not underestimating the critical value of pre-clinical work that has served to formally place the topic on the agenda, they are simply stating that it is time to funnel all this work and begin an exit strategy from phase I of translational medicine.
The future of this area, gastro-biological psychiatry as they refer to it, is very bright. Logan recounts his experience during one of the breakout sessions at the International Probiotics and Health: Biofunctional Perspectives symposium in Montreal, Canada in 2002. Raising the notion of probiotics as possibly being relevant to mental health, he was literally laughed at. Even at a conference dedicated to the value of probiotics in human health, it was a bit too much. A decade later, with massive amounts of research still to be done, the gut-brain connection as mediated by microbes and its relevance to mental health no longer seems to be a laughable matter. Earlier this month, Kirsten Tillisch and colleagues published a landmark paper in Gastroenterology showing evidence of brain activity modulation by a probiotic containing fermented milk drink (4).
This said, the curiosity on the issue will be there for some more years to come and we see that as an asset for Gut Pathogens to emerge as a preferred medium and prestigious platform to foster dialogue and discussion. Certainly, this will be augmented by continued submissions in the area of gut-brain axis; in particular, more mechanistic studies.
1: Bested AC, Logan AC, Selhub EM. Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part I – autointoxication revisited. Gut Pathog. 2013 Mar 18;5(1):5. [Epub ahead of print] PubMed PMID: 23506618.
2: Bested AC, Logan AC, Selhub EM. Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part II -- contemporary contextual research. Gut Pathog. 2013 Mar 14;5(1):3. [Epub ahead of print] PubMed PMID: 23497633.
3: Bested AC, Logan AC, Selhub EM. Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III -- convergence toward clinical trials. Gut Pathog. 2013 Mar 16;5(1):4. [Epub ahead of print] PubMed PMID: 23497650.
4: Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain-Raspaud S, Trotin B, Naliboff B, Mayer EA. Consumption of Fermented Milk Product with Probiotic Modulates Brain Activity. Gastroenterology. 2013 Mar 5. doi:pii: S0016-5085(13)00292-8. 10.1053/j.gastro.2013.02.043. [Epub ahead of print] PubMed PMID: 23474283.