Inside of you there are 10¹³ human cells and 10¹⁴ bacteria cells.

In other words, for every one cell of you there are ten that are not you…Wait, what? The first question this recent discovery may fuel is a stumbled WHAT? But lets digress for a moment and ask, why?

The initial visceral curiosity here arises from one major assumption that the Western psyche makes about the world, that I am an individual and am derived in my current form from the process of competitive selection. The reality however, is that none of us are individuals and we are all derived not just from natural selection, but from collaborative efforts between tens of thousands of species of organisms acting in symphony to produce the emergent concert that is: us. That may be a bit heavy. Let me explain.

Again, there are ten times the number of bacterial cells throughout the human body and they are mostly centralized to the digestive tract. This internal ecosystem of microbial flora is referred to as one’s “microbiome”. Each person’s microbiome is different, in a similar way that we are all different. The distribution of species in the digestive tract reflects one’s life experiences, adventures and location of upbringing. For example, the typical gut flora of a person raised in the United States has more bacteria specialized in processing fat and protein. This is in part why people immigrating to the United States often have problems with gaining weight in the first few years, because their microbial counterparts are ill-equipped at handling the amount of fat in American foods.

Another astonishing example of this “microbial footprinting” is in the microbiomes of people who have lived their entire lives in Japan where seaweed is a dietary staple. Throughout the world the microbe Bacteroides plebeius has been observed in the gut of various people. Curiously however, the B. plebeius microbe in some Japanese people has incorporated a gene passed to it, via horizontal gene transfer, from Zobellia galactanivorans, a marine bacterium. The gene in the Japanese form of B. plebeius expresses enzymes specializing in the degradation of certain polysaccharides found in seaweed. Implications for the exhausted “Nature vs. Nurture” debate abound, these findings are Earth-shattering in more ways than the hands can hold. Oh, by the way, this doesn’t stop at digestion.

Bacteria Are Everywhere in the Human Body

The real sexy aspect of this new vein of research is the implications for the behavioral sciences. In 2011, a series of papers came out linking a lack of adequate gut microbial populations to an anxiety disorder. Researchers raised a brood of mice in a germ-free environment, i.e. from birth they had little to no exposure to the typical microbial populations they may encounter, and the results were a bit unsettling. The researchers noted significant defects in the development of the Amygdala which subsequently showed in behavioral studies that the sterile mice had major issues with anxiety and depression. In another similar study, it was shown that feeding normal mice probiotic bacteria significantly reduces depression-like behavior.

Right now, this is the biggest emerging area of research worldwide. Finally, the notion that we are not individuals, but emergent structures of ecosystems is taking hold. The result of such novel understanding is entirely uninformed and preemptive attempts at targeting this new world to cure and change. Currently, probiotic medicines are starting to crop up, each of which will soon be shown to have more “side effects” than efficacy in the expected. When we make a discovery, we immediately assume we understand how to manipulate the system, unaware of how the vastly complex structures we are changing. We are always confidently overzealous. These recent discoveries are awesome, they really are, but I want to stress that we cannot let our zeal overtake us. This time around, we must admit a lack of understanding and re-realize the feeling of awe. Again, upwards of 40,000 different species of bacteria, right inside of you, are talking to one another; buffering carcinogens and reward hormones, digesting cellulose, fermenting, interacting in ways we really will never know although they may be helping “us”!

“We” would not be alive if it were not for our microbial brethren. Let me pose this question: Is taking the step to understand this internal ecosystem the next step in consciousness. Until now, we have had a very elementary understanding of who we are and why we are who we are. Is this the next step?

- Jesse Bryant

Animals in a microbial world, a new imperative for the life sciences – McFall-Ngai et al. 2012 PNAS

Mood and gut feelings – Forsythe et al. 2009 Elsevier

An ecological and evolutionary perspective on human-microbe mutualism and disease – Dethlefsen et al. 2007 Nature

The gastrointestinal (GI) tract in humans provides a home for many (10¹⁴) bacterial organisms. The colonization of the GI by bacteria, or microbiota, starts at birth and continues throughout early development and life. These microbiota affect many bodily functions, aiding metabolism, modulating inflammation, and defending against harmful micro-organisms. Each person has a unique profile of microbiota, which is influenced by genetics and the environment. Healthy people, however, generally have similar numbers and distributions of microbiota. Interestingly, disorders of the GI tract have a high comorbidity with mental illness.

It is not surprising then that research in this field has grown, with labs hoping to gain a better understanding of the ‘gut-brain-axis.’ If these labs can elucidate the effect of microbes in the GI tract on the central nervous system, they could shed light on why more than half of patients with irritable bowel syndrome meet the criteria for mood disorders, or how GI tract disorders and mental illnesses can be more effectively treated.

Many researchers are currently focusing on how variations in the composition of microbiota impact physiology and contribute to disease, such as obesity and inflammation. Increasingly, studies have been revealing that these microbiota communicate with the brain and influence its function and behavior, potentially by neural, endocrine, and immune pathways.

In 2010, Jane Foster and colleagues at McMaster University in Ontario found that microbiota may affect gene activity during central nervous system development. They compared how germ-free and normal mice act on an

Elevated plus maze used for testing anxiety-like behaviors in mice (from the Mouse Phemone Database)

elevated plus maze (shown to the right) that is used for testing anxious behaviors. Normally, mice avoid areas they might be seen and spend more time in the less visible arms of the maze.

While the normal, control mice did spend more time in the ‘closed’ over ‘open’ arms, germ-free mice spent more time in the open arms, exploring them and showing less anxious behaviors. After the experiment, Foster and her team examined the brains of the mice and found alterations in the gene expression levels of several genes in the germ-free mice, particularly in those affecting brain-derived neurotrophic factor (BDNF) and serotonin (5HT). BDNF and 5HT had been previously suggested to affect emotion and anxiety.

Importantly, the study shows that the absence of microbiota can alter behavior and suggests that the microbiota in the GI may impact gene expression during the sensitive period of early brain development. Although studies in mice need to be proven translatable to humans, a pediatrician was interested in collaborating with Foster to determine if he could determine a way to fix the microbiota profile of some of his patients before puberty.

Using germ-free animals and animals exposed to infections, researchers have suggested a role for microbiata in regulating mood, anxiety, cognition, and pain. More research is needed to decide whether formulating or modifying gut microbiota could serve as a possible therapeutic for central nervous system disorders. Foster suggests combining preclinical work on microbiota with clinical work on the impact of antibiotics and probiotics on brain development and function. This could allow researchers to better understand bottom-up control and provide inspiration for novel interventions in mental illness. In the end, communication between scientists and clinicians in various fields and domains is crucial to determine the relationship between gut microbiota and the central nervous system.

Sources:

Microbes Manipulate Your Mind – The Guardian

Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour – Nature Reviews Neuroscience

Effects of gut microbiota on the brain: implications for psychiatry – Journal of Psychiatry and Neuroscience

Reduced anxiety-like behavior and central neurochemical change in germ-free mice – Neurogastroenterology and Moltility