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How close are microbiome-modulating therapies that target the brain? A quick overview of the evidence

Debate exists about how soon knowledge about the gut-brain axis will bear fruit. Yet the microbiome-gut-brain axis is a hot topic of scientific investigation and several companies around the globe are actively pursuing gut microbiome therapies that focus on brain-related conditions.

Here’s a quick overview from our lab scientists on various areas of brain health and the evidence linking each one to the gut microbiota.

General early life neurodevelopment

Dozens of human studies and mechanistic animal studies support the relevance of gut microbiota to normal behaviour and neurodevelopment; however, these studies are not always specific to neurological development, and the observed effects could be confounded by many other factors that affect the early life microbiome.

Autism spectrum disorders

Although there are known genetic contributors to autism spectrum disorders, both human and animal studies show a connection between gut microbiota and both gastrointestinal symptoms and social deficits in these individuals.

Anorexia nervosa

A moderate level of evidence links anorexia with gut microbiota; no mechanistic studies have been completed to date.

Attention deficit hyperactivity disorder (ADHD)

A low level of evidence implicates gut microbiota in ADHD; this disorder may also be linked to diet, but much more research needs to be undertaken.

Multiple sclerosis

A growing number of human studies as well as mechanistic animal studies have found the gut microbiota has immunomodulatory effects that may affect multiple sclerosis (MS) disease progression. Transfer of the microbiota from a human with MS to a mouse increases MS-like symptoms.

Post-traumatic stress disorder (PTSD)

Moderate evidence and one human study connects the gut microbiota with PTSD; further research may explore the mechanistic role of chronic inflammation as well as cortisol and dopamine regulation.

Depression

A high level of evidence links gut microbiota with depressive symptoms; probiotics may improve depression in both humans and animals.

Anxiety

While the studies on anxiety overlap with those on depression, some reports in both animals and humans show potential of microbiota modulation — for example, through probiotics — for improving symptoms of anxiety.

Fatigue

Extreme fatigue may also be linked with the gut microbiota, although diet appears to be a major confounding factor and more research is required.

Parkinson’s disease

Many studies in humans link Parkinson’s disease (PD) with the gut, but chronic constipation in those with PD is a possible confounding factor. Mechanistic evidence to back these findings is just beginning to emerge.

Alzheimer’s disease

Emerging evidence shows the Alzheimer’s-gut connection: in mice, Alzheimer’s-like symptoms are altered by microbiome manipulation.

A round table discussion at the Global Engage Microbiome R&D and Business Collaboration Forum on Thursday, November 2nd, led by CEO Malcolm Kendall, will explore what we know about the gut-brain axis and how soon it could yield breakthrough therapies.

microbiome insights CEO
CEO Malcolm Kendall

About the company

Microbiome Insights provides state-of-the art microbiome analysis and bioinformatics.

Our end-to-end service starts with experimental design and sample collection and extends to data analysis and bioinformatics interpretation.

Microbiome Insights is focused on providing our clients with a deeper understanding of functions and interactions of microbial communities across a range of human, animal, agricultural, and environmental research applications. Our team of experts and testing methods combine to provide fast, dependable, cost-effective results with highly comprehensive, publication quality bioinformatics. To learn more, see here.

From the human genome to the human microbiome: Toward clinical applications

Genetics versus Genomics

In 1991 the Human Genome Project—a collaborative effort to map the whole human genome—was established. A 5-year plan was put in place addressing the initial framework for the efforts including reliable testing methods, validated protocols, and milestones along the way. This marked a different path from previous studies of genetics—that is, the study of genes, or rather the identification of a particular gene that may be instrumental in a phenotypic outcome. Much of the work in this field had previously been exploratory in nature, with a growing body of evidence linking certain genetic variations or single nucleotide polymorphisms (SNPs) to disease states.

In mid-2000 it was announced that the Human Genome Project had published their results of the almost completely sequenced human genome. While the results were interesting, the data were a far cry from being applicable. What it did do was spur further interest in developing better technologies that would allow cheaper and faster sequencing to add onto these initial findings.

In the years spanning 2004 to 2014 a multitude of companies were competing to churn out faster and better technologies such as the Roche 454 and the Illumina sequencing systems. The technologies were proving to be advantageous in many ways; for example, iterations of these technologies were serving to advance the microbiological sciences.

DNA samples are loaded to 96-well plate for PCR analysis

Awareness of the Microbiome

While the whole genome studies were mushrooming during this decade, the study of microbes was still largely based on culture dependent techniques and there was very little information or interest in communities of microbes residing in the body. Basic microbiology was built on the identification of single pathogenic microbes that were instrumental in disease states, while the non-pathogenic microbes were believed to lie dormant. However, certain areas of research focused on how microbes might influence host, or vice versa.

It was becoming widely accepted that microbes in the gut had a part to play in localized gut related diseases such as Crohn’s but it was less understood how the commensal bacteria shifted in abundance, and what caused these ideal growth conditions. This curiosity began to blossom, largely due to the advances in technology brought about by the human genome project, that would allow these growing questions (and concerns) to be addressed affordably and quickly. In 2007 the Human Microbiome Project was born.

“The recent emergence of faster and cost-effective sequencing technologies promises to provide an unprecedented amount of information about these microbial communities, which will bolster the development and refinement of analytical tools and strategies.”

– NIAID Director, Anthony S. Fauci

Microbial Snapshots

Once it was established that the microbiome was of interest, and of importance to the host, researchers developed new methods for studying it by taking advantage of the high throughput sequencing technologies that came to market during the genomics boom. First amplicon sequencing methods and later shotgun metagenome methods were the gold standard in microbiome research. But scientists began to acknowledge several factors as information about different ecosystems was being compared; first, that microbiomes were specific to their locations and diverse in nature, making them quite different from one body site to another. This was a paradigm shift as many had not considered this level of diversity in commensal and pathogenic bacteria, but also as compared to receiving the same genetic information from every host cell regardless of its location in the body. Secondly, the microbiomes are ever shifting and, upon collection, must be stabilized in such a way that the ‘snapshot’ is maintained at time zero. This means that factors such as temperature and moisture could quickly change a microbial profile if the sample is not treated with care. This opened the doors to a wide variety of collection devices and stabilization buffers with specific media to help maintain these profiles while being interoperable to laboratory procedures.

Clinical Applications

We already see clinical and diagnostic applications for microbiome findings. Although we are still working towards scientifically validating these applications we seem to be on a similar trajectory as we saw with genomics research in terms of diagnostic applications, publications, and consumer-friendly offerings. Interestingly, a singular ‘omics’ (i.e. proteomics, metabolomics, genomics, microbiomics) is informative on its own, but combining multiple features to define functionality of systems in the body will prove to be more fruitful in the long run. Understanding the complex nature of these systems and how they interact will enable us to see how changes or shifts in one system can have effects in other systems. This multi-omics approach is the basis for personalized medicine and furthermore can apply in other domains such as plants, animals, and environmental ecosystems.

At Microbiome Insights we are working with researchers to elucidate synergistic effect of multiple ‘omics’ at work. With this approach we are focused on the skin microbiome, the gut-brain axis, pharmacology, and other areas of science that bring together the genome and microbiome for a better understanding of human health.

About the company

Microbiome Insights provides state-of-the art microbiome analysis and bioinformatics.

Our end-to-end service starts with experimental design and sample collection and extends to data analysis and bioinformatics interpretation.

Microbiome Insights is focused on providing our clients with a deeper understanding of functions and interactions of microbial communities across a range of human, animal, agricultural, and environmental research applications. Our team of experts and testing methods combine to provide fast, dependable, cost-effective results with highly comprehensive, publication quality bioinformatics. To learn more, see here.

Microbiome Research: Don’t Forget The Fungi

Microbial Interactions In Living Systems

The emerging field of the microbiome is in pursuit of understanding the microbe-microbe and microbe-host interactions that occur in virtually all living systems. This includes interactions critical to plant and animal health. The fundamental question is: What role(s) do the microbes and their functions play in broader systems?

Advancements in technology, such as next generation sequencing, have allowed us to overcome the barriers of culture-dependent methods of identification and classification, providing the ability to sequence and identify a more complete community of microbes in any given sample with a high degree of sensitivity and reproducibility.

It seems, however, that the term ‘microbiome’ tends to implicitly refer to commensal and pathogenic bacteria, with very little attention paid to the role of eukaryotic organisms. As such, the field is heavily utilizing 16S amplicon sequencing to increase our understanding of these bacteria. But what about other amplicons such as 18S or ITS (internal transcribed spacer) that shed light on eukaryotic or fungal communities?

The Mycobiome

In recent years, there have been more published data elucidating the presence and contribution of fungi in certain disease states. These fungi have been shown to interact with bacterial communities in either a synergistic or competitive manner. In either relationship, these fungi may be a critical component of the progression of such diseases—including hepatitis B, cystic fibrosis, and even inflammatory bowel disease. As a result, researchers have coined the term ‘mycobiome’ to refer to the communities of fungi that may play an interesting role in the system.

The human body is a unique ecosystem, and we have long known mucosal sites are abundant with fungal flora.  What we are beginning to identify is how these communities interact with other sites across the body, where bacterial communities reside. Besides the specific diseases associated with fungi, we are seeing evidence that overall gut health is maintained by a degree of fungal-bacterial interaction. Mechanistically, the mycobiome appears to play a role in inflammation and metabolism by modulating the bacterial microbiome.

Environmental microbiomes are also of growing interest in the microbiome field, with a particular focus on ocean microbiomes, air pollutants, and soil microbiomes. In soil microbiomes, where fungi are prevalent, researchers are interested in certain subcategories; studies focus on the soil microbiome, the plant/rhizosphere microbiome, or the point at which these two microbiomes interact, which is called the mycorrhizosphere. The fungal component of these microbial communities plays a critical role in the nutrition and growth of plants as well as in the exclusion of plant diseases. Mycorrhizal fungi have even been shown to mediate signaling between plants.

Amplicon Sequencing: 16S, 18S, & ITS

Unlike other next generation sequencing labs that have exclusively focused on the approaches of molecular biology and genomics, Microbiome Insights also pulls from expertise in microbial ecology and infectious disease to provide a more complete picture of the ecosystem. We have implemented standardized protocols for 16S (Prokaryotic) sequencing and have developed robust workflows for both 18S (Eukaryotic) and ITS2 (fungal) sequencing using the Illumina Miseq.  We apply these approaches as necessary to address specific scientific questions, and can build on this data using shotgun metagenomic sequencing. Altogether our expertise allows us to provide our customers with a full suite of tests—without forgetting the fungi.

About the company

Microbiome Insights provides state-of-the art microbiome analysis and bioinformatics.

Our end-to-end service starts with experimental design and sample collection and extends to data analysis and bioinformatics interpretation.

Microbiome Insights is focused on providing our clients with a deeper understanding of functions and interactions of microbial communities across a range of human, animal, agricultural, and environmental research applications. Our team of experts and testing methods combine to provide fast, dependable, cost-effective results with highly comprehensive, publication quality bioinformatics. To learn more, see here.

New Microbiome Insights Technical Blog

Microbiome Insights is pleased to announce that our team is getting ready to launch our own technical blog on microbiome science. The blog, written by our in-house experts who are leaders in the field, will focus on different microbial workflows and protocols, as well as commonly asked questions from the market.

The aim of our new blog is twofold:

(1) To discuss issues in standardizing protocols across labs focused on microbiome research

and

(2) To share our perspective on technical issues we encounter in our own work

We look forward to sharing and learning about state-of-the-art methods in microbiome research.

Contact us if you have a question you’d like to see addressed on our technical blog: info@microbiomeinsights.com