Illustration by Benjamin Arthur for NPR

The mammalian gut is host to a wide variety of microbiota that are key to healthy metabolism. Beginning from early periods in mammalian life, these protozoa, archaea, eukaryotes, viruses, and bacteria colonize the mammalian gut, forming a symbiotic relationship that lasts through the organism’s life cycle.

With the advent of genetic tools, computational power, and sequencing technologies, researchers have been able to dive deeper into understanding individual microbial communities. Through collaborative efforts, projects such as the Human Microbiome Project (HMP) and the Human Gastrointestinal Bacteria Genome Collection (HGG) have developed reference genomes cataloging microbial communities of healthy individuals across different sites on the human body: nasal passages, oral cavity, skin, gastrointestinal tract, and urogenital tract. Within humans, these microbiota number on the order of 1013- 1014 cells, composed of the bacterial phylums Firmicutes, Bacteroides, Proteobacteria, Actinobacteria, Fusobacteria, and Verrucomicrobia. Firmicutes and Bacteroides are by far the most predominant, occupying around 90% of the gut microbiome [2].

This is not to say changes do not occur in the composition of the microbiome. Rather, microbial communities are dynamic especially in childhood, changing at different time points in an individual’s life span. These changes are largely dependent on environmental factors. Microbial colonization of the gut begins shortly after birth, with the microbiota composition dependent on the mode of delivery and feeding[2, 3]. Vaginally delivered infants share a higher proportion of gut microbiota 16S rRNA gene sequences to mothers as compared to those delivered through Caesarean section (C-section). This is due to the fact that vaginally delivered infants are exposed to maternal fecal and vaginal bacteria while C-section infants acquire microbes from the skin and hospital environment. Interestingly, C-section displays a decrease in microbiota diversity, delay in colonization of Bacteroides, and has been associated with an increased likelihood of developing allergies and asthma. Other factors influencing the diversity of the microbiome in this early developmental stage include whether the infant is breast-fed or formula-fed, antibiotic usage, genetics, and geographical location.

The overall composition of intestinal microbiota of infants is largely characterized by Proteobacteria and Actinobacteria, increasing in diversity and converging towards predominantly Firmicutes and Bacteroides phyla as the infant progresses to adulthood. However, once the microbiome is well established, it takes on a general core composition within an individual. It has further been suggested that different individuals retain a “core microbiome”, composed of a similar set of microbial genes that may be encoded by different microbial species [5]. Metagenomic studies in identical (or monozygotic) and fraternal (dizygotic) twins additionally have shown that individuals from the same family display more similar 16s rRNA sequences than unrelated individuals, with no significant differences in bacterial diversity between the two types of twins. However, other studies have shown that monozygotic twins demonstrate the highest similarity in the bacterial species present in their microbiota, suggesting that the host genome influences its composition.

Regardless of differentiations in microbiota between individuals, gut microbiota in most individuals generally remain stable for a significant period upon reaching adulthood. This stability is essential for the symbiotic relationship between host and microbiota. Gut microbiota play an important role especially in digestion and metabolism, as the microbiota can “make up” for metabolic pathways not explicitly present in the mammalian genome, thereby increasing our ability to digest compounds and extract energy [1]. Additionally, a stable microbial ecology is essential for immune health, as disruptions can cause the host to be susceptible to infection and diseases including inflammatory bowel disease (IBD) and celiac diseases [6].

Interestingly, the gut microbiome retains a certain degree of plasticity and can change in response to exogenous factors [1]. Diet and antibiotics can play a role in changing the composition of the microbiome, albeit with largely short-term effects [4]. This gut microbiome is therefore a living and dynamic entity, subject to fluctuations in diet, environment, and health — both physical and mental.

One of the simplest and most influential causes for changes in the intestinal microbiota of infants is the general process of aging. As infants grow and begin to consume different foods and develop a specific diet, the gut microbiota becomes increasingly unique to each individual. While this process of aging is universal to everybody’s health and their stomach microbiome, further factors exist that can influence gut microbiota as well — one of the more notable ones being mental health.

The Stomach-Brain Connection

Stomach health and mental health have more connections than we assume, mostly attributed to our gut microbiome. Feelings like “gut-wrenching” experiences as well as “butterflies in your stomach” are not just expressions used to describe general feelings of anxiety, but actual, physical sensations that can influence how our brains think and function.

For infants, this means that general feelings of anxiety, or adverse life experiences can determine the physical health of their stomach for the rest of their lives. High scores of early adverse life events (EALs) — including events such as physical, emotional, or sexual abuse, illnesses, substance abuse, or general trauma — have a strong positive correlation with higher stomach and gut discomfort in both men and women over the age of 18. Most specifically, this stomach pain came in the form of Irritable Bowel Syndrome (IBS), with there being a significant association between prevalence and symptom severity [7].

Among these correlations, further evidence of the gut-brain connection exists in the influence that the stomach microbiome has on a multitude of neurodevelopmental, depression, anxiety, and attention disorders. For example, a large number of children diagnosed with ADHD similarly have serious stomach or bowel issues through the form of gastritis or stomach ulcers, as well as other gastrointestinal issues [7]. This connection between the two organs shows the significant effect that mental health has on the physical body — and vice versa.

Some of these findings may come off as obvious: suffering from a chronic condition such as IBS is bound to have stressful effects on one’s mental health, and constant anxiety and other worrying symptoms can lead to feelings of nausea or unease. However, these specific examples bring about easier methods to learn about the specific bi-directional pathway present between the body and the brain, and in the future, connect it to countless other patterns.

The microbiome of the stomach communicates with the brain through the body’s Central Nervous System (CNS), the body’s primary method of controlling both bodily and mental functions through the brain and the spinal cord. Utilizing both neural and endocrine pathways to communicate and cooperate, this physical connection between the stomach and the brain is commonly referred to as the gut-brain axis (GBA), demonstrating how the different neural and chemical signals that are sent to the brain from the gut result in the brain’s elevated stress responses or other reactions. Even other physiological structures, thickness of myelin sheaths, or the length of dendrites are determined and manipulated by several factors, including the types of microbiota present in the stomach, and their health [8]. And as we grow older, the impacts of these different microbiota become even clearer.

Source: Nature

As mentioned before, the process of aging is the primary factor in gut microbiome development. Growth and development of the human body over a period of time inevitably causes the stomach’s microbiota to drift in composition, slowly moving towards a more unique makeup for each individual. This microbiotic makeup can differ for each person, depending on their personal history, mental health, and even their daily diet. Each factor of human growth determines the health and state of the stomach’s microbiota, and by extension, human health.

Aging and survivability in humans is a constant endeavor that we are still continuing to explore. So many different factors and possibilities exist that make it more and more difficult by the day to determine what can keep us perfectly healthy, or elongate our current lifespan — with our understanding of the gut-brain axis being just the beginning. Researchers, nutritionists, and chemists around the world are actively dedicating time and resources to better understand the intricacies of the gut microbiome, and there is much potential to be found in using newfound knowledge to improve human life. By understanding the different species of bacteria found in the stomach that contribute to mental health issues, or vice versa, we may even be able to find new methods to significantly curb detrimental symptoms of mental illnesses, such as ADHD, depression, or more.

Supplement companies have already proven how research into this area can bear fruit, particularly with probiotics — live bacteria and yeasts that can help boost the health of your gut microbiome — and their assistance in the gut-brain axis. They come in the form of yogurt, sauerkraut, and kombucha, and increase the amount of beneficial bacteria in your stomach to help boost your gut, and mental health in response.

Source: Lallemand Animal Nutrition

These supplements aren’t complete replacements for normal medications. Typical prescriptions of antidepressants, diarrhea medicines, and more are still required, but probiotics can provide an incredibly effective boost when paired with typical treatment levels.

The stomach is also referred to as our “second brain” for good reason. The health and microbiome of the gut is tightly interwoven into the wellbeing of our brain, physical state, and mental state, and oftentimes issues with our daily moods or dispositions can easily be attributed to the state of our stomach.

Just remember: if you think everybody hates you, you probably need to sleep. And if you think you hate everybody you probably just need to eat.

Citations

  1. Metcalf, Jessica L, Laura Wegener Parfrey, and Rob Knight. “Defining the Human Microbiome.” Nutrition Reviews 70 (August 1, 2012): S38–S44. https://doi.org/10.1111/j.1753-4887.2012.00493.x.
  2. Rinninella, Emanuele, Pauline Raoul, Marco Cintoni, Francesco Franceschi, Giacinto Miggiano, Antonio Gasbarrini, and Maria Mele. “What Is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases.” Microorganisms 7, no. 1 (2019): 14. https://doi.org/10.3390/microorganisms7010014.
  3. Rodríguez, Juan Miguel, Kiera Murphy, Catherine Stanton, R. Paul Ross, Olivia I. Kober, Nathalie Juge, Ekaterina Avershina, et al. “The Composition of the Gut Microbiota throughout Life, with an Emphasis on Early Life.” Microbial Ecology in Health & Disease 26 (2015). https://doi.org/10.3402/mehd.v26.26050.
  4. Singh, Rasnik K., Hsin-Wen Chang, Di Yan, Kristina M. Lee, Derya Ucmak, Kirsten Wong, Michael Abrouk, et al. “Influence of Diet on the Gut Microbiome and Implications for Human Health.” Journal of Translational Medicine 15, no. 1 (April 8, 2017). https://doi.org/10.1186/s12967-017-1175-y.
  5. Turnbaugh, Peter J., Micah Hamady, Tanya Yatsunenko, Brandi L. Cantarel, Alexis Duncan, Ruth E. Ley, Mitchell L. Sogin, et al. “A Core Gut Microbiome in Obese and Lean Twins.” Nature 457, no. 7228 (November 30, 2008): 480–84. https://doi.org/10.1038/nature07540.
  6. Zheng, Danping, Timur Liwinski, and Eran Elinav. “Interaction between Microbiota and Immunity in Health and Disease.” Cell Research 30, no. 6 (May 20, 2020): 492–506. https://doi.org/10.1038/s41422-020-0332-7.
  7. Ming, Xue, et al. “A Gut Feeling.” Child Neurology Open, vol. 5, 2018, doi:10.1177/2329048x18786799.
  8. Skonieczna-Żydecka, Karolina, et al. “Microbiome — The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health.” Journal of Clinical Medicine, vol. 7, no. 12, 2018, p. 521., doi:10.3390/jcm7120521.

This article was written by Lilian Zhang, who is a junior undergraduate student at UC Berkeley studying Chemical Biology, and Iris Lu, who is a sophomore undergraduate student at UC Berkeley studying Integrative Biology. This article was edited by Oliver Krentzman, a senior undergraduate student at UC Berkeley studying Cognitive Science.

We write on psychology, ethics, neuroscience, and the newest in neural engineering. @UC Berkeley

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