Introduction
This thesis presents a review of contemporary literature and research on the connections between humans’ gut microbiota and brain, and the resulting psychopathological implications of these connections–especially when they go awry. Our gut microbiota, which is comprised of bacteria, archaea, fungi, and viruses, is intricately connected to multiple aspects of life: most obviously our physical health, from obesity to immune deficiencies to allergies, and less obviously, our mental health, such as mood disorders, anxiety, thought disorders, and general social behavior. This relationship is dynamic, operating in both direct and indirect ways, and is active from prenatal development through to death.
In this thesis, I describe findings regarding both the direct and indirect links that have been the most telling in establishing the connection between our gut and our mental health. An example of this is the growing recognition of the connection between inflammation within the digestive tract (as caused by the gut microbiome) and depression (Bercik, Collins, & Verdu, 2012, p. 407). A comparable and even more widespread example of this gut-mental health connection is also the somatic response many people feel when anxious, which even has a colloquial label: “butterflies in my stomach.” More specifically, in this [portion of the] thesis, I will focus on the link between our microbiome and three of the most common psychiatric disorders—schizophrenia, depression, and anxiety.
The composition of our microbiota is directly linked to our ancestry, largely through the types of foods and environments to which our ancestors have had access. The data and access to empirical content (i.e. research reports, experiments) regarding this information was most readily available in more privileged countries (i.e., with more resources and people to collect mass data, especially ones concerning mental health), such as the United States and parts of Europe. Class, culture, and race are also factors that influence the gut microbiome and its connection to and/or implications on mental illnesses, but there are no studies found, even within these privileged countries, that focused specifically on such influences. There are very few studies that focus simply on the influence of these individual factors on just the gut microbiome itself.
I have written this thesis for readers who may not be overly familiar with the language of STEM, because I think this thesis is applicable to anyone with interest and care in their diet and mental wellbeing. I have, hence, also explored ways that I can make my thesis more accessible, such as through more creative and artistic mediums, and have created a short comic—presented toward the end of this report—to depict the known relationship of the gut microbiome to the brain and mental health in general.
A Brief Introduction to the Gut Microbiota
Though the study of the human gut microbiota is still new and increasingly expanding, the microbial community within us is far from new. They have been with us since the beginning of our evolution (a reminder: microbes pre-exist us), and the influence has always been mutual. There is a term for our alliance — “an animal holobiont” — which is a very modern term (most studies that use this term have only been published in the last five years) for such an old concept (Dominguez-Bello, Godoy-Vitorino, Knight, & Blaser, 2019, p. 1108). Some of the bacteria within our microbiome, namely Bacteroidaceae and Bifidobacteriaceae, have been traced back “to a common primate ancestor >15 million years ago” (Moeller et al., 2016, p. 380). We have co-evolved with these microbial communities; they have influenced us for biological and social reasons alike, such as “dietary changes [i.e. based on geography and climate] and exposures to famine” repeatedly over the course of history, that have led to “major [microbial] selective pressures,” though these specific pressures and influences are not yet known (Dominguez-Bello et al., 2019, p. 1108). They, however, may be key in understanding our body and mind’s interaction with the modern world, especially one that is actively globalizing and urbanizing.
It is generally agreed that we are sterile in the womb (however, since this is still a new field, few studies have been conducted to contradict this finding). Studies have shown that we get most of our microbes during the birthing process, specifically through the birth canal during vaginal birth, which is not the most common method of birth in many countries. The extent to which C-section, as well as antibiotic treatments given pre- and postnatally, could be facilitating intergeneration loss of microbial communities isn’t known yet. The general understanding within the field is still in its beginning stages; there have been “hypotheses about [the] roles of the microbiota in mother-baby bonding”, “[emerging research about] ethnic differences in vaginal microbiota,” and the possibilities of the residual antibiotics, which are given to “>50% of pregnant women ... during pregnancy,” being a “selective force [for the infant’s initial colonizing organisms]” but unfortunately, none of which has solid findings yet (Blaser & Dominguez-Bello, 2016, p. 559-560). Additionally, most of the results and perspectives of these studies focus on the possible physical connections, i.e. the probabilities of immune diseases developing in relation to the mentioned factors, hence we do not yet know the implications these factors could have on the link with our mental health.
Information on general postnatal development, i.e. diet, age, and environment, of the gut microbial community is also limited. It is also not yet known how industrialization and urbanization may be affecting our gut microbiota, though there has been research showing that there is a substantial loss of bacterial diversity as a result, as well as a correlating rise of “immune and metabolic diseases” in the last few decades, such as asthma and IBD (Dominguez-Bello et al., 2019, p. 1110). Urbanization has also been associated with sanitation and vaccines, now more than ever, neither of which has been extensively studied under the lens of gut microbes as of yet.
Despite our limited understanding of the relationship between the modern world and our gut bacteria, they have generally, and perhaps intrinsically, always been established as very important to us in a very physical sense. An example is our inability to process milk. Lactose intolerance is not experienced by everyone, especially not in infants, who solely depend upon their mother’s milk (or formula). Infants are able to do so because of the microbes they obtain during labor, such as lactic acid bacteria and others that process “indigestible milk glycans known as human milk oligosaccharides (HMOs)” (Dominguez-Bello, et al., 2019, p. 1109). This is proof of the aforementioned co-evolution – that something as vital as milk is biologically indigestible to us without these microbes. I have written this thesis with the same hope of establishing the gut microbiome as an important factor, especially in our mental and subsequent behavioral health.
Schizophrenia
Is there a relationship between schizophrenia and the gut (microbiota)? No - at least so far, there haven’t been any concrete findings of such. However, some studies have found associations between schizophrenia and the gut microbiota, although the mechanism is still unclear.
One study by Rodrigues-Amorima et al. (2018) suggests, using an epigenetic framework, a strong linkage between digestive diseases and mental illnesses, as people with “microbiota dysbiosis” (an imbalance of microbes, which is often a reduction in the diversity of microbes) also tend to have illnesses of either kind (either digestive or mental illness in general). It also suggests that people with digestive diseases tend to also have mental illnesses. These researchers found that the gut microbiota’s interaction with the nervous system has largely been “via the vagus nerve, the metabolism of tryptophan, enteroendocrine signaling, and the production of short-chain fatty acids that inhibit the deacetylation of histones” (p. 3).
The same researchers (Rodrigues-Amorima et al., 2018) also suggested that gut microbiota can trigger the production of immune mediators, which are important for homeostasis (and immunity). This, they suggest, is also the crucial link between the gut microbiota and schizophrenia – the gut microbiota allows for immune mediators to cross the blood-brain barrier, which then bind to receptors in the microglia and change their function (removing damaged/infected neurons). The immune mediators most often mentioned are cytokines involved in the immune response to gluten, and when paired with microbial dysbiosis, “is positively correlated with the symptomatology and severity of schizophrenia” (p. 5), as these cytokines are also involved with afferent nerve receptors. This is why many individuals with gluten sensitivity/coeliac disease often also have schizophrenia. This is a major contributor, along with suicide attempts, to the shortened lifespan (15 years shorter) of many schizophrenia patients.
Rodrigues-Amorima and colleagues further note that disruption to the gut barrier also results in disruption to the intestinal permeability, which can lead to not just microbiota dysbiosis, but also diseases and viruses entering the body. This also results in several diseases being linked to schizophrenia, as this disruption also affects the neurological processes. Additionally, gut bacteria can also produce neurotransmitters to directly affect brain activity, “such as GABA, noradrenaline, dopamine, serotonin, epinephrine, acetylcholine, histamine and potential bioactive neuropeptides” (5). It can also affect such activities, especially of GABA (important for reducing neuronal excitability, i.e. relieving anxiety), by changing certain GABA receptors, changing the areas of the brain (i.e. cortical regions over hippocampus) GABA is expressed more in, and affecting the vagus nerve in its regulation of GABA. The vagus nerve is especially important for the communication between the CNS and the enteric nervous system (the gut microbiota).
Finally, tryptophan, an amino acid obtainable only by diet, is essential for producing serotonin in the CNS after being absorbed and obtained by the gut bacteria. The gut bacteria work closely with liver enzymes to metabolize the amino acid, and the inactivity of the latter often results in decreased levels of tryptophan, which is the case found in patients with inflammatory bowel diseases. Similarly, the pathway that the same enzymes are found in is also linked to schizophrenia.
The diagram, below, from the Rodrigues-Amorima et al. (2018) article displays the great complexity of this possible connection. Important to notice in Figure 1, below, is that all these connections drawn within the diagram are, as far as the study can deduce, possible as a result of the vagus nerve. It is established as the main connection between the brain and the gut microbiota.
Moreover, in a recent review of the literature (six separate studies), Szeligowski, Yun, Lennox and Burnet (2020) reported that the bacterial class Clostridia, along with the bacterial phylum Proteobacteria and Firmicutes, is connected to schizophrenia. They further propose that this class has been identified as “enriched in schizophrenia”– though only in one study out of six. The remaining five studies found cases of both reduced and increased levels of the relevant bacteria. The authors list multiple reasons for such inconsistencies, such as small sample sizes that did not allow for statistical significance to be reached or recording and observing at the phylum or class taxon (see Figure 2), which disregards the functions of individual species of bacteria (which are highly likely to be different), as well as possible environmental factors on the microbiota, such as smoking, comorbid metabolic and cardiovascular illnesses (i.e. obesity, diabetes, hypertension) and usage of antipsychotics.
Figure 1. The Gut Microbiota-Brain Route, including: Immune system, enterendocrine cells, vagus nerve, tryptophan metabolism, neurotransmitters, hormonal communication, etc.
Rodrigues-Amorima et al. (2018)
In the following figure (Figure 2), I have created a taxonomic chart, which is used by scientists to categorize every organism. The most fundamental and general grouping begins at the top, ending with the most specific grouping at the bottom. There are two examples provided: Homo sapiens (humans) and Lactobacillus acidophilus, a type of bacteria found in the human intestines.
Figure 2. Taxonomic chart, with two examples: Homo sapiens (humans) and Lactobacillus acidophilus (a species of bacteria found in the human gut).
Domain | Eukarya | Bacteria |
Kingdom | Animalia | Bacteria |
Phylum | Chordata | Firmicutes |
Class | Mammalia | Bacilli |
Order | Primata | Lactobacillales |
Family | Hominidae | Lactobacillaceae |
Genus | Homo | Lactobacillus |
Species | Homo sapiens | Lactobacillus acidophilus |
Made by author
To support their conclusion that antipsychotics (the treatment for schizophrenia)--and not the illness itself--may be the cause of microbial inconsistencies, Szeligowski et al. (2020) cite a study done on rats, in which olanzapine (a common drug treatment for schizophrenia) was used and resulted in the increase of the bacteria Firmicutes and decrease in Bacteroidetes. The only bacteria, these authors note, that has been consistently found to be increased in individuals with schizophrenia is Lactobacilli, which is perplexing, they suggest, as it is found within probiotics, which are meant to benefit mental health.
Finally, these authors also referenced a study done with fecal transplantation from schizophrenia patients to germ-free (GF) mice, which resulted--in the mice--in hyperactivity, behavioral despair, and exaggerated startle responses, which mimics behaviors seen in schizophrenia. These findings are, the authors point out, still not confirmation of any link between the gut microbiota and schizophrenia, especially since these same mice also did not change their performance levels in other cognitive-behavioral areas (e.g., the Y-maze, sociability tests, and pre-pulse inhibition tests).
The complexity of the findings of these studies and the mixed conclusions all suggest that the focus of many studies currently are limited in that they only are looking from a very general angle and hoping to discover general trends. This also shows that this is a field still at its beginning stages, as it seems that there is still very little mapping of specific bacterial species within the gut and very little differentiating of their specific functions. This may be because the current technology does not allow for such discoveries yet, or because the field is not receiving enough funding and attention for them to use such technologies.
Depression
The current findings on depression continue the trend of a vague relationship between the mental illness and the gut microbiome, but many studies have looked more specifically and thoroughly into the bi-directionality of the gut-brain axis than was seen in schizophrenia, and believe that the hypothalamic-pituitary-adrenal (HPA) axis is especially relevant to the relationship.
Dinan and Cryan’s (2013) article looks at the importance of the gut-brain axis through the review of multiple studies, and the first evidence for its importance is observed via the HPA axis, as its function is to regulate the gut-brain axis. The HPA is often observed to have numerous changes in depressed patients, such as increasing all of the following: cortisol levels (stress hormones), CRF levels (stimulates anxiety and decreases appetite), and pro-inflammatory cytokines (immune responses). Furthermore, there have been studies showing that microbes directly influence the HPA; a study performed by Sudo et al. showed the possible extent of influence: “[the] hyper-response of the HPA [such as the changes listed previously, can be] reversed by monoassociation [which is the colonization of a single species on a germ-free organism] with a single organism, Bifidobacterium infantis” (p. 715).
The following Figure 3, from Dinan and Cryan, describes the bidirectional connection between the gut-brain axis, as deemed relevant to depression. According to Dinan and Cryan, the diagram represents how different parts of the gut-brain axis (such as the vagus nerve, which transfers signals from both the gut to the HPA axis, and vice versa) interact as a result of chronic stress and depression. The immune system is also involved.
Figure 3. Gut-Brain Axis & Depression
Dinan and Cryan’s (2013)
Dinan and Cryan continue their analysis of the HPA axis’ relevance with a review of Park and colleagues’ study (Park et al., 2013), which involved the olfactory bulbectomy (having olfactory bulbs, which are nerve cells relevant to smell, removed) performed on mice. The bulbectomy was performed because the bulbectomized mice had changes in the gut microbiota parallel to mice “with a depression-related behavioral and endocrine phenotype,” though it is uncertain why this similarity is produced (Dinan & Cryan, 2013, p. 715).
The bulbectomized mice were more likely to act with “prolonged immobility or behavioral despair” (Dinan & Cryan, 2013, p. 715) in tests than the control mice (those without a bulbectomy), and were recorded to have an over-heightened (by two-fold) activation of the HPA axis via the basal expression (which is related to the expression of voluntary behavior) in comparison to the control mice. This suggests an indirect link between the gut microbiota and the expression of voluntary behavior, which could be further explored to understand how possible hindrances of voluntary behavior (common in depression) are influenced by the gut microbiota.
The replication of a depression model via a bulbectomy to stimulate a similar change in the gut microbiota also suggests more connections that are yet to be explored, such as the connection to smell and related nerve cells with the gut microbiome. However, it should be noted that a bulbectomy may not be a valid model of depression, even if similar results were produced, as other studies argue that it is a model of neurodegeneration instead.
Overall, Dinan and Cryan argue that there is a promising relationship between the gut microbiota and depression, especially one facilitated by the HPA axis. However, the same lack of understanding is echoed. The specific mechanisms of how the HPA axis interacts with the gut organisms are still unclear, as many current studies are still focused on proving that there are interactions.
However, there are studies that have begun to narrow down the types of bacteria that are interacting with the specific types of hormones and neurotransmitters in our brains to result in depression. Naseribafrouei and colleagues’ (Naseribafrouei, Hestad, Avershina, Sekelja, Linløkken, Wilson, & Rudi, 2014) study examined and compared fecal samples from 37 depressed and 18 non-depressed people via “deep Illumina sequencing of 16S rRNA gene amplicons.” The basis of their study was based on other studies that have shown indirect connections between depression and the microbiota, such as the production of GABA by the microbiota and the level of serotonergic (serotonin) signaling.
However, Naseribafrouei and colleagues found no statistically significant correlation regarding bacterial species richness (note that ‘species’ is used, but the taxonomic order examined is still at phylum); the most pronounced correlation was the “general underrepresentation of Bacteroidetes [in relation to] depression” (p. 1158), which is also correlated with obesity, but none of the patients were obese. It also seemed that medication (for depressed patients) did not affect the results, though it was not stated the extent of medication that was used (i.e. for how long, which types). On the other hand, Alistipes (genus) was found to be the most elevated in the depressed group compared to the non-depressed control group, which is also a bacterial genus found in chronic fatigue and IBS, as well as previous associations with inflammation.
There was also a bacterial genus, Ocillibacter, that was found to be producing valeric acid, which is capable of binding to the GABA receptor, decreasing the ability for GABA to bind, which would result in heightened anxiety and stress. Both bacterial genera can be promoted via diet, especially one high in sugar and “with a low healthy food diversity” (Naseribafrouei et. al, 2014, p. 1160), which also suggests that treatment for depression could even begin with food.
Much of the differences recorded in the studies are based on the proportion of bacterial phyla, which has not indicated a substantive change or yielded significant results, suggesting that the phylum level of examination is still too vague. There was, however, a general consensus for the reduced diversity of microbiota and its possible relevance to depression.
Anxiety
Anxiety has always been closely tied to the gut, as seen by common colloquial phrases ranging from “I’ve got butterflies in my stomach” to “I’m so nervous I think I’m going to throw up”. Although it is not the only emotion that can trigger changes in the gut, it is the most commonly recognized. Hence, it is no surprise that it offers the most information about this growing field.
One article by Neufeld, Kang, Bienenstock, & Foster (2010), mentions a study by Sudo et al. (2004), where the idea of time as a factor within the relationship between the gut microbiome and anxiety (“stress systems” within the CNS) is first introduced. There seems to be a critical window in which the gut microbiota can be introduced and result in an effect on mice – the GF mice in Sudo’s et al.’s study experienced “[the reversal of] the locomotor and anxiety-like behavior” within the experiment only when “[the gut colonization] of GF mice with SPF flora [occurred] at 6 weeks (young adult) but not at 14 weeks (adult).” This is a factor that no other studies, up until this point of the thesis, had mentioned, and could possibly partially account for the vague results that these studies have also found themselves with.
Sudo et. al’s findings are likely because most studies mentioned had worked with humans (i.e. examining fecal samples), and time is a factor completely out of their influence. The reason for the time limit that is imposed on the effect of the gut microbiome’s interaction with the brain is proposed by Neufeld: “There is a critical period postnatally in which [the] HPA axis dysfunction and behavioral traits become relatively hard-wired into adulthood,” as well as how neural pathways become more dominant with time and usage, and hence the introduction of new gut microbes at a later time will have a lesser effect.
The importance of time may also extend to why the majority of human gut flora is acquired from birth (via the birth canal), and is established by the age of five years. Rodriguez, Murphy et al.’s (2018) study argues that “once established, the composition of the gut microbiota is relatively stable throughout adult life,” though it is still susceptible to changes, especially when the body experiences sickness/an abrasive introduction of other gut microbes, such as from immense stress. Another study, to be mentioned next, by Crumeyrolle-Arias et. al (2014) also mentions the “gut microbiota composition and metabolism of autistic children are different from those of the general population,” suggesting a further connection between the gut microbiota and neurodevelopmental disorders. This could also be further connected to the influence of time on the connection between the two, as it is a neurodevelopmental disorder. The introduction of this factor brings to light the possibility of many other factors that are likely crucial, but difficult to control within studies, that are not accounted for.
Neufeld et al. ’s study is not exempt from contrasting results with other similar studies. Their study placed mice in an elevated plus maze (EPM), and the germ-free (GF) mice were recorded to have less anxiety-like behavior than specific pathogen-free (SPF) mice, as they tended to stay in “the open arms of the EPM”. Another study, by Crumeyrolle-Arias et al. (2014), found that the GF mice reacted with more stress.
This latter study also compared GF and SPF mice, and specifically, their biological reaction to stressful situations as opposed to behavioral reactions. There was an initial test to evaluate the base stress reactions of the mice by having them interact with another unknown mouse in an unfamiliar environment. The set situation used to collect data was by putting the mice in an open-field (hence the name of the open-field (OF) test) and shining a strong light on the center. The GF mice reacted more stressfully to the situation. This is the expected result, as the gut microbiota is hypothesized to counter stress, and the GF mice, which are bred without exposure to microorganisms, would not have this ability to counter stress. The biological response to the situation was recorded as “a hypersecretion of adrenocorticotropic hormone (ACTH) and corticosterone (CORT)” in both types of mice, but the SPF mice had lower levels of both because it “was partly corrected by gut microbiota reconstitution with fecal bacteria of the SPF mice.”
These stress hormones are released as a response to “an acute restraint stress” (an uncontrollable stress situation), and “by the increase in CRF (corticotropin-releasing factor) gene expression in the hypothalamus and the decrease in GR (glucocorticoid receptor) gene expression in the hippocampus,” which suggests that the gut microbiota is able to extend its influences to counteract effects the hypothalamus and hippocampus, or possibly even directly affect these regions, as seen by the response of the SPF mice. It should be noted that the results of this study noted the GF mice did not have any difference in their sensorimotor functions, but there was a difference in their social investigation – the GF mice sniffed their environments less and were more anxious. It is assumed that their fear/stress greatly outweighed their curiosity, but it could also suggest that they were simply less curious.
The third (and final) literature review to be mentioned is by Simpson, Mu, Haslam, Schwartz and Simmons (2020), which focuses on the common comorbidities of anxiety. The co-occurrence of anxiety and depression is very well known, as over “81% of individuals with a current anxiety disorder report a lifetime history of depression.” However the reason for the co-occurrence is still unknown, and the literature review by Simpson et al. argues that the explanation may lie in another, and lesser-known, co-occurrence: irritable bowel syndrome (IBS).
It has been estimated that the co-occurrence of IBS and anxiety and depression is “between 44 and 84%.” This co-morbidity is also seen in rodents, which were the subjects in the non-human studies Simpson et al’s review looked at. The co-morbidity was simulated via early life maternal separation (MS) in two of the studies, which was used as a model of anxiety and depression and resulted in IBS-like symptoms in adulthood. Other studies used olfactory bulbectomy (OBx), fecal microbiota transplant (FMT, from human participants with or without depression), antibiotic treatment, and strain comparisons, which are the general methods used across the studies mentioned in previous chapters. The human studies relied on cohort comparisons and cross-sectional studies.
The results found that gut dysbiosis was absolutely crucial on two fronts. Firstly, gut dysbiosis leads to increased communication with stress systems via the vagus nerve, which can lead to anxiety and or depression, as “elevated cortisol levels and inflammatory markers have been implicated in anxiety and depressive disorders'' in the brain, which leads to hypercortisolemia (increased levels of cortisol) via the HPA axis, which cycles back to gut dysbiosis. Secondly, gut dysbiosis leads to increased intestinal permeability, which leads to IBS. I have created a diagram (Figure 4, below) that shows the feedback loop that is created, which links IBS to anxiety and depression.
The diagram below visualizes the cycle that explains the link between IBS and anxiety. Important to note in this diagram is the role of gut dysbiosis, which shows how increased stress levels (i.e. anxiety) can lead to IBS.
Figure 4. The cycle of gut dysbiosis and its link to anxiety is represented, as well as its relevance to IBS.
Made by author
This cyclical relationship between the gut microbes and the brain (especially the stress systems) is furthered by the gut microbiota compositions found in the participants within Pittayanon, Lau, Yuan, Leontiadis, Tse, Surette, & Moayyedi’s (2019) study that have IBS. The stress systems change the intestinal environment by “[increasing] gastrointestinal motility and inflammation [which] provide favorable conditions for bacteria…” that are found in higher abundance within the mentioned participants, such as Lactobacillus and Bacteroides species. This creates an even stronger cycle, as the intestinal environment would be more primed for gut dysbiosis. There was further discovery that the mentioned bacteria secreted exotoxins that, “may induce inflammation that is subsequently communicated to the brain,” which further facilitates the previously mentioned favorable condition. This is further supported by the “lower bacterial alpha diversity”, suggesting that the bacteria that currently thrive in the environment are likely to only continue securing their ideal conditions of the gut environment.
However, it should be noted that one of the studies analyzed within the review only looks at participants with IBS, so it cannot be assumed that their findings apply to the comorbidity. In fact, “most studies [compare] the gut microbiota of each condition separately.” It should also be noted that there have been “studies [that] broadly suggest participants with co-morbid IBS and anxiety/depression have a unique gut microbial profile compared to participants with IBS-only,” suggesting that PIttayanon et al.’s (2019) results may not connect much to anxiety/depression, but again, that connection has still been barely explored by the field. There are still many possibilities for their connection, which Simpson et al. suggests can only be understood when studying both IBS and anxiety/depression comorbidity due to the possibility of “distinct microbial associations, and that unmeasured comorbidity obscures microbial correlates unique to one condition.”
There are also many more difficulties in studying this connection. The change in the standards, i.e. from Rome III to Rome IV (changing the diagnosis of IBS from three times a month to once a week) excludes 15-50% of the previously diagnosed cases. Simpson et al. also critiques that “most studies failed to describe the method of sequence generation, allocation concealment, or baseline characteristics of animals.” In addition, not only is there a lack of specificity in comparing and analyzing bacteria, which is a big critique first introduced in the chapter looking at schizophrenia, but there is very little research looking at archaea, viruses, fungi, and other eukaryotes that comprise the gut microbiota. Within human studies/samples, there is also usually little to no mention of diet, much less control of such, such as the use of antidepressants, probiotics, laxatives, etc., which could greatly contribute and affect the results received and analyzed by the studies.
Creatively Communicating the Brain-Biome Connection
This thesis was intended to generally make the current gut-brain research more accessible to the general public. I have illustrated a mini 8-panel comic to achieve this goal—to make the thesis more generally relatable to the reader. The comic focuses on the findings within Depression and Anxiety and follows briefly a character who struggles with both mood disorders as well as IBS and introduces the connection between the two. The illustrations also introduce the current field, establishing what is known based on the analysis within this thesis. Finally, I hope that this visual presentation of information leaves the reader with possibilities within this field for a greater understanding of the gut-brain relationship, especially with the novelty of so many of the ideas within it.
Conclusion
It is quite clear, across the neuro-disorders explored within this thesis, that while there are bi-directional links connecting many psychological disorders (e.g. depression, schizophrenia, and anxiety) to the gut microbiota, these links, currently, have generally only been explored indirectly. They have often been explored via comorbid digestive or immune disorders, such as IBS and coeliac disease. The connections between the co-morbidities and the gut microbiota are better established but are yet to be fully explained, as well. The current working explanation for this gut-brain connection is based primarily around gut dysbiosis, a general term for the imbalance of microbes; and the hypothesis is that this imbalance often leads to a cascade of events not only within the body but also within the mind.
As this thesis summarizes, many psychological disorders may also be understood by the pathways between the brain and the gut, especially the vagus nerve and the immune system. This includes hormones and neurotransmitters—i.e. some of which are produced in the gut and then released into the HPA axis through the vagus nerve. The immune system is also involved via its protective responses, and the neuro-disorders are often a result of such responses having gone awry. Dinan and Cryan’s (2013) Gut-Brain Axis & Depression diagram, referenced in Chapter 3 (and presented again below), briefly outlines the described relationship between the gut microbiome and the brain.
Dinan and Cryan’s (2013)
This thesis itself, however, discusses very little of the gut microbiome itself in detail, such as the bacterial composition of the gut microbiome and how it differs across psychological and neurological disorders, as well as within individuals without these disorders. In the literature, I found that there was often mention of the bacterial families and phylum that differed in composition, but there was very little paired information about these bacteria.
Understanding the difference in composition, and particularly the function of the bacteria mentioned, to whatever extent it has been studied, would have greatly aided this analysis. It could have helped to better explain gut dysbiosis (such as the specifics of its process), as well as perhaps better explain how it occurs in the first place. Future research building on the analysis presented here may focus more on the gut-biome itself and these specific connections to psychological and neurological disorders.
This limitation, however, is also reflective of the field, as well. There is very little known about the gut microbiome, despite it “[inhabiting] 1013–1014 micro-organisms” (Dinan & Cryan, 2012, p. 1369). The majority of the focus within studies is on bacteria, though the microbiome is also made up of other domains: archaea, fungi, and viruses. What is known about the bacteria is still limited in scope as well, especially analyzed in Chapter 2 (Schizophrenia). Therefore, even with a deeper dive into the individual bacterial phylum and their functions, it would still not have painted a whole picture of what gut dysbiosis is. The thesis does establish the importance of gut dysbiosis in the link between the brain and the gut, and that is arguably the most accurate representation of the current standing of the field.
The general findings of this thesis are that the gut-brain connection is much more intricate than commonly realized. We may come to recognize that the gut microbiota is a stronger contributor to the biological basis of behavior and mental health—and hopefully, this will occur with further development of this field. However, as seen from the thesis, it can begin to explain the co-morbidity of many disorders, as well as the symptoms within the neuro-disorders themselves. The gut microbiome may directly influence behavior more than we now know, it holds importance within our health, and its interaction with the modernizing environment deserves to be further understood.
I also observed that the research in this field is, as of yet, generally atheoretical. There is no driving, overarching theory regarding the gut-brain connection that research could use to support, guide, advance, or even challenge current findings. Rather, the research is still explorative, and results, even regarding the gut microbiome itself, are still tentative. But, I also believe this is what makes this field so worthy of greater attention and research.
References
Bercik, P., Collins, S. M., & Verdu, E. F. (2012). Microbes and the gut-brain axis. Neurogastroenterology & Motility, 24(5), 405–413. https://doi.org/10.1111/j.1365-2982.2012.01906.x
Blaser, M. J., & Dominguez-Bello, M. G. (2016). The Human Microbiome before Birth. Cell Host & Microbe, 20(5), 558–560. doi:10.1016/j.chom.2016.10.014
Chen, G., Xu, T., Yan, Y., Zhou, Y., Jiang, Y., Melcher, K., & Xu, H. E. (2017). Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacologica Sinica, 38(9), 1205–1235. doi:10.1038/aps.2017.28
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This is an excerpt from my senior thesis, published in 2022.
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