Brain, Behavior, and Immunity xxx (2017) xxx–xxx

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Brain, Behavior, and Immunity

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Full-length Article

Correlation between gut microbiota and personality in adults:

A cross-sectional study
Han-Na Kim a, Yeojun Yun a, Seungho Ryu b,c, Yoosoo Chang b,c, Min-Jung Kwon b,d, Juhee Cho b,e,g,
Hocheol Shin b,f, Hyung-Lae Kim a,⇑
a
Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Republic of Korea
b
Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
c
Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
d
Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
e
Department of Clinical Research Design and Evaluation, SAHIST, Sungkyunkwan University, 06351 Seoul, Republic of Korea
f
Department of Family Medicine and Health Screening Center, Kangbuk Samsung Hospital School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
g
Department of Health, Behavior and Society and Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States

a r t i c l e i n f o a b s t r a c t

Article history: Personality affects fundamental behavior patterns and has been related with health outcomes and mental
Received 23 September 2017 disorders. Recent evidence has emerged supporting a relationship between the microbiota and behavior,
Received in revised form 21 December 2017 referred to as brain-gut relationships. Here, we first report correlations between personality traits and gut
Accepted 22 December 2017
microbiota. This research was performed using the Revised NEO Personality Inventory and the sequenc-
Available online xxxx
ing data of the 16S rRNA gene in 672 adults. The diversity and the composition of the human gut micro-
biota exhibited significant difference when stratified by personality traits. We found that personality
Keywords:
traits were significantly correlated with diversity of gut microbiota, while their differences were extre-
Personality
Gut microbiota
mely subtle. High neuroticism and low conscientiousness groups were correlated with high abundance
Brain-gut axis of Gammaproteobacteria and Proteobacteria, respectively when covariates, including age, sex, BMI and
Neuroticism nutrient intake, were controlled. Additionally, high conscientiousness group also showed increased abun-
Conscientiousness dance of some universal butyrate-producing bacteria including Lachnospiraceae. This study was of obser-
vational and cross-sectional design and our findings must be further validated through metagenomic or
metatranscriptomic methodologies, or metabolomics-based analyses. Our findings will contribute to elu-
cidating potential links between the gut microbiota and personality, and provide useful insights toward
developing and testing personality- and microbiota-based interventions for promoting health.
Ó 2017 Published by Elsevier Inc.

1. Introduction gastrointestinal function by stress and emotions (Cannon, 1929),

Personality affects fundamental behavior patterns and has been
related with health outcomes in mental disorders. Recently,
computer-based personality judgments using Facebook Likes can
be predictive of behavioral outcomes such as substance use and
physical health (Youyou et al., 2015). There is considerable
research showing that the gut microbiota can influence all aspects
of physiology, including gut-brain communication, brain function,
and behavior (Allen et al., 2017; Cryan and Dinan, 2012). Behaviors
constitute an important element in bidirectional communication
between the gut and brain. Top-down modulation of
⇑ Corresponding author at: Department of Biochemistry, School of Medicine,
Ewha Womans University, 1071, Anyangcheon-ro, Yangcheon-gu, 07985, Seoul,
Republic of Korea.
E-mail address: hyung@ewha.ac.kr (H.-L. Kim).
bottom-up signaling from visceral afferents to the brain in abdom-
inal pain syndromes, and possible regulation emotion (James,
1884) have been reported (Mayer, 2011). Although a link between
the gut microbiota and anxiety, stress, and depression-related
behaviors has recently been established in mice (Dinan and
Cryan, 2012; Neufeld et al., 2011; Park et al., 2013), limited infor-
mation is available from human studies. This may be due to the
complexity of studying the human microbiota, which is affected
by variations in diet, environmental influences, gender-related dif-
ferences, and difficulty of measuring subtle biological changes in
human emotional and cognitive function (Mayer et al., 2015).
Investigating the dynamics of behavior-gut associations in adults
is important because the gut microbiome is practically stable in
healthy adults and the microbiome plays a role in the maintenance
of a healthy state in adulthood (D’Argenio and Salvatore, 2015).

https://doi.org/10.1016/j.bbi.2017.12.012
0889-1591/Ó 2017 Published by Elsevier Inc.

Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
2 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
Although limited, few studies have described a microbial influ-
ence on emotional behaviors in healthy human subjects (Tillisch
et al., 2013) and have been suggested to play a role in depression
(Naseribafrouei et al., 2014) and schizophrenia (Dinan et al.,
2014). Naseribafrouei et al. have reported the order Bacteroidales
was overrepresented, while the family Lachnospiraceae was
underrepresented with respect to operational taxonomic units
(OTU)’s associated with depression (Naseribafrouei et al., 2014).
Changes in the microbiota of autistic patients have been reported
(Cao et al., 2013), but studies of the gut microbiota in children with
autism have been also very limited with small sample sizes. How-
ever, several studies repeatedly report a high co-morbidity of aut-
ism spectrum disorders with gastrointestinal symptoms (Dinan
et al., 2015). Recent reports of trials using probiotics in healthy
human subjects demonstrated improvements in depression or
anxiety outcome measures (Messaoudi et al., 2011). These results
indicate that gut bacteria could have therapeutic potential for
mental health. Despite several lines of evidence correlating gut
microbiota to mental health, we still lack knowledge about the cor-
relation between gut microbiota and mental health including
behavior in humans.
Furthermore, there is a growing body of evidence that gastroin-
testinal symptoms are associated with psychological distress such
as anxiety, depression, and neuroticism (Farnam et al., 2008; Talley
et al., 2001). Personality, as an almost constant characteristic, is a
matter of interest influencing pain duration, severity, and func-
tional impairment in different diseases including irritable bowel
syndrome (IBS) (Farnam et al., 2008). We have reported the genetic
and biologic link between mental health and personality in the
previous study (Kim et al., 2015; Kim et al., 2013). In our previous
study, we found the personality-associated SNPs and biological
pathways which were previously identified in schizophrenia or
other neuropsychiatric disorders, suggesting common genetic
influences might be shared between psychiatric disorders and per-
sonality traits. Much is known about the relationship of personality
to mental health as well as the genetic link between them
(Salehinezhad, 2012). The importance of personality to psy-
chopathology has been recognized since the beginnings of medi-
cine (Widiger and Smith, 2008). Understanding the role of
personality on gut microbiota can help us understand that of men-
tal health on gut microbiota.
This research examines this relationship within the framework
of the Five-Factor Model of personality, which includes Neuroti-
cism, Extraversion, Openness to Experience, Agreeableness, and
Conscientiousness using the Revised NEO Personality Inventory
(NEO PI-R) (McCrae and Costa, 2003). Generally, personality refers
to characteristics that account for consistent patterns of person’s
feelings, thinking, and behavior. These five major dimensions of
personality describe the differences between individuals in the
cognitive, emotional, and social aspects of individual’s behavior
(Heinstrom, 2003). Of the five factors, Neuroticism and Conscien-
tiousness have been associated with physiological risk factors for
morbidity and mortality (Sutin et al., 2010b). More generally, per-
sonality traits are thought of as risk factors, diagnostic indicators,
and predictors of onset, severity, and outcome for most psychiatric
disorders (Terracciano et al., 2010). As a psychological factor, the
role of personality has been suggested in the development or exac-
erbation of gastrointestinal disorders including gastrointestinal
inflammation (Tanum and Malt, 2001). In addition, personality
has been linked to regulations in the hypothalamic-pituitary-
adrenal (HPA) axis activity, as well as to a pro-inflammatory cyto-
kine response (Hill et al., 2013; Sutin et al., 2010a), providing a
rational basis by which personality may be associated with gut
microbiota.
In the present study, we aim at identifying correlations between
human gut microbiota and personality. To elucidate the correla-
Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
tions, we used an explorative approach involving sequencing of
16S rRNA gene amplicons. We analyzed a large population cohort
of 672 adults between the ages of 23 and 69. In this exploratory
investigation, we hypothesized that adults might differ in their
gut microbial compositions based on their personality traits.
2. Material and methods
2.1. Subjects
Participants were recruited from the Kangbuk Samsung Health
Study, which is a cohort study of Korean men and women who
undergo comprehensive annual or biennial examinations at the
Kangbuk Samsung Hospital Healthcare Screening Center in South
Korea. The stool samples were collected from 1463 adult partici-
pants (men: 907, women: 556) between the ages of 23 and 78
who underwent a comprehensive health checkup between Jun
2014 and September 2014. Within this group, 770 participants
had completed personality and nutrient questionnaires. Height
and weight were measured by trained nurses with the participants
wearing a lightweight hospital gown and no shoes. Height was
measured to the nearest 1 mm using a stadiometer with the partic-
ipant standing barefoot. Weight was measured to the nearest 0.1
kg on a bioimpedance analyzer (InBody 3.0 and Inbody 720, Bio-
space Co., Seoul, Korea). Body Mass Index (BMI) was calculated
as weight in kilograms divided by height in meters squared. This
study protocol was approved by the Institutional Review Board
of Kangbuk Samsung Hospital. Written informed consent was
obtained from all participants after the nature and possible conse-
quences of the studies were explained. All applicable institutional
and governmental regulations concerning the ethical use of human
volunteers were followed during this research.
2.2. Fecal samples and DNA extraction
Fecal samples were immediately frozen after defecation at
20
°C and were placed at
70 °C within 24 h. Within 1 month, DNA
extraction from the fecal samples was performed using the MOBio
PowerSoilÒ DNA Isolation Kit (MO BIO Laboratories, Carlsbad, CA)
according to the manufacturer’s instructions.
2.3. PCR amplification and sequencing of bacterial 16S rRNA gene
Variable V3 and V4 regions of the 16S rRNA were amplified with
the universal primers 341F (50 TCG TCG GCA GCG TCA GAT GTG
TAT AAG AGA CAG CCT ACG GGN GGC WGC AG 30 ) and 805R (50
GTC TCG TGG GCT CGG AGA TGT GTA TAA GAG ACA G GA CTA
CHV GGG TAT CTA ATC C 30 ), with each primer modified to contain
a unique 8-nt barcode index by combination of Nextera XT DNA
Library Preparation kit (Illumina, San Diego, CA). PCR reactions
contained 5 ng/lL DNA template, 2  KAPA HiFi HotStart Ready
Mix (KAPA Biosystems, Wilmington, MA) and 2 pmol of each
primer. Reaction conditions consisted of an initial incubation at
95 °C for 3 min, followed by 25 cycles of 95 °C for 30 s, 55 °C for
30 s, and 72 °C for 30 s. Samples were subjects to a final extension
incubation at 72 °C for 5 min. After PCR clean-up and index PCR,
sequencing was performed on the Illumina MiSeq platform accord-
ing to the manufacturer’s specifications (Fadrosh et al., 2014;
Kozich et al., 2013). The 100 bp of overlapping paired-end reads
were merged using pandaseq (version 2.7). To analyze the 16S
rRNA gene sequence, quality filtering, including determination of
the sequence length (>300 bp), end trimming, and determination
of the number of ambiguous bases and the minimum quality score
was performed using Trimmomatic (version 0.32).
 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx 3

2.4. Sequence analysis using QIIME regression analysis for alpha diversity and personality and for the
regression analysis for microbiota abundance and personality.
Chimera was detected and removed using USERCH 6.1 within
QIIME package (version 1.9) (Caporaso et al., 2010). To identify 2.7. Inclusion and exclusion criteria
OTUs from the non-chimeric sequences, an open-reference OTU
picking approach was performed using representative sequences All participants who met any of the exclusion criteria as
with pre-assigned taxonomy from Greengenes (version 13_8). This described were not enrolled in this study (Fig. 1). We excluded
analysis was performed in QIIME, with a 97% similarity threshold. 141 participants because they had used: antibiotics within 6 weeks
In an open-reference OTU picking process, reads are clustered prior to enrollment (N = 55), cholesterol-lowering medications
against a reference sequence collection, and any reads that do (N = 74), or probiotics (N = 19) within 4 weeks prior to enrollment.
not hit the reference sequence collection are subsequently clus- Additionally, two samples with <1,000 sequences per sample were
tered de novo. The initial data set for all 1463 samples included excluded. The number of quality control (QC)-passed sequences
278,619 OTU, and the sequencing depth ranged from 38 to and the Good’s coverage per sample are presented in Supplemen-
137,059 reads per sample (mean = 24,644, SD = 17,384). OTUs with tary Table S2. Additionally, we excluded participants who were
a number of sequences < 0.005% of the total number of sequences diagnosed with mental disorders, such as depression and panic dis-
were discarded by recommendation of Navas-Molina et al. (Navas- order (N = 15). Subjects were included only if complete personality
Molina et al., 2013) for downstream analysis, resulting in 1011 and nutrient intake data were available. In total, 672 subjects were
OTUs. included in the study (male: 412, female: 272). Ages ranged from
23 to 69 years (M = 44.24; SD = 8.39). The sequencing depth
2.5. Personality assessment ranged from 1586 to 119,429 reads per sample (mean = 25,924,
SD = 19,587) and 1011 OTUs.
Personality traits were assessed using the Korean version of the
Revised NEO Personality Inventory (NEO PI-R) (Costa and McCrae,
2.8. Statistical analysis
1992), a 240-item measure of the five factors of personality (PSI
Consulting Corp., Seoul, Korea). The Korean version of the NEO
Basic statistical analyses were performed using SAS (version
PI-R has been used in the Korean population with good reliability
9.3). Exploratory and differential taxa abundance analyses were
and validity (Ahn and Chae, 1997). This instrument has a robust
conducted in RStudio (version 0.98.983) using packages phyloseq
factor structure that has been replicated in >50 other cultures
1.14.0 (McMurdie and Holmes, 2013) and QIIME (version 1.9). To
(McCrae et al., 2005) including Korea (Ahn and Chae, 1997;
perform downstream analyses, the OTU matrix is normalized to
Piedmont and Chae, 1997). It measures 30 facets, six for each of
account for uneven read depth that was a result of sequencing
the five major dimensions of personality. Items were answered
techniques. The normalization was performed using cumulative
on a 5-point Likert-type scale with responses ranging from
sum scaling (CSS) normalization of metagenomeSeq-package
‘‘strongly disagree” to ‘‘strongly agree.” The scores of each person-
(Paulson et al., 2013) for the abundance counts in QIIME. The
ality dimension were computed by summing up 48 items that
OTU data set was not filtered further because many richness esti-
compose each five factor after reversing negatively keyed items.
mates are modeled on singletons and doubletons in the abundance
The Cronbach’s alpha coefficients for neuroticism, extraversion,
data (McMurdie and Holmes, 2013). Several alpha diversity mea-
openness, agreeableness, and conscientiousness were 0.87, 0.86,
sures were estimated based on identified OTUs. Microbial richness,
0.78, 0.76, and 0.84, respectively. Raw scores of each dimension
which measures the number of distinct OTUs in each sample, was
were converted to T-scores (mean = 50, standard deviation = 1),
examined by calculating the Chao 1 index, which is the predicted
which was calculated sex-separately with the normative data of
Korean (male: 1856, female: 1728, PSI Consulting Corp., Seoul,
Korea) because gender differences in personality traits have been
established (Costa et al., 2001). For qualitative analysis, high and
low groups were defined by quartile within 672 subjects; the
low group with T-scores in the first quartile (25th percentile)
and the high group T-scores in the fourth quartile (75th per-
centile) in T-scores. We choose low groups of personality traits
as the reference category for extreme personality groups.

2.6. Dietary assessment

Dietary consumption was assessed using a 103-item self-

administered food frequency questionnaire (FFQ) designed for
use in Korea (Ahn et al., 2007). This validated FFQ was designed
to measure subjects’ usual consumption of foods and food groups
during the previous year. Data were collected on the same day at
the health checkup. The variables selected for this study were total
energy intake and energy-adjusted intakes of carbohydrate, fat,
protein, and fiber using the residual method (Willett et al., 1997).
Only subjects within ±3 standard deviations of the mean value of
the log-transformed energy intake were included in the study. To
avoid collinearity among independent variables, energy-adjusted
intake of fat as covariate was excluded from the analysis because
the intake of fat was showed high correlation (Pearson correlation
coefficient >0.6) with intake of carbohydrate and protein (Supple- Fig. 1. Sample selection procedure. Some participants were excluded for multiple
mentary Table S1). These variables were used as covariates in the criteria.

Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
4 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
number of taxa in a sample by extrapolating out the number of rare
organisms that may have been missed due to undersampling (Cho,
1984). The Shannon, which aims to measure diversity by account-
ing for evenness (Jost, 2007), and the actual number of different
taxa observed in a sample (‘‘Observed”) were used. Additionally,
alpha diversity was also measured with a phylogenetic diversity
measurement, Faith’s PD, often referred to as PD (Faith and
Baker, 2006). The Mann-Whitney U test was used to estimate the
median of the difference between two groups. Equal variances
can be tested using the Levene’s test (Supplementary Table S4).
The general linear model analysis was used to examine the associ-
ations between the dependent variable, alpha diversity, and the
independent variables, each personality domain adjusted for age,
gender, BMI, total energy intake, and energy-adjusted intakes of
carbohydrate, protein, and fiber. To determine the dissimilarity
between the communities’ membership and structure, weighted
UniFrac distances (Lozupone et al., 2011) and Bray-Curtis dissimi-
larity (Bray and Curtis, 1957) and were used as phylogenetic and
non-phylogenetic methods, respectively. The weighted UniFrac
distance matrices account for the actual abundances of the OTUs.
The Bray-Curtis dissimilarity is robust to the presence of zeroes
in a count table, as often is the case for microbiome data. Beta
diversity indices were calculated after application of CSS normal-
ization in QIIME. The tests of significance were performed using
two-sided Student’s t-test. The nonparametric p-values were calcu-
lated using 10,000 Monte Carlo permutations.
Relationships between the abundance of one or more OTUs and
personality traits were examined. Generalized linear models
implemented in multivariate association with linear models
(MaAsLin) packages (Morgan et al., 2012) of RStudio were used
for quantitative and qualitative analysis of each personality
domain. MaAsLin is a multivariate statistical framework that finds
associations between clinical metadata and microbial community
abundance. Here, MaAslin was used to detect associations between
microbiome composition and each personality domain, consider-
ing the effects of other variables (confounders) in the study popu-
lation (i.e., age, sex, BMI, total energy intake, and energy-adjusted
intakes of carbohydrate, protein, and fiber). All analyses in MaAslin
were performed using the default options. We used the zero-
inflated regression model on a gaussian distribution for zero-
inflated microbiota data. The resulting p-values were corrected
for multiple comparisons on each phylogenetic level and each
personality trait using Benjamini-Hochberg correction (FDR). A
q < 0.05 was considered statistically significant. To detect bacterial
taxa with significantly different abundances between low and high
groups of each personality domain, Linear Discriminant Analysis
(LDA) Effect Size (LEfSe) (Segata et al., 2011) analysis was used
according to the online protocol without adjusting for covariates
(https://huttenhower.sph.harvard.edu/galaxy/).
To validate the correlations between gut microbiota and per-
sonality, we compared our results of the open-reference OTU pick-
ing algorithm to three algorithms which were the closed-reference
OTU picking algorithm using the QIIME 1.9.0, UPARSE (Edgar,
2013), and DADA2 (Callahan et al., 2016). The open-reference
OTU picking combines closed-reference OTU picking, in which
input sequences are aligned to pre-defined cluster centroids in a
reference database, and if the input sequence does not match
any reference sequence at a defined percent identity threshold,
the sequence is excluded, and de novo OTU picking is applied to
the remaining sequences. The OTU picking algorithm used by
UPARSE does not require technology- or gene-specific parameters
(such as an OTU size cutoff), algorithms (such as flowgram denois-
ing) or data (such as a curated multiple alignment) (Allali et al.,
2017). DADA2 is a method to infer the sample sequences in a col-
lection of amplicon sequencing reads and a de novo method of
reference-free. DADA2 does not create OTUs, it infers sample
Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
sequences exactly, resolving differences of as little as one nucleo-
tide (Callahan et al., 2016).
Additionally, microbial community function was evaluated by
predictive metagenome (microbial DNA) analysis using PICRUSt
(Phylogenetic Investigation of Communities by Reconstruction of
Unobserved States) version 1.0.0-dev. PICRUSt is a recently devel-
oped phylogeny-based computational tool that predicts the func-
tional capacity of microbial communities by correlating the
species present to reference databases of microbial genomes
(Langille et al., 2013). OTUs were normalized by 16S rRNA copy
number, and KEGG (Kyoto Encyclopedia of Genes and Genomes)
orthologs (KOs) were predicted. Results that aggregated to level
3 of the KEGG analysis module were further explored with STAMP
(Statistical analysis of taxonomic and functional profiles) version
2.1.3, using the two-group analysis module.
3. Results
3.1. Demographics and collection of 16S data
Descriptive statistics for the participants are shown in Table 1.
To characterize the composition and structure of the gut micro-
biota, 17,421,520 sequences were generated after quality filtering
from 672 samples. On average, 25,925 ± 19,587 sequences were
recovered per sample. We also performed the Good’s coverage test
to test whether the read depth was sufficient for reliable analysis.
The coverage range of samples was 0.951–0.999 (Supplementary
Table S2). It indicates that the read depth was sufficient for reliable
analysis. There is no correlation between the sequence depths and
continuous personality traits and there is no difference in the aver-
age of sequence depths between personality groups (Supplemen-
tary Table S3). We examined differences in microbial diversity
using both quantitative and qualitative measures of each personal-
ity trait.
3.2. Gut microbial diversity: Alpha and beta diversity
Alpha diversity metrics showed that the group with high Open-
ness had greater richness than the low Openness group (Observed;
p = .03, Chao 1 index; p = .03, Mann-Whitney U test) as shown in
Fig. 2A and Supplementary Table S5. There were no differences in
alpha diversity measures incorporating evenness of microbial taxa
and in phylogenetic diversity (Shannon index; p = .42, PD; p = .07,
Mann-Whitney U test). Other personality dimensions did not exhi-
bit differences alpha diversity between the high and low groups of
each dimension. In quantitative analysis for alpha diversity, we
could also confirm consistent results for the Openness dimension.
We found positive correlations between Openness and phyloge-
netic diversity (PD; p = .05, general linear model) as well as richness
(Observed; p = .03, Chao 1; p = .02, general linear model) (Fig. 2B)
when covariates were controlled. Agreeableness was positively cor-
related with Shannon index, while the effect was very small (coeffi
cient = 0.007, p = .02, general linear model) (Supplementary Fig. S1.
C and Supplementary Table S6). Additionally, the moderating effect
of sex on the correlations between personality and alpha diversity
was not found (Fig. 2B and Supplementary Table S6).
To quantify beta diversity, both phylogenetic and non-
phylogenetic methods were used with weighted UniFrac and Bray-
Curtis distances, respectively. The mean weighted UniFrac and
Bray-Curtis within the same Neuroticism group distances (i.e.
within-low group, as well as within-high group) were significantly
lower than between group distances (nonparametric P < .001, two
sample t-test via 100,000 Monte Carlo permutations; Fig. 2C
and D, Supplementary Table S7). This indicates lower diversity and
closer similarity within Neuroticism group paired samples (versus
 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx 5

Table 1
Descriptive statistics of the study participants.

Overall Male Female p-value

The number of samples N = 672 N = 409 N = 263
Age, year, mean (SD)a 44.24 (8.39) 44.62 (8.49) 43.65 (8.20) .15
min:23, max:69 min: 23, max:69 min: 23, max:69
BMI, kg/m2, mean (SD)a 23.62 (3.08) 24.71 (2.79) 21.94 (2.74) <.001
Total energy intake, kcal/d, mean (SD) 1524.51 (608.15) 1630.76 (607.68) 1359.27 (571.94) <.01
Carbohydrate, g/d (SD)a 258.64 (104.43) 268.95 (102.10) 242.61 (106.17) <.01
Protein, g/d, mean (SD)a 51.04 (22.99) 53.20 (23.14) 47.69 (22.41) <.01
Fat, g/d, mean (SD)a 28.41 (18.27) 29.58 (18.51) 26.59 (17.77) .04
Fiber, g/d, mean (SD)a 12.56 (6.50) 12.30 (5.83) 12.95 (7.43) .23
Personality [Raw summed-score (scale rage 48–240), T-score (mean: 50, SD: 10)]
a
Neuroticism (N), mean (SD) 126.66 (20.95) 122.65 (20.59) 132.88 (19.99) <.001
N T-score, mean (SD)a 47.48 (9.40) 47.62 (9.81) 47.27 (8.74) .64
N group, number (% of High)b 318 (31.76) 194 (33.51) 124 (29.03) .40
Extraversion (E), mean (SD)a 160.79 (20.53) 162.31 (20.04) 158.41 (21.08) .02
E T-score, mean (SD)a 50.03 (9.90) 50.30 (9.58) 49.61 (10.39) .38
E group, number (% of High)b 318 (50.00) 190 (51.58) 128 (47.66) .49
a
Openness (O), mean (SD) 150.86 (15.98) 151.99 (15.47) 149.11 (16.62) .02
a
O T-score, mean (SD) 48.06 (10.07) 48.28 (9.82) 47.71 (10.46) .47
b
O group, number (% of High) 348 (35.92) 206 (35.92) 142 (35.92) 1
Agreeableness (A), mean (SD)a 166.74 (13.10) 165.84 (13.61) 168.14 (12.16) .03
A T-score, mean (SD)a 54.04 (8.92) 53.94 (9.34) 54.21 (8.22) .70
A group, number (% of High)b 325 (80.31) 199 (78.89) 126 (82.54) .42
Conscientiousness (C), mean (SD)a 176.25 (17.95) 178.07 (17.03) 173.42 (18.98) <.01
a
C T-score, mean (SD) 53.01 (9.55) 52.93 (9.24) 53.15 (10.03) .77
b
C group, number (% of High) 302 (70.86) 182 (70.33) 120 (71.67) .80

Mean (standard deviation, SD) and p-value from t-test are shown.
a
Quantitative variable. Mean (standard deviation) and p-value from t-test are shown between male and female.
b
Nominal scale. Frequency (percentage) and p-value from v2 test are shown.

between-group). The difference between within- and between-
group similarity was the highest in Conscientiousness using the
weighted UniFrac distance (nonparametric p < .001) but the mean
Bray-Curtis was not statistically significant (nonparametric
p = .56), indicating samples within-Conscientiousness group were
phylogenetically related. Against expectation, gut microbiota dis-
similarity was higher within groups for Openness and Agreeable-
ness than between them because the weight UniFrac distances
within low group of Openness and within high group of Agreeable-
ness were higher than those between group (Supplementary Fig. S2).
3.3. Correlations of gut microbial composition with personality scores
To identify specific microbial taxa significantly correlated with
personality traits while accounting for age, sex, BMI, and dietary
factors, we performed a MaAsLin analysis. We performed the anal-
ysis between each domain of personality traits with taxa repre-
senting >0.01% of total microbial composition and present in at
least >10% of all samples. In quantitative analysis using continuous
T-score, MaAsLin analysis identified 16 candidate taxa correlated
with personality traits, when a false discovery rate of q < 0.25
was applied (Supplementary Table S8), the threshold employed
in previous microbiome studies that allows compensation for mul-
tiple microbial taxa and comparison adjustments (Morgan et al.,
2012). Among them, six taxa exhibited significant correlations of
q < 0.05 with Neuroticism and Conscientiousness (Fig. 3). Specifi-
cally, Neuroticism was positively correlated with abundance of
the class Gammaproteobacteria (r = 0.006, q = 0.045), the order
Pasteurellales (r = 0.007, q = 0.014), the family Pasteurellaceae
(r = 0.007, q = 0.008), the family Peptostreptococcaceae (r = 0.005,
q = 0.048), and the genus Haemophilus (r = 0.007, q = 0.013) (Fig. 3A).
3.4. Altered gut microbial composition in low and high groups for
personality traits
To get more understandable results, we compared groups pair-
wise using categorical variables for personality measurements
(Fig. 3B). We could also confirm consistent results. Taxa belonging
to the class Gammaproteobacteria and the order Pasteurellales
were more abundant in the high Neuroticism group (q < 0.05)
(Supplementary Table S9). Conscientiousness showed a positive
correlation with abundance of Lachnospiraceae (r = 0.003,
q = 7.56  10
3) in the quantitative analysis and this significance
held in the qualitative analysis (r = 0.141, q = 7.06  10
5). The
phylum Proteobacteria was significantly decreased in the high
Conscientiousness group (r =
0.135, q = 0.028). This correlation
was suggestive, but not significant, when evaluated using the
T-score in quantitative analysis (r =
0.004, q = 0.124). The results
for Agreeableness differed between quantitative and qualitative
analysis (Supplementary Tables S8 and S9), perhaps because of
the larger number of patients in the high group than the low group.
We could speculate that highly agreeable individuals are more
likely to agree to stool sample collection. Notably, the mean score
of Agreeableness was also the highest among all personality
domains (Table 1). Additionally, we conducted the MaAsLin analy-
ses separately for sex to examine whether observed correlations
were equally present in both sexes (Supplementary Fig. S3). The
direction and trend of effect were equal in both sex although the
significance of correlations could not pass the threshold for multi-
ple comparisons (q < 0.05) except correlations of Neuroticism and
Haemophilus spp. (q = 0.045) and Conscientiousness with the
Lachnospiraceae (q = 0.007) in male.
LEfSe analysis also confirmed that the genus Haemophilus
(including all upper levels from Proteobacteria to Pasteurellaceae)
were significantly enriched in the group with high Neuroticism
(LDA > 3, p < .05) (Fig. 4A). The bacterial groups enriched in low
Neuroticism group were the family Odoribacteraceae and the
genus Odoribacter. Oscillospira, which was not significantly
correlated with Neuroticism T-scores, was also enriched in the
group with low Neuroticism. Oscillospira has been identified at
low frequency in autism spectrum disorders (De Angelis et al.,
2013). Within these Neuroticism- correlated taxa, the phylum
Proteobacteria had the highest LDA score (3.60; p = .015), followed
by Gammaproteobacteria (LDA = 3.51; p = .005). The class

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Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
6 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx

Fig. 2. Comparisons of community alpha diversities and beta diversities for personality traits. (A and B) Alpha diversity was measured by Observed, PD, Chao1, and Shannon
indices between groups with low and high Openness as a qualitative trait (A) and using the T-scores for Openness as a quantitative trait (B). The central line shown in each
box plot indicates the median of the data and whiskers extend to cover the whole range of values. * = p < .05 (A; Mann-Whitney U test, B; general linear models) The detailed
summary statistics are shown in Supplementary Fig. S1, Supplementary Tables S5 and S6. (C and D) Interval plots showing beta diversity within and between groups (mean
and 95% confidence intervals). (C) Weighted UniFrac distances show the significant difference between within-group and between-group distances for Neuroticism,
Openness, Agreeableness, and Conscientiousness. (D) Bray-Curtis distances show significant differences between within-group and between-group distances for Neuroticism
and Openness. *** = p < .001 (two-tailed Student’s t-test using 100,000 Monte Carlo permutations, computed through QIIME’s script make_distance_boxplots.py). The detailed
summary statistics are shown in Supplementary Table S7. (A) The number (#) of samples (Low/High) = Openness (223/125), (B) # of samples = 672, (C and D) # of samples
(Low/High) = Neuroticism (217/101); Extraversion (159/159); Openness (223/125); Agreeableness (64/216); Conscientiousness (88/214).

Gammaproteobacteria was more abundant in the low Extraversion
group (LDA = 3.66; p = .022) (Fig. 4B). In the Conscientiousness
domain, three taxa: the family Lachnospiraceae and its two genera,
Lachnospira (LDA = 3.30; p = .01) and Roseburia (LDA = 3.23;
p = .003), were significantly more abundant in high Conscientious-
ness group (Fig. 4C). The Lacnospiraceae also exhibited the stron-
gest correlation with Conscientiousness (LDA = 3.96; p = .007),
according to the MaAsLin analysis (Fig. 3).
3.5. Validity of correlations of gut microbial composition with
personality
Comparing the results of the open-reference OTU picking algo-
rithm to three algorithms, the only correlation of Conscientious-
ness and the family Lachnospiraceae was significant in the all
algorithm in the qualitative analysis (Supplementary Table S9).
Although not all of the results were not consistently significant

Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx 7

Fig. 3. Significant correlation between personality traits and gut microbiota composition. (A) Quantitative (continuous) analysis. The T-scores of each personality trait was
used as independent variables. The number of samples was 672. The regression coefficients (r) represent the rate of change in abundance of taxa per 1 score of personality
measurements. The detailed information and summary statistics of personality domains with q < 0.25 are shown in Supplementary Table S8. (B) Qualitative (binary) analysis.
The high and low groups were defined by quartile; the low group with T-scores in the first quartile (25th percentile) and the high group T-scores in the fourth quartile
(75th percentile) in T-scores. The central line shown in each notched box plot indicates the median of the data. The number of samples was represented in each notched box
plot. The detailed statistics are shown in Supplementary Table S9. (A and B) The r-coefficient and q-value shown in each plot were determined by MaAsLin analysis. The y-axis
displays the microbial abundance transformed with the arcsine-square root. Outliers defined by Grubbs test (Grubbs, 1950) were removed in the analysis. *The upper taxa
levels of Haemophilus which are the order Pasteurellales and the family Pasteurellaceae were also significantly correlated with Neuroticism in the qualitative and qualitative
analysis. Results of the personality domains with q < 0.05 in either quantitative or qualitative analysis are listed.

Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
8 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx

Fig. 4. LDA effect size (LEfSe) analysis of between two- group differences in gut microbial abundances for personality traits. Taxa are highlighted on the phylogenetic tree
(cladogram) using LEfSe with red and green colors indicating increased abundance in high and low groups of personality, respectively. The forest plot shows the effect size of
significantly enriched taxa in each group of personality. (A) Neuroticism, # of samples (Low/High) = 217/101, (B) Extraversion, # of samples (Low/High) = 159/159, (C)
Conscientiousness, # of samples (Low/High) = 88/214. p__, phylum; c__, class; o__, order; f__, family; g__, genus. * taxa that were also correlated with that group in the
MaASLin analysis. Features with LDA scores > 3 are presented. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of
this article.)

in the all algorithm, the correlation of Neuroticism with the 3.6. Predicted functional metagenome in personality groups
Gammaproteobacteria and the Haemophilus spp., and Conscien-
tiousness with the Proteobacteria were significant in at least three Based on the functionality predictions using PICRUSt and
algorithms (Supplementary Tables S8 and S9). STAMP, differences in the KEGG Orthologs composition between

Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx 9

Fig. 5. Predictions of metagenome functional content correlated with personality using PICRUSt. OTUs were picked using closed-reference picking, as suggested by PICRUSt
(v1.0.0). KEGG pathways were used at the KEGG-Level-3 category. The extended error bar plot (left) and box plot (right) indicate KEGG pathways where two-sided Welch’s t-
test produced a p < .05, adjusted using the Bonferroni method. Confidence intervals were set at 95%. All pathways were more abundant within the gut microbiota of the
groups with high Neuroticism (A) and Agreeableness (B) relative to the respective low groups. The plots were generated using STAMP (v2.1.3). The central line shown in each
box plot indicates the median of the data and star symbols indicate the mean of the data. # of samples (Low/High) = Neuroticism (217/101) and Agreeableness (64/261).

low and high groups for the five personality traits were detected
(Fig. 5). Among the 328 affiliated KEGG pathways, valine, leucine,
and isoleucine degradation pathways were highly enriched in fecal
microbiota of the high Neuroticism group compared with the low
group (p = 8.86  10
3, p-values by Welch’s t-test with Bonferroni
correction). Additionally, pathways related to methane metabo-
lism and chloroalkane and chloroalkene degradation were detected
in high Agreeableness groups (p = 8.80  10
3 and 0.033,
respectively).
4. Discussion
Most notably, the class Gammaproteobacteria (under Pro-
teobacteria, which is a major phylum of Gram-negative bacteria)
was positively correlated with Neuroticism, while the phylum Pro-
teobacteria was high in individuals with low Conscientiousness.
The tendency to experience negative emotions contributes to
chronic inflammation over time (Sutin et al., 2010a) and inflamma-
tion increases bacterial translocation with immune responses to
lipopolysaccharide (LPS) from Gram-negative gut commensal bac-
teria (Maes et al., 2012). This may play a role in the physiology of
Neuroticism and Conscientiousness. Increased gut permeability
and related bacteria translocation may contribute to increased
inflammation in the groups with high Neuroticism or low Consci-
entiousness. In addition, Lachnospiraceae, which were significantly
less abundant in the low Conscientiousness group, are butyrate-
producing bacteria related to anti-inflammatory mechanisms
(Machiels et al., 2014). Besides, the significance was validated in
both the OTU picking and the denoising algorithms. Butyrate
improves the mucosal barrier function of the colon. Moreover,
butyrate exhibits immunomodulatory effects and exhibits anti-
inflammatory properties by downregulating pro-inflammatory
cytokines (Segain et al., 2000). Of the five personality domains,
Neuroticism and Conscientiousness are most often associated with
morbidity and mortality. These domains were also known to be
associated with intermediate markers of health, including inflam-
mation (Luchetti et al., 2014). Neuroticism and Conscientiousness
have been reported to be associated consistently with activation
of the HPA axis (Mangold and Wand, 2006; Sutin et al., 2010a)
and with greater circulating levels of the inflammatory markers
(Sutin et al., 2010a). We also confirmed the high sensitivity C-
reactive protein (hsCRP) and CRP were higher in low Conscien-
tiousness group (Supplementary Table S10). Although this study
was not designed to address microbial function, future studies
incorporating metagenomics, metatranscriptomics, or metabolo-
mics will help to understand the metabolic and immunobiological
role of the gut microbiota in sustaining personality.
A recent study reported that greater sociability was associated
with greater phylogenetic diversity and beta diversity among boys
(Christian et al., 2015). Interestingly, we also found that higher
Agreeableness corresponded to a little higher alpha diversity
(according to the Shannon index) when covariates were controlled
(Supplementary Table S6). Agreeableness is primarily a dimension
of interpersonal tendencies, and an agreeable person is socially
preferable (Costa and McCrae, 1992). We also found that the group
with high Openness showed a little higher richness than the group
with low Openness. The differences, however, were observed in
richness index but not in incorporating evenness or phylogenetic
diversity, indicating the communities dominated by a few abun-
dant taxa. Openness and Agreeableness were showed gut micro-
biota similarity was lower within than between groups. We
cautiously speculate that it might be due to the characteristics of
Openness and Agreeableness. Openness could reflect a greater

Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
10 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
willingness to try new foods (e.g., bitter vegetables), whereas
agreeableness may reflect a greater likelihood to eat what par-
ents ask them to eat, including fruit and vegetables (de Bruijn
et al., 2005). Although associations of the three major nutrients
and fiber intake were statistically controlled in this study, we
could not control eating habits such as fruit and vegetable (FV)
preference. It is obvious that diet has an important influence
on the composition of human gut microbiota (Graf et al.,
2015). Moreover, there is growing evidence that personality
traits influence eating habits and preference. Especially, Open-
ness and Agreeableness consistently predict higher FV consump-
tion among children and adolescents, as well as Openness is a
key predictor of FV consumption in the adult (Conner et al.,
2017). However, it is difficult to emphasize the effects of person-
ality on the diversity of gut microbiota because the effects were
very subtle despite the statistical significance.
We could infer metabolic capacity of microbiota correlated with
personality from functional inference using PICRUSt. Microbial
functions related to the valine, leucine and isoleucine degradation
pathway may play important roles in Neuroticism on the basis of
the PICRUSt analysis. The degradation of branched-chain amino
acids (BCAA) valine, leucine, and isoleucine, as well as fatty acids,
contribute to ATP and energy production for many Proteobacteria
(Kazakov et al., 2009). BCAAs are important nitrogen donors for
synthesis of neurotransmitters, including the excitatory molecule
glutamate and the inhibitory molecule c-amino butyric acid
(GABA) in the brain. Moreover, a dysregulation of the BCAA cata-
bolic pathways that leads to excess BCAAs and their derivatives
results in neural dysfunction (Hutson et al., 2005). BCAA catabolic
pathways are present in many lineages of Gammaproteobacteria
(Kazakov et al., 2009). The positive correlations of Proteobacteria,
including Gammaproteobacteria, Pasteurellales, Pateurellaceae,
and Haemophilus spp., with Neuroticism, might provide a link in
the brain-gut axis. The 16S approach is well suited for analysis of
a large number of samples but offers limited taxonomical and func-
tional resolution. Although shotgun metagenomics offers a more
reliable assessment, it was reported that the level of concordance
between the functional profiles derived from 16S or from shotgun
metagenomics was variable depending on the pathway under con-
sideration and both methods recapitulated general patterns of
abundance (Jovel et al., 2016). The additional experiments are
needed to understand the biochemical and functional conse-
quences of these predictions.
Here, we have presented the results of this first metataxonomic
study of all five major dimensions of personality. Major strengths
of this study include the use of human samples, the large sample
size, and the efforts to adjust for several relevant covariates,
including age, gender, BMI, and diet, as these factors, especially
diet, influence the structure and activity of microbiota residing in
the gut (David et al., 2014). Diet and diet-related changes in gut
microbiota influence the gut-brain axis and may in turn influence
behaviors including anxiety and depression (Luna and Foster,
2015). Though the current study focused on correlations between
personality and gut microbiota, further studies are needed to
examine mediation effects of diet on relationships between per-
sonality and gut microbiota. Although the observed correlations
were equally present in both sex-integrated and -separated analy-
ses, the statistical power was low when analyses were performed
sex-separately. Although the current study used relatively large
sample sizes, the sex-separated sample size may be not sufficient
for this study because of high inter-individual variations in gut
microbiota compositions. The correlation coefficients between per-
sonality and taxa were very small in the quantitative analysis.
However, the coefficient is the rate of taxa-abundance change
per 1 score of personality measurements which are continuous val-
ues. The difference of 1 unit of personality score between individ-
Please cite this article in press as: Kim, H.-N., et al. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain Behav.
Immun. (2017), https://doi.org/10.1016/j.bbi.2017.12.012
uals might be imperceptible in terms of behavior because the
personality is not a disorder but a normal distributed quantitative
trait in a normal population. Considering that personality is a nor-
mal behavior rather than a serious disease, the small effect size of
personality on gut microbiota could be reasonable in our study.
Even if personality traits have a very small effect, identifying them
may lead to insights regarding the underlying brain-gut axis. Per-
sonality traits could influence behaviors such as eating habits or
lifestyles, and such interactions might have a greater effect on
gut microbiota.
The difference of the sequence depths across the sample is a
limitation of our study although the normalization was performed
for uneven sequence depths. The reliability of our findings depends
upon how much the statistical challenges posed by the underlying
community sequence data impact the chosen normalization tech-
niques (Weiss et al., 2017). Recently, Jovel et al. reported that the
taxonomic classification for each type of library at sequencing
depths of 1000 and 50,000 was surprisingly consistent although
the proportion error and its variance decrease with increasing sam-
pling depth (Jovel et al., 2016). We confirmed a taxon and four taxa
showed the consistent significance in both datasets limited with
>1000 and >10,000 reads in the quantitative (Supplementary
Table S8) and qualitative analysis (Supplementary Table S9),
respectively. Comparing with mouse study, gut microbiota compo-
sitions of human showed higher variation between individuals, so
the statistical power might be significantly affected by the sample
size. Therefore, increasing the sample size may be better and
important for statistical power if the read depth is sufficient for
reliable analysis.
Our findings are also needed to verify in geographically and cul-
turally distinct settings. Although multiculturalism has reduced
lifestyle differences between Asian and Western populations, sig-
nificant distinctions persist, including patterns of food consump-
tion, multiple products of gut microbial and host co-metabolism,
and gut microbiota compositions (Lee et al., 2011). For personality,
there are also literatures on intercultural comparisons (Allik and
McCrae, 2006; Hofstede and McCrae, 2004), showing a clear con-
trast of European and American cultures with Asian and African
cultures (Hofstede and McCrae, 2004). If our results can be repro-
duced in other ethnicities, it would greatly enhance understanding
of generalizability and future research directions for the personal-
ity and microbiota. Recently, Christian et al. reported gut micro-
biome composition was associated with temperament in toddlers
(Christian et al., 2015). However, the temperament of toddlers can-
not predict all dimensions of adult personality (Zelazo, 2013),
although many studies have reported relationships between tem-
perament in infants and adult personality (Halverson et al.,
1994). Previous research on behavior and gut microbiota has
focused primarily on animal models, but researchers should be
cautious when extrapolating these findings to humans (Mayer
et al., 2015).
We show that personality traits are correlated with gut micro-
biota composition. Further research is needed to determine the
mechanistic relationship between dimensions of personality and
the gut microbiota. The direction of causality between personality
and microbiota remains unclear because this study was of cross-
sectional design. Nevertheless, we believe our results provide use-
ful insights toward developing and testing personality- and
microbiota-based interventions for promoting health.
Conflict of interest statement
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
 H.-N. Kim et al. / Brain, Behavior, and Immunity xxx (2017) xxx–xxx
Acknowledgments
This research was supported by the Basic Science Research
Program through the National Research Foundation of
Korea (NRF), funded by the Ministry of Science and ICT
(NRF-2014R1A2A2A04006291) and the Ministry of Education
(NRF-2016R1A6A3A11932719). It was also supported by the Korea
Health Industry Development Institute (KHIDI) funded by the
Ministry of Health & Welfare (HI14C0072). It was also supported
with the computing resources by Global Science experimental Data
hub Center (GSDC) Project and Korea Research Environment Open
NETwork (KREONET) in Korea Institute of Science and Technology
Information (KISTI).
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at https://doi.org/10.1016/j.bbi.2017.12.012.
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