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Journal ArticleDOI

The microbiome, immunity, and schizophrenia and bipolar disorder

01 May 2017-Brain Behavior and Immunity (Brain Behav Immun)-Vol. 62, pp 46-52
TL;DR: The ultimate test of the role of the microbiome and immune-mediated pathology in schizophrenia and bipolar disorder will come from clinical trials of therapeutic agents which alter gut microbiota or gastrointestinal inflammation.
Abstract: Schizophrenia and bipolar disorder are serious neuropsychiatric disorders of uncertain etiology. Recent studies indicate that immune activation may contribute to the etiopathogenesis of these disorders. Numerous studies in animal models indicate that the mucosal microbiome may influence cognition and behavior by altering the functioning of the immune system. It is thus likely that the microbiome plays a role in human psychiatric disorders. The study of immune alterations and the microbiome in schizophrenia and bipolar disorder is in its infancy. Two recent investigations of the oro-pharyngeal microbiota in schizophrenia found differences between cases and controls. Other studies have found increased gastrointestinal inflammation in schizophrenia and bipolar disorder based on measures of microbial translocation. Several studies have also found an association between the receipt of antibiotics and an increased incidence of psychiatric disorders, perhaps due to alterations in the microbiome. Studies to characterize the intestinal microbiome of individuals with these disorders are in progress. The ultimate test of the role of the microbiome and immune-mediated pathology in schizophrenia and bipolar disorder will come from clinical trials of therapeutic agents which alter gut microbiota or gastrointestinal inflammation. The successful development of such modalities would represent a novel strategy to prevent and treat serious psychiatric disorders.

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The microbiome, immunity, and schizophrenia and bipolar
disorder
Faith Dickerson
1,*
, Emily Severance
2
, and Robert Yolken
3
1
Sheppard Pratt Health System, Baltimore, MD USA
2,3
Johns Hopkins School of Medicine, Baltimore, MD USA
Abstract
Schizophrenia and bipolar disorder are serious neuropsychiatric disorders of uncertain etiology.
Recent studies indicate that immune activation may contribute to the etiopathogenesis of these
disorders. Numerous studies in animal models indicate that the mucosal microbiome may
influence cognition and behavior by altering the functioning of the immune system. It is thus
likely that the microbiome plays a role in human psychiatric disorders. The study of immune
alterations and the microbiome in schizophrenia and bipolar disorder is in its infancy. Two recent
investigations of the oro-pharyngeal microbiota in schizophrenia found differences between cases
and controls. Other studies have found increased gastrointestinal inflammation in schizophrenia
and bipolar disorder based on measures of microbial translocation. Several studies have also found
an association between the receipt of antibiotics and an increased incidence of psychiatric
disorders, perhaps due to alterations in the microbiome. Studies to characterize the intestinal
microbiome of individuals with these disorders are in progress. The ultimate test of the role of the
microbiome and immune-mediated pathology in schizophrenia and bipolar disorder will come
from clinical trials of therapeutic agents which alter gut microbiota or gastrointestinal
inflammation. The successful development of such modalities would represent a novel strategy to
prevent and treat serious psychiatric disorders.
Keywords
immunity; microbiome; schizophrenia; bipolar disorder; gastrointestinal; antibiotics; probiotics
1. Introduction
Schizophrenia is a neuropsychiatric disorder with an onset typically in adolescence or young
adulthood and a course which usually persists throughout the lifespan. Characteristic
symptoms include hallucinations and delusions as well as apathy and social withdrawal;
many affected individuals also have reduced cognitive abilities and impaired social
*
Corresponding Author: Stanley Research Program, Sheppard Pratt Health System, 6501 North Charles St, Baltimore, MD USA
21204; fdickerson@sheppardpratt.org; Phone 410-938-4359, Fax 410-938-4364.
2
Johns Hopkins School of Medicine, Stanley Laboratory of Neurovirology, Department of Pediatrics, 600 N. Wolfe St., Baltimore,
MD USA 21287; Esevera1@jhmi.edu
3
Johns Hopkins School of Medicine, Stanley Laboratory of Neurovirology, Department of Pediatrics, 600 N. Wolfe St., Baltimore,
MD USA 21287; rhyolken@gmail.com
HHS Public Access
Author manuscript
Brain Behav Immun
. Author manuscript; available in PMC 2017 July 10.
Published in final edited form as:
Brain Behav Immun
. 2017 May ; 62: 46–52. doi:10.1016/j.bbi.2016.12.010.
Author Manuscript Author Manuscript Author Manuscript Author Manuscript

functioning. Because the disorder disrupts multiple life domains and typically persists for
decades, the global burden of disease is high (Whiteford, Ferrari, Degenhardt, Feigin, & Vos,
2015). Bipolar disorder is another serious mental illness and shares many features with
schizophrenia including some of the characteristic symptoms and the lifelong course.
(Dacquino, De Rossi, & Spalletta, 2015; Jobe & Harrow, 2005). Both disorders are
categorized by their phenotypic features rather than any biological markers and their
etiology is not fully understood. Genome-wide association studies show a great deal of
genetic overlap between schizophrenia and bipolar disorder (Lichtenstein et al., 2009; Van
Snellenberg & de Candia, 2009) However, while genetic factors are involved in both
disorders, risk genes which have been identified account for a small portion of disease risk.
For example, a recent genome wide study in schizophrenia found 108 independent loci that
account for approximately 7% of the risk of developing schizophrenia from polygenic
scores, (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014) Of
note, many of the genetic loci that were identified are known to modulate inflammation and
the immune response.
Previous studies have demonstrated that both schizophrenia and bipolar disorder are
associated with alterations of the systemic immune system including low-grade chronic
inflammation (increased plasma cytokines, soluble cytokine receptors, chemokines, acute
phase reactants) and T-cell activation features; these findings are delineated in previously-
published review articles(Anderson & Maes, 2015).(Rosenblat, Cha, Mansur, & McIntyre,
2014) (Leboyer et al., 2016). The immune system provides a two way communication
pathway between the gut and the brain via the vagus nerve, short chain fatty acids, and a
number of soluble mediators(Erny, de Angelis, & Prinz, 2016; Hyland & Cryan, 2016;
Levite, 2016; Sherwin, Sandhu, Dinan, & Cryan, 2016). It has been established that the gut
microbiota can influence brain function and thus may play a role in diseases such as
schizophrenia and bipolar disorder which are traditionally seen as brain-based (Fond et al.,
2015).
The study of the microbiome is relatively new and most of the investigations to date have
taken place in animal models. Multiple studies have documented an interaction between the
gut microbiome, immunity, cognitive functioning and behavior in a number of models, most
of which involve rodents (Desbonnet et al., 2015). Studies linking these findings to human
psychiatric disorders are more limited.
2. Scope of review
The purpose of this article is to summarize what is known about immune alterations and the
microbiome based on human studies in schizophrenia and bipolar disorder. This field of
inquiry is still in its infancy and the number of studies to date is small. However, the
groundwork is being laid to better understand immune abnormalities which contribute to the
etiology of these major psychiatric disorders and to identify how knowledge of the
microbiome might result in novel methods for the treatment of these disorders.
Dickerson et al.
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Brain Behav Immun
. Author manuscript; available in PMC 2017 July 10.
Author Manuscript Author Manuscript Author Manuscript Author Manuscript

3. Results
Research about immune alterations and the microbiome in schizophrenia and bipolar
disorder falls into several categories as described below.
3.1. Studies of the oropharyngeal microbiota in schizophrenia
There have been numerous studies of the fecal microbiome in otherwise healthy children
and adults (Collado, Rautava, Isolauri, & Salminen, 2015; Lozupone, Stombaugh, Gordon,
Jansson, & Knight, 2012). However the collection and prompt processing of fecal samples
from individuals with severe psychiatric disorders is problematic. Published studies
analyzing the fecal microbiome of individuals with schizophrenia are currently lacking. The
oropharyngeal microbiome can be assessed from throat swab samples which are more easily
accessed than samples from the gastrointestinal tract and thus allow potentially for larger
sample sizes. Furthermore, while there are many differences in the microbial composition of
the fecal and oral microbiome, some studies have documented overlapping metabolic
pathways in the different sites (Segata et al., 2012). For this reason many of the studies in
our population have focused on the oral microbiome. Furthermore, we have relied on
metagenomic sequencing rather than the commonly used 16S sequencing since studies have
documented a role for viruses (Houenou et al., 2014), fungi(Severance et al, 2016) and
protozoa (Torrey, Bartko, & Yolken, 2012) in the pathogenesis of the psychiatric disorders.
A meta-genomic analysis of the oropharyngeal microbiome in 16 adults with schizophrenia
and 16 non-psychiatric controls found differences at both the phylum and the genus levels.
(Castro-Nallar et al., 2015) At the phylum level, schizophrenia samples exhibited higher
proportions of Firmicutes across samples in comparison to controls; in the controls a higher
relative proportion of Badteroidetes and Actinobacteria was observed. Regarding species
diversity, controls were richer in the number of species compared to schizophrenia samples
but less even in their distribution (Figure 1).
Out of a total of 25 differentially abundant species (bacteria and fungi), 6 microbial species
were more abundant in cases than controls after adjusting for relevant covariates. Lactic acid
bacteria were relatively more abundant in schizophrenia including Lactobacillus and
Bifidobacterium with the largest effect found in Lactobacillus gasseri which appeared to be
at least 400 times more abundant in schizophrenia patients than in controls. The study also
found that 18 metabolic pathways that were enriched and 14 decreased in schizophrenia
relative to controls. Pathways that were significantly altered in schizophrenia were related to
environmental information processes such as saccharide, polio, and lipid transport systems
(Figure 2).
Another study of the oropharyngeal microbiome focused on bacteriophages, viruses that
infect bacteria and alter their metabolism and replication, in samples from 41 adults with
schizophrenia and 33 non-psychiatric controls.(R. H. Yolken et al., 2015) Of the 79 distinct
bacteriophage samples that were identified, one, Lactobacillus phage phiadh, was
significantly more abundant in schizophrenia cases than in controls after adjustment for
multiple comparisons and demographic covariates (Figure 3). Interestingly the group
Dickerson et al.
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differences were larger for the phage than for its host bacteria underscoring the importance
of examining viral sequences in studies of the microbiome relating to psychiatric disorders.
Within the schizophrenia group, the level of this phage was significantly associated with the
presence of immunological disorders such as diabetes, which are common co-morbid
conditions in individuals with schizophrenia (Schoepf, Uppal, Potluri, & Heun, 2014). The
level of Lactobacillus phage phiadh was also relatively increased in individuals who were
being treated with therapeutic valproate, a medication commonly used for the adjunctive
treatment of schizophrenia (Tseng et al., 2016). This finding is of interest since valproate has
been shown to modify the microbiome in mouse models of autism in the context of in utero
exposure, probably related to us homology with short chain fatty acids(de Theije et al.,
2014)). This finding is of note since the mechanisms by which valproate improves the
symptoms in some individuals with schizophrenia was not previously known. This finding
suggests that other molecules which alter the microbiome may be found that are effective as
adjunct therapies for schizophrenia, including ones with less toxicity than valproate
(Haddad, Das, Ashfaq, & Wieck, 2009).
3.2. Studies of intestinal inflammation in schizophrenia and bipolar disorder
Gastrointestinal (GI) pathologies are long-standing comorbidities of psychiatric disorders,
supporting the centuries old hypotheses that gut and brain physiologies are inter-dependent
(Severance, Prandovszky, Castiglione, & Yolken, 2015). In schizophrenia and bipolar
disorder, a low-grade inflammatory state is prevalent in a subset of individuals (Bechter,
2013; Fillman, Sinclair, Fung, Webster, & Shannon Weickert, 2014; Miller, Buckley,
Seabolt, Mellor, & Kirkpatrick, 2011) The origin of this inflammation is not currently well
understood, but recent as well as older studies suggest that it stems from processes related to
dysbiosis of the gut microbiome. This dysbiosis provides a mechanism to generate a GI-
based inflammatory state through the process of microbial translocation of gut microbes into
systemic circulation.
One of the earliest specific documentations of GI inflammation associated with
schizophrenia was a post-mortem study of 82 individuals with schizophrenia, where
researchers found that 50% had gastritis, 88% enteritis and 92% colitis.(Buscaino, 1953)
Interestingly, a converse phenomenon also holds true with reports of psychiatric
comorbidities in people with intestinal disorders which have an inflammatory component.
Prevalence estimates for any psychiatric comorbidity in patients diagnosed with irritable
bowel syndrome (IBS), for example, range from 54–94% (Whitehead, Palsson, & Jones,
2002), and specifically estimates for a schizophrenia comorbidity approach 20%(Gupta,
Masand, Kaplan, Bhandary, & Hendricks, 1997). In a large-scale case-control cohort of
4689 IBS patients and 18756 matched controls without IBS, a diagnosis of IBS increased the
risk for anxiety and mood disorders as well (Lee et al., 2015). Collectively, these
epidemiological studies illustrate that GI inflammation and psychiatric disorders are
connected. However the delineation of the magnitude of the correlation is limited by the
difficulty in making an accurate diagnosis of intestinal diseases in individuals with
psychiatric symptoms and the possible confounding effects of medications.
Dickerson et al.
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Numerous biological indices corroborate a role for GI inflammation in schizophrenia and
bipolar disorder pathophysiology. GI-derived inflammation is often measured based on
biomarkers of the microbial translocation process. The panel of markers used to diagnose
Crohn’s Disease for example includes detection of antibodies to the yeast
Saccharomyces
cerevisiae
, an organism that is part of the normal human gut microbiome (Desplat-Jego et
al., 2007) The presence of antibodies to this yeast indicates that an immune response has
been generated against the organism presumably due to its presence at a potentially
compromised gut mucosa-blood vasculature interface. Elevated antibodies to
S. cerevisiae
were found in individuals with schizophrenia and bipolar disorder and these levels were
particularly increased in individuals experiencing a recent onset of their disorder (Severance
et al., 2012; Severance, Gressitt, et al., 2014). Furthermore, antibody levels were
significantly higher in those with schizophrenia who were antipsychotic-naïve than in those
who were medicated suggesting that the relationship between these disorders and
gastrointestinal inflammation cannot be attributed solely to the effect of antipsychotic
medications. In a follow-up study of a different commensal yeast species,
Candida albicans
,
antibody levels were not only significantly increased in subsets of individuals with
schizophrenia, but were particularly elevated in those who had GI symptoms(Severance,
Gressitt, et al., 2016). In a similar investigation, markers of bacterial translocation were
altered in individuals with schizophrenia and to a certain degree bipolar disorder (Severance
et al., 2013).
The theme for translocation of microbial components into circulation via a breached gut
barrier can be expanded to include other GI-derived substances such as digested foods.
There is a long literature on the anti-milk casein and anti-wheat gluten immune response
associated with schizophrenia and a sensitivity to these foods is known to also generate an
inflammatory response in the intestinal tract (Severance, Yolken, & Eaton, 2014). Finally,
exposure to the neurotropic protozoan pathogen,
Toxoplasma gondii
, is a well-studied risk
factor for the development of schizophrenia(Torrey et al., 2012). Interestingly,
T. gondii
enters and establishes itself in its host via the intestinal tract and is used in experimental
animal models to generate intestinal disorders associated with inflammatory processes
(Bereswill et al., 2010). In human studies, antibodies to this parasite were significantly
associated with markers of food sensitivity in those with schizophrenia (Severance et al.,
2012). Thus, it cannot be ruled out that the association of exposure to this parasite with
psychiatric disorders may be a function of its pathological effects in the gut.
3.3. Study of bacterial infections and antimicrobial agents in acute mania
Bacterial infections are a source of immune activation and have been shown to be a risk
factor for the subsequent development of schizophrenia and mood disorders(Benros,
Mortensen, & Eaton, 2012; Benros et al., 2013; Nielsen, Benros, & Mortensen, 2013)
Consistent with some previous population-based studies (Kohler et al., 2014), a recent study
employed the prescription of antibiotic agents as a measure of bacterial infections. The study
population consisted of 234 individuals hospitalized for acute mania, most diagnosed with
bipolar disorder, in either an inpatient unit or a day hospital and also individuals hospitalized
for schizophrenia, bipolar depression, major depression, as well as non-psychiatric
controls(R. Yolken et al., 2016). The study found that in patients with acute mania, but not
Dickerson et al.
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Brain Behav Immun
. Author manuscript; available in PMC 2017 July 10.
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References
More filters
Journal ArticleDOI
Stephan Ripke1, Stephan Ripke2, Benjamin M. Neale1, Benjamin M. Neale2  +351 moreInstitutions (102)
24 Jul 2014-Nature
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

6,809 citations


"The microbiome, immunity, and schiz..." refers background in this paper

  • ...Within the schizophrenia group, the level of this phage was significantly associated with the presence of immunological disorders such as diabetes, which are common co-morbid conditions in individuals with schizophrenia (Schoepf et al., 2014)....

    [...]

Journal ArticleDOI
13 Sep 2012-Nature
TL;DR: Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.
Abstract: Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time — especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.

3,890 citations

Journal ArticleDOI
TL;DR: Evidence is shown that schizophrenia and bipolar disorder partly share a common genetic cause, which is consistent with a reappraisal of these disorders as distinct diagnostic entities.

1,855 citations


"The microbiome, immunity, and schiz..." refers background in this paper

  • ...Genome-wide association studies show a great deal of genetic overlap between schizophrenia and bipolar disorder (Lichtenstein et al., 2009; Van Snellenberg and de Candia, 2009)....

    [...]

Journal ArticleDOI
TL;DR: Similar effect sizes in AR and FEP suggest that the association between cytokine abnormalities and acute exacerbations of schizophrenia is independent of antipsychotic medications.

1,426 citations

Journal ArticleDOI
TL;DR: Multivariate statistical analyses suggest that gastrointestinal disorders, psychiatric disorders, and nongastrointestinal somatic disorders are distinct disorders and not manifestations of a common somatization disorder, but their strong comorbidity suggests a common feature important to their expression, which is most likely psychological.

1,048 citations