The question of what it means to be human is proving to be increasingly complex. It is thought that the human body is comprised solely of eukaryotic cells, those cells belonging to the host; however, this is not the case.

The human microbiome is the collective genetic material of microbes, which consist of bacteria, fungi, protozoa and viruses. Since humans and microbes have co-evolved in a symbiotic relationship, these microorganisms inhabit nearly every part of the human body, including the mouth, gut, nose and skin.

Within each human, there is a universe of living microorganisms so abundant that individuals contain more microbial cells, cells belonging to the microbiome, than they do their own. These bacterial cells have a larger impact on health and neural function than ever considered in the past. 

Historically, microbiota have been considered malevolent due to their role in human pathogenesis, the development of disease. Contrarily, the human microbiome benefits its human host by providing many functions that, despite being essential for survival, humans could not perform alone. 

“Pathogenesis is not the most common interaction that we are having with microbes, it’s probably the most rare,” said Dr. Timothy Sampson, an Assistant Professor in the Department of Physiology at Emory University.

Although these microbes can become disease-causing, they generally coexist symbiotically with the host organism. The microbiome’s importance cannot be overstated; it is often considered a supporting organ for its integral role in promoting smooth bodily functions. 

“There’s a huge genetic and metabolic potential for interactions [between the microbiome and the host]. [Those interactions are] happening constantly for the duration of our lives and are so essential for our health,” Sampson said.

The human digestive tract — the gut — is home to the largest microbial community within the human body. Because of its role in human health, human nutrition and metabolism, the gut microbiome is the epicenter of recent biomedical research. 

“The microbiome field really came to the forefront in the mid-2000s, because the genetics and genomics being used to sequence the human genome could be used to probe bacterial communities without having to culture them,” said Dr. Joseph Petrosino, the director of the Center for Metagenomics and Microbiome Research at Baylor College of Medicine. “With that tool in hand, that really was a renaissance for the microbiome field.”

Research reveals a correlation between the dysbiosis, or imbalance, of the gut microbiota and the pathogenesis of multiple diseased states. A study by Dr. Magnus Simrén, a Professor of Gastroenterology at the University of Gothenburg, demonstrated a correlation between the microbiome and the development of irritable bowel syndrome (IBS). 

The findings of studies such as these indicate that altering the microbiome may be a potential treatment for such diseases or disorders.

 “Many studies have shown that the microbiome has a role in the disease process itself,” Petrosino said. “And that then becomes a target that can be used to diagnose and treat a disease.”

Recently, an intersection between the central nervous system (CNS), composed of the brain and spinal cord, and the gut microbiome has been revealed. In a TedX Talk, Elaine Hsaio, a UCLA Associate Professor in the Department of Integrative Biology and Physiology, stated that complex behaviors including mood and emotion, learning and memory and anxiety can be connected to the gut flora.  

In a paper titled The Central Nervous System and the Gut Microbiome, Dr. Sarkis Mazmanian, a Luis B. and Nelly Soux Professor of Microbiology at the California Institute of Technology, follows the microbiome’s impact throughout human development. In this paper, he compiles multiple studies in a discussion about the correlation between the microbiome and neurodevelopmental and mood disorders.

“Animal models appear to show us that many behavioral disorders [may] have a link to the gut, ranging from anxiety, depression, autism and schizophrenia,” said Mazmanian, “[likewise with] neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease.”

A paper by Shelly Buffington, now an Assistant Professor in the Department of Neuroscience, Cell Biology, & Anatomy at The University of Texas, and Mauro Costa-Mattioli in the department of Neuroscience at Baylor College of Medicine demonstrated a significant relationship between gut microbiome dysbiosis with social defects in an Autism Spectrum Disorder (ASD) mouse model. A single bacterial strain, L. reuteri, was found to be missing in the microbiome of mice exhibiting behavioral deficits associated with ASD. Through the re-introduction of L. reuteri, behavioral deficits in those mice were selectively restored.

Another study by Hsaio, found strong associations between the gut microbiome and ASD. This study similarly found that there were 67 microbial species that differed between mice displaying symptoms related to ASD and mice who did not exhibit ASD-like symptoms. This study appeared to establish a causal relationship between the gut microbiome and communicative and sensorimotor deficits.

“People generally tend to think that the brain is autonomous,” Mazmanian said. “It was, and still is, far fetched that simple organisms like bacteria can modulate something as complex as the human brain… that something so foreign like a microbe could have such a significant impact on human biology.”

According to Hsaio, the microbiome’s effect on neural health holds the potential to create personalized, non-invasive and long-lasting treatments for diseases and disorders that are otherwise currently untreatable. Hsaio also states that, in regard to brain disorders, the clinical presence of microbial-based treatments is still far in the future, but today, microbial treatments are already being utilized for problems relating to the immune system and the gastrointestinal tract.

“There is still a lot of work that needs to be done for us to fully understand how impactful the gut and gut microbiome are to brain development and function,” Mazmanian said. “[Recent research] suggests that gut-brain connections are critical for health, but we still don’t know the full [scope] of its importance.”

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