Of Bugs and Men

Gut microbiota, brain functions and the susurrations of a new discipline, ‘Gastro-biological psychiatry’

Gut Pathogens Editorial — Wed, 20 Mar 2013 17:20:11 +0000

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) 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.

References:

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.

Gut Pathogens calling for your Genome Announcements

Gut Pathogens Editorial — Tue, 08 Jan 2013 17:35:50 +0000

Gut Pathogens is now accepting submissions of Genome Announcements – articles giving a brief and concise account of a complete or partial genome of a gut pathogen or probiotic organism.

Gut Pathogens, which received an Impact Factor of 2.11 this year, is truly an international journal and the ideal forum for the rapid and global dissemination of your Genome Announcement. The open access platform allows for greater visibility and the average time from submission to first decision is just 15 days.

Co-Editor-in-Chief, Professor Niyaz Ahmed, envisages the journal becoming ‘a single, specialized publication dedicated to covering both the biology and clinical microbiology of major bacterial and viral pathogens of threat to gut health.’

In addition, he foresees Gut Pathogens becoming a single niche journal for both the biology of probiotics and probiotic-interventions against pathogens.

Submit your Genome Announcement to Gut Pathogens today!

Dr Srimathy Sriskantharajah
Senior Journal Development Editor

Thanks to our reviewers of 2012

Gut Pathogens Editorial — Tue, 08 Jan 2013 16:57:43 +0000

We would like to thank all those fantastic people who volunteered to review contents for Gut Pathogens. These hundreds of generous souls devoted their precious time and intellect to assess, evaluate and in some instances, edit submissions. Without this support and timely efforts, Gut Pathogens would have not been able to keep its ‘submission to acceptance’ time of a little more than one month. Although we are not in a position to list all names, our reviewers come from many different countries and regions. Many of our own editorial board members served as referees on different occasions. Thanks to all, again.

Prospective genomics in epidemics – lessons from the German E. coli outbreak

Gut Pathogens Editorial — Sat, 23 Jul 2011 04:43:13 +0000

The Open Access biomedical journal, PLoS ONE recently published an article by Mellmann et al. entitled, Prospective Genomic Characterization of the German Enterohemorrhagic Escherichia coli O104:H4 Outbreak by Rapid Next Generation Sequencing Technology. The following is an opinion piece by Dr. Niyaz Ahmed, who works as a section editor for PLoS ONE and the academic editor of this paper. He is an expert in the area of molecular epidemiology and genomics of bacterial pathogens at the University of Hyderabad, India. As the subject of this blog is also of significant interest to the audience of Gut Pathogens, we are reproducing Dr Ahmed’s blog post hereunder [with thanks to PLoS ONE community blog, EveryONE) where the blog was originally posted.

When a monstrously virulent strain of never-before-seen E. coli suddenly appeared in Germany last month, the rush to decode became an immediate focus. Several groups became engaged simultaneously to crack the genome of the underlying bug and then followed a huge crowd-sourcing effort on the internet as soon as the genome sequences were made available. Given that reasonable data were made available by these authors within 60 hours of the outbreak, not much of the evolutionary history of the organism had been dissected and a great deal of the interpretation remained vague. An informed, scientific treatise was needed to help health control authorities and policy makers launch a serious mitigation campaign; this work, in that sense, constitutes the first official report on the genomic footprint of the underlying E. coli strain. The authors report chronological (step-wise) recombination of the genome in the outbreak strains over a period of ten years. This reveals the extraordinary capability of certain pathogens to recombine so that a devastating phenotype finally emerges with a multi-dimensional fitness advantage. Further, the study of Mellmann et al. demonstrates the might of present-day sequencing technologies such as Ion Torrent in enabling genome-guided epidemiology, diagnostics, and interventions.

I have no hesitation to say that the study carried out by Mellmann et al. is truly a technical masterpiece, a first time proof-of-principle, whereby, next generation sequencing could be harnessed in real-time when certain ‘gold standards’ such as serotyping failed miserably. This report has an important bearing on the new proposed field of ‘epidemic forecasting’ in which the spread potentials of a pathogen could be predicted based on genomic fingerprints – in other words, predicting if the infection will assume pandemic proportions. The finding that the E. coli strains analyzed were enteroaggregative (EAEC) could explain this. EAECs could persist in recovered or subclinical cases and that they could be carried by the latter on travel routes worldwide.

One of the possible shortcomings of the study could be that it is silent on the mechanistic details of ‘adornment’ of these bacteria with several layers of fitness – multiple antibiotic resistance, acid tolerance, enteroaggregative capacity and shigatoxin production all bundled up in one ‘naturally’ chimeric strain in just 10 years is extremely dramatic! The pace of evolution of the German outbreak strains has surpassed even Helicobacter pylori, an organism notorious for its speed of recombination, recasting its entire genome every forty years. We recently had an opportunity to sequence and look at H. pylori genomes hierarchically obtained across ten years. We did not find major insertion, deletion and substitution events.

Technology helped with the dissection of the E. coli epidemic in hours and days, but the editorial process also was seamless and prompt enough to enable rapid dissemination of results. Open and early access is very important for the dissemination of findings during epidemic times because much of the control and mitigation measures need planning in the light of latest research findings.

Gut Pathogens publishes its first metagenome article

Gut Pathogens Editorial — Wed, 06 Jul 2011 04:55:26 +0000

Metagenome of the gut of a malnourished child – Sharmila Mande and colleagues from India

Background

Malnutrition, a major health problem, affects a significant proportion of preschool children in developing countries. The devastating consequences of malnutrition include diarrhoea, malabsorption, increased intestinal permeability, suboptimal immune response, etc. Nutritional interventions and dietary solutions have not been effective for treatment of malnutrition till date. Metagenomic procedures allow one to access the complex cross-talk between the gut and its microbial flora and understand how a different community composition affects various states of human health. In this study, a metagenomic approach was employed for analysing the differences between gut microbial communities obtained from a malnourished and an apparently healthy child.

Results

Our results indicate that the malnourished child gut has an abundance of enteric pathogens which are known to cause intestinal inflammation resulting in malabsorption of nutrients. We also identified a few functional sub-systems from these pathogens, which probably impact the overall metabolic capabilities of the malnourished child gut.

Conclusion

The present study comprehensively characterizes the microbial community resident in the gut of a malnourished child. This study has attempted to extend the understanding of the basis of malnutrition beyond nutrition deprivation.

‘Indians could be refrectory to German EAEC outbreak strains’

Gut Pathogens Editorial — Tue, 05 Jul 2011 16:25:26 +0000

My friend, Lothar Wieler, called this evening from Berlin and informed that they are now tracing the history of the bacteria, and will be out in the field going after cows, trash and soil to know the natural descent of the outbreak strain! so that its kinships are established. This is now the natural scientific way out as the latest analysis released by the BJI indicates that the two German strains (01-09591 originally isolated in 2001 and TY2482 from the 2011 outbreak) have clonal profiles for all 12 virulence/fitness genes and 7 MLST housekeeping genes (100% identity). However, at some point over this 10-year period, the new 2011 outbreak strain might have accumulated mutations/plasmids that conferred ability to resist many additional types of antibiotics. In simple words, the source of the German EHEC outbreak is home grown – their own EAEC strain from a 2001 outbreak.

I am hopeful Lothar and his team will succeed in their efforts. We discussed also the possibility that the new isolate being interoaggregative could become pandemic if certain patients turn chronic carriers and could take the bug with them on travel routes. The EU therefore should be proactive on containment of this outbreak within the boundaries of Germany. Lothar, (who is always surprised and amused on visibly unhygienic conditions in certain parts of India, such as heaps of garbage, open drains etc., and apparently healthy people with no institutionalized outbreaks! ) then laughed loud to say Indians could actually be immune to the EHEC like strains – so no worries!! and, I agree. So sometimes the cow dung around us could be ‘auspicious’ in many ways!