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Daily intake of fermented milk with Lactobacillus casei strain Shirota reduces the incidence and duration of upper respiratory tract infections in healthy middle-aged office workers


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Purpose: Although several studies have demonstrated the efficacy of probiotics for preventing upper respiratory tract infections (URTIs) in at-risk populations, including children and the elderly, few studies have investigated the efficacy of probiotics in healthy adults living normal, everyday lives. Thus, we tried to evaluate the effects of Lactobacillus casei strain Shirota-fermented milk (LcS-FM) on the incidence of URTIs in healthy middle-aged office workers. Methods: In a randomized controlled trial, 96 eligible male workers aged 30-49 years consumed LcS-FM containing 1.0 × 10(11) viable LcS cells or control milk (CM) once daily for 12 weeks during the winter season. URTI episodes were evaluated by a physician via a questionnaire of URTI symptoms. Results: The incidence of URTIs during the intervention period was significantly lower in the LcS-FM group than in the CM group (22.4 vs. 53.2 %, P = 0.002). The time-to-event analysis showed that the LcS-FM group had a significantly higher URTI-free rate than the CM group over the test period (log-rank test: χ (2) 11.25, P = 0.0008). The cumulative number of URTI episodes and cumulative days with URTI symptoms per person was lower in the LcS-FM group, and the duration per episode was shorter. Inhibition of both reductions in NK cell activity in peripheral blood mononuclear cells and increases in salivary cortisol levels was observed in the LcS-FM group. Conclusion: The results suggest that the daily intake of fermented milk with LcS may reduce the risk of URTIs in healthy middle-aged office workers, probably through modulation of the immune system.
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Eur J Nutr (2017) 56:45–53
DOI 10.1007/s00394-015-1056-1
Daily intake of fermented milk with Lactobacillus casei strain
Shirota reduces the incidence and duration of upper respiratory
tract infections in healthy middle‑aged office workers
Kan Shida1 · Tadashi Sato1 · Ryoko Iizuka1 · Ryotaro Hoshi2 · Osamu Watanabe2 ·
Tomoki Igarashi2 · Kouji Miyazaki1 · Masanobu Nanno1 · Fumiyasu Ishikawa1
Received: 10 June 2015 / Accepted: 23 September 2015 / Published online: 29 September 2015
© The Author(s) 2015. This article is published with open access at
mononuclear cells and increases in salivary cortisol levels
was observed in the LcS-FM group.
Conclusion The results suggest that the daily intake of
fermented milk with LcS may reduce the risk of URTIs
in healthy middle-aged office workers, probably through
modulation of the immune system.
Keywords Probiotics · Lactobacillus casei strain
Shirota · Upper respiratory tract infection · Common cold ·
NK cell activity · Cortisol
The human intestinal tract harbors more than 100 trillion
bacteria, and the commensal gut microbiota plays a pivotal
role in maintaining the health of the host [1]. Thus, much
attention has been given to probiotics, which can survive
the intestinal tract and recover/maintain balanced gut
microbiota when ingested orally [2, 3]. Some strains of lac-
tobacilli and bifidobacteria are popular probiotics, usually
consumed as fermented dairy products or supplements [4].
Among the health benefits of probiotics, the prevention or
control of infectious diseases is one of the most promising
targets [5, 6]. Several studies have demonstrated that some
probiotics are effective against not only infections in the
gastrointestinal tract, but also those in the respiratory tract
[7, 8].
Many clinical trials against upper respiratory tract infec-
tions (URTIs), such as the common cold and influenza,
have evaluated various probiotic strains, and many of these
have demonstrated efficacy against URTIs [7, 8]. The tar-
get populations in these clinical trials have generally been
infants, children, students, and the elderly [912]. Since
the immune defenses in these populations are relatively
Purpose Although several studies have demonstrated the
efficacy of probiotics for preventing upper respiratory tract
infections (URTIs) in at-risk populations, including chil-
dren and the elderly, few studies have investigated the effi-
cacy of probiotics in healthy adults living normal, everyday
lives. Thus, we tried to evaluate the effects of Lactobacillus
casei strain Shirota-fermented milk (LcS-FM) on the inci-
dence of URTIs in healthy middle-aged office workers.
Methods In a randomized controlled trial, 96 eligible
male workers aged 30–49 years consumed LcS-FM con-
taining 1.0 × 1011 viable LcS cells or control milk (CM)
once daily for 12 weeks during the winter season. URTI
episodes were evaluated by a physician via a questionnaire
of URTI symptoms.
Results The incidence of URTIs during the intervention
period was significantly lower in the LcS-FM group than
in the CM group (22.4 vs. 53.2 %, P = 0.002). The time-
to-event analysis showed that the LcS-FM group had a sig-
nificantly higher URTI-free rate than the CM group over
the test period (log-rank test: χ2 11.25, P = 0.0008). The
cumulative number of URTI episodes and cumulative days
with URTI symptoms per person was lower in the LcS-FM
group, and the duration per episode was shorter. Inhibition
of both reductions in NK cell activity in peripheral blood
Kan Shida, Tadashi Sato, and Ryoko Iizuka have contributed
equally to this work.
* Kan Shida
1 Yakult Central Institute, 5-11 Izumi, Kunitachi-shi, Tokyo
186-8650, Japan
2 Faculty of Research and Development, Yakult Honsha,
Shinbashi, Tokyo 105-8660, Japan
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46 Eur J Nutr (2017) 56:45–53
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weak, the use of probiotics might be pertinent. However,
few studies have investigated the efficacy of probiotics in
healthy adults [13, 14].
Maintaining the immune defense system within a normal
healthy state lowers the risk of URTIs. NK cell activity and
salivary immunoglobulin A (IgA) are considered important
in the prevention of URTIs [15, 16]. However, several envi-
ronmental factors, including a stressful lifestyle, are likely
to weaken the immune defense system [17], which may
result in an increase in the risk of URTIs. There is some
evidence to suggest that some probiotic strains restore NK
cell activity and salivary IgA levels [1820]. Thus, daily
ingestion of a probiotic beverage might maintain normal
immune function and control URTIs.
Lactobacillus casei strain Shirota (LcS) is a probiotic
that can survive within the intestinal tract and recover bal-
anced gut microbiota [21]. The immunomodulatory activi-
ties of the strain have been studied extensively in animal
models and human studies [18, 22]. Studies in healthy sub-
jects with low NK cell activity showed that ingestion of
LcS-fermented milk (LcS-FM) recovered the activity [18].
Clinical trials have shown that LcS effectively reduces the
risk of bladder cancer and colorectal tumor recurrences,
and it has been proposed that immunomodulatory activi-
ties, including the recovery of NK cell activity, are among
the underlying mechanisms [23]. Therefore, accumulating
evidence implies that this probiotic has potential use as an
immunostimulatory food material.
Some clinical trials with LcS have targeted URTIs. A
double-blind, randomized, placebo-controlled trial in
healthy elderly people attending day care facilities showed
that consumption of LcS-FM reduced the duration of each
URTI episode, but not the incidence rate [24]. Another
trial conducted in healthy elderly nursing home residents
showed a nonsignificant decreasing trend in the incidence
of upper respiratory symptoms via LcS-FM ingestion
[25]. On the other hand, a study conducted among healthy
young athletes of endurance-based sports showed that LcS
was effective in preventing URTIs [20]. In the latter study,
daily consumption of LcS-FM significantly reduced the
incidence of URTIs and the cumulative number of URTI
episodes. Variations in the efficacy of LcS-FM might be
due to differences among study populations.
We think that it is important to evaluate the efficacy of
LcS in normal healthy adults, because events in daily life
can lead to weakened immune defense responses. Thus,
healthy middle-aged office workers were selected for this
study. We measured the effect of the daily consumption
of LcS-FM on the incidence of URTIs as the primary out-
come. Additionally, we analyzed both NK cell activity and
salivary IgA levels as immunological markers, and the lev-
els of cortisol in saliva as a stress marker.
Materials and methods
Healthy male workers living in Tokyo or its suburbs, aged
30–49 years, and working within office buildings were
recruited for this study via Web site advertising. The exclu-
sion criteria were as follows: (1) working outside the office
building twice or more a week; (2) difficulty providing
saliva and blood samples; (3) pollinosis, chronic rhinitis,
asthma, or milk allergy; (4) periodontitis or gingivitis; (5)
history of serious liver, kidney, heart, lung, or gut disease;
(6) receiving current medical treatment; (7) regularly con-
suming probiotics or fermented milk; (8) taking drugs or
supplements that might affect the outcome of the study; (9)
history of influenza vaccination or infection within the last
6 months; and (10) being deemed ineligible for this study
by a physician, based on blood chemistry, blood pressure,
pulse rate, or other reasons.
Participants were given a detailed explanation of the
purpose and potential risks of the study, and 217 workers
provided written consent and participated in a screening
test, in which blood, urine, and saliva analysis, a physical
examination, measurements of blood pressure and pulse,
and a questionnaire regarding lifestyle and working pro-
file were performed. Seventy-eight participants met the
exclusion criteria, 10 with salivary IgA concentrations of
509 μg/ml or more were excluded, and 29 declined to par-
ticipate prior to allocation. The remaining 100 participants
were randomly allocated to two groups: the LcS-FM group
and the control milk (CM) group.
Sample size calculation
The sample size was calculated by assuming that the inci-
dence of URTIs during the test period of 12 weeks would
be 80 % and LcS-FM would reduce the incidence by 35 %
[13, 20, 26]. At a significance level of 0.05 with 80 %
power, it was estimated that 44 participants were needed
per group to detect significant differences between the
groups by the Chi-square test. Thus, 100 participants were
included in this study.
Study design
We conducted a randomized, controlled trial from December
8, 2012, through March 5, 2013, at the Chiyoda Paramedi-
cal Care Clinic (Tokyo, Japan). The study was conducted
according to the guidelines laid down in the Declaration of
Helsinki. All procedures were approved by the Institutional
Review Board of the Chiyoda Paramedical Care Clinic. Writ-
ten, informed consent was obtained from all participants.
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47Eur J Nutr (2017) 56:45–53
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Test drinks
LcS-FM consisted of skimmed milk, high-fructose corn
syrup, sugar, flavoring, and a minimum of 1.0 × 1011 live
LcS cells. Probiotic strain LcS (YIT 9029) was obtained
from the Culture Collection Research Laboratory of the
Yakult Central Institute. Milk was used as a control bever-
age [12]. LcS-FM and CM drinks were placed into plastic
bottles. The test drinks were delivered to each participant
once a week under refrigeration and stored in a refrigerator
until consumption.
Participants were allocated randomly to either the LcS-
FM or CM group. Both groups were asked to consume
one bottle of the test drink every day for 12 weeks and
to refrain from consuming any other probiotic foods and
Participants kept a health diary during the intervention
period each day before bedtime, recording body tempera-
ture, any symptoms of illness, and the impact of any symp-
toms on their daily activities by rating the impact as none/
light, moderate, or severe. The test drinks consumed and all
prohibited foods and supplements were also recorded in the
diary. Participants were also asked to record possible symp-
toms of URTIs on the URTI symptom questionnaire on a
daily basis.
Participants visited the clinic at weeks 0, 6, and 12 dur-
ing the intervention period, and saliva and blood samples
were collected. Participants were free to consult any doctor
of their choice when experiencing symptoms of an illness,
but were required to record the details of any diagnosis pro-
vided, hospital care given, prescribed and non-prescribed
medications taken, and the results of influenza virus tests
via influenza diagnosis kits if applicable in the health diary.
Evaluation of URTIs
URTI episodes were evaluated by a physician at the clinic
based on the information recorded in the health diary, the
URTI symptom questionnaire, and interviews at 6 and
12 weeks after the intervention period commenced [12,
20]. The URTI symptom questionnaire consisted of ques-
tions on the following 16 symptoms: (1) fever; (2) chill;
(3) headache; (4) runny nose; (5) stuffy nose; (6) sneezing;
(7) cough; (8) sore throat; (9) sputum; (10) malaise; (11)
muscular pain; (12) joint pain; (13) nausea; (14) diarrhea;
(15) stomach ache; and (16) itchy eyes. The non-numerical
ratings of none/light, moderate, and severe were scored as
1, 2, and 3, respectively, for each item. The daily symptom
severity score for URTIs was calculated by summing all
the scores for each item, except those for nausea, diarrhea,
stomach ache, and itchy eyes, which were set to distinguish
a URTI episode from gastrointestinal infections and pollin-
osis. Thus, the maximum score for daily symptom severity
was 36. Symptoms separated by more than 2 consecutive
symptom-free days were recorded as separate episodes.
Influenza was diagnosed according to the results of
influenza virus test kits conducted as required at any hos-
pital and was counted as a URTI episode. URTIs other than
influenza were recorded as the common cold.
NK cell activity
Peripheral blood mononuclear cells were freshly isolated,
and NK cell activity was measured by the chromium
release assay using K562 target cells. Peripheral blood
mononuclear cells and 51Cr-labeled K562 cells were incu-
bated at a ratio of 20:1 for 3.5 h, and radioactivity released
from lysed target cells was measured. The percentage of
specific lysis was calculated as NK cell activity using the
following formula: specific lysis (%) = (experimental
release spontaneous release)/(maximal release sponta-
neous release) × 100.
Saliva analysis
Saliva was collected between 09:00 and 11:00 at the clinic
by the passive drool method. Participants were asked to
allow saliva to pool in the mouth for 3 min before transfer-
ring it via a straw to a collection tube. Saliva collection was
repeated four times with 1-min intervals. The pooled saliva
was centrifuged at 1500×g for 15 min, and the supernatant
was stored below 20 °C until analysis.
The levels of secretory IgA and cortisol were deter-
mined by immunoassay kits (Salimetrics, PA) according to
the instruction manuals.
Adverse events
General biochemical and hematological testing of blood,
urinary qualitative examinations, and physiological tests
were performed at 0 and 12 weeks, and the results before
and after the intervention period were compared. Any
adverse health events were recorded by participants in their
health diaries during the intervention period and confirmed
by the clinic physician at weeks 6 and 12.
Statistical analyses
The difference in URTI incidence between the groups
was analyzed by the Chi-square test. Time-to-episode
curves for the first URTI in the groups were described
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48 Eur J Nutr (2017) 56:45–53
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by the Kaplan–Meier method, and the difference was
analyzed by the log-rank test (27). A hazard ratio was
estimated using unadjusted Cox proportional hazard
model. The risk reduction efficacy was calculated using
the following formula: efficacy (%) = (1 hazard
ratio) × 100. Comparisons of the cumulative numbers of
URTI episodes per person and levels of symptom sever-
ity between the groups were performed by the Wilcoxon
two-sample test. Comparisons of cumulative days with
symptoms per person and the durations of URTI epi-
sodes were achieved using the unpaired Student’s t test.
Unpaired and paired Student’s t tests were, respectively,
used for intergroup and intragroup comparisons of NK
cell activity, salivary IgA secretion, and cortisol levels.
Two-tailed P values <0.05 were considered statistically
significant. All analyses were performed using IBM
SPSS software version 20.0 (IBM Japan, Tokyo, Japan)
and SAS software version 8.2 (SAS Institute Japan,
Tokyo, Japan).
Participant flow and characteristics
The participant flow diagram for this study is shown in
Fig. 1. Eligibility was assessed in 217 male workers.
Among them, 100 participants were recruited to the study
and allocated to either the LcS-FM or CM group. One par-
ticipant in the CM group did not start the intervention due
to personal reasons, and 99 participants completed it. Of
the 99 participants, 3 were excluded from the analysis for
the following reasons: one started medication for hyperten-
sion during the intervention period; one consumed prohib-
ited probiotic drinks on 10 days during the test period; and
one was found to meet an exclusion criterion of the study.
Thus, 96 participants comprising 49 participants in the
LcS-FM group and 47 participants in the CM group were
used for data analysis.
The baseline characteristics of the 96 eligible partici-
pants from the two groups are summarized in Table 1. No
significant differences in age, body mass index, living with
a child, smoking habits, or salivary IgA levels were found
between the groups. Both groups showed very good com-
pliance in terms of test drink consumption.
Incidence of URTIs
The primary outcome measure of this study was URTI inci-
dence, the results of which are shown in Table 2. The incidence
rates of URTIs during the intervention period (weeks 1–12)
were significantly different at 53.2 and 22.4 % for the CM
and LcS-FM groups, respectively (P = 0.002). The incidence
rate of the common cold was significantly lower in the LcS-
FM group than in the CM group (18.4 vs. 44.7 %, P = 0.005).
The incidence of influenza was 10.6 % in the CM group and
4.1 % in the LcS-FM group, although this difference did not
Assessed for eligibility (n = 217)
Excluded (n = 117)
-Meeting exclusion criteria (n = 78)
-Having higher sIgA (n = 10)
-Declined to participate (n = 29)
Randomised (n = 100)
Allocated to CM (n = 50)
-Declined to participate (n = 1)
Allocated to LcS-FM (n = 50)
-Declined to participate (n = 0)
Completed (n = 49)
-Analyzed (n = 47)
-Excluded from analysis (n = 2)
Completed (n = 50)
-Analyzed (n = 49)
-Excluded from analysis (n = 1)
Fig. 1 Participant flow diagram for this study
Table 1 Baseline
characteristics of participants
CM control milk, LcS-FM L. casei strain Shirota-fermented milk, BMI body mass index, SIgA salivary
immunoglobulin A
a No. of participants living with one or more children attending elementary/junior high school
b P values analyzed by the unpaired Student’s t test
c P values analyzed by the Chi-square test
CM (n = 47) LcS-FM (n = 49) P value
Mean (SD) n (%) Mean (SD) n (%)
Age (years) 40.5 (5.9) 40.6 (5.3) 0.931b
BMI (kg/m2) 23.6 (2.7) 22.8 (2.8) 0.184b
No. living with a childa17 (36.2) 19 (38.8) 0.792c
No. of smokers 9 (19.1) 16 (32.7) 0.306c
SIgA secretion rate (μg/min) 57.4 (23.7) 50.8 (31.0) 0.245b
Product compliance (%) 99.7 (1.1) 99.7 (0.9) 0.930b
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49Eur J Nutr (2017) 56:45–53
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reach statistical significance. Time-to-episode curves for the
first URTI are shown in Fig. 2. The curve of the LcS-FM group
was significantly higher than that of the CM group over the test
period (log-rank test: χ2 11.25, P = 0.0008). The URTI-free
rates were 0.78 (95 % CI 0.66–0.89) and 0.47 (95 % CI 0.33–
0.61) in the LcS-FM group and the CM group, respectively.
The hazard ratio was calculated 0.32 (95 % CI 0.16–0.65).
We further analyzed the incidence rates of URTIs dur-
ing the following three periods: 1st period (weeks 1–4); 2nd
period (weeks 5–8); 3rd period (weeks 9–12). As shown in
Table 2, the incidence of URTIs was significantly reduced in
both the 1st and the 2nd periods (P = 0.017 and P = 0.049,
respectively) but not in the 3rd period in the LcS-FM group.
Characteristics of URTI episodes
The effects of the test drinks on the cumulative number
of episodes, the cumulative days with symptoms, and the
duration and severity of URTIs were analyzed. The cumu-
lative numbers of URTI episodes per person during the
intervention period were 0.7 in the CM group and 0.3 in
the LcS-FM group (P = 0.004; Table 3). The LcS-FM
group had fewer cumulative days with URTI symptoms
per person during the test period, and the duration of each
URTI episode was shorter compared with the CM group
(P = 0.001 and P = 0.002, respectively). The mean and
peak daily severity scores of URTIs did not differ between
the two groups.
Blood and saliva parameters
Since immune defense mechanisms are important for host
resistance to viral infections, we measured NK cell activ-
ity in peripheral blood mononuclear cells and IgA secre-
tion rates in saliva at weeks 0, 6, and 12 of the interven-
tion period. NK cell activity decreased at week 6 compared
with week 0 in the CM group, but not in the LcS-FM group
(Fig. 3). Thus, NK cell activity was significantly higher
at week 6 in the LcS-FM group than in the CM group
(P = 0.013). Salivary IgA secretion increased in weeks
6 and 12 in both groups, and the secretion did not differ
between the groups.
Table 2 Primary outcomes: incidence of URTIs
URTI upper respiratory tract infection, CM control milk, LcS-FM L.
casei strain Shirota-fermented milk
a No. of participants with URTIs/common cold/influenza
b P values analyzed by the Chi-square test; P < 0.05 is considered
statistically significant
CM (n = 47) LcS-FM (n = 49) P valueb
na (%) na (%)
Whole period (1–12 weeks)
URTIs 25 (53.2) 11 (22.4) 0.002
Common cold 21 (44.7) 9 (18.4) 0.005
Influenza 5 (10.6) 2 (4.1) 0.201
1st period (1–4 weeks)
URTIs 11 (23.4) 3 (6.1) 0.017
Common cold 11 (23.4) 3 (6.1) 0.017
Influenza 0 (0.0) 0 (0.0)
2nd period (5–8 weeks)
URTIs 12 (25.5) 5 (10.2) 0.049
Common cold 10 (21.3) 4 (8.2) 0.069
Influenza 3 (6.4) 1 (2.0) 0.293
3rd period (9–12 weeks)
URTIs 7 (14.9) 6 (12.2) 0.705
Common cold 5 (10.6) 5 (10.2) 0.603
Influenza 2 (4.3) 1 (2.0) 0.484
oporon of subjects
not having an URTI
Time to event (days)
Fig. 2 Kaplan–Meier time-to-event curves for the first URTI. The
URTI-free rates were 0.78 (95 % CI 0.66–0.89) and 0.47 (95 % CI
0.33–0.61) in the LcS-FM (thick line) and the CM (thin line) groups,
Table 3 Secondary outcomes: episode number per person, total days
with symptoms per person, duration and severity of URTIs
URTI upper respiratory tract infection, CM control milk, LcS-FM L.
casei strain Shirota-fermented milk
a P values analyzed by the Wilcoxon two-sample test; P < 0.05 is
considered statistically significant
b P values analyzed by the unpaired Student’s t test; P < 0.05 is con-
sidered statistically significant
c Mean values of daily severity score during the period of each URTI
d Peak values of daily severity score of URTIs
CM (n = 47) LcS-FM (n = 49) P value
Mean (SD) Mean (SD)
Cumulative number of
URTI episodes
0.7 (0.7) 0.3 (0.8) 0.004a
Cumulative days with
symptoms (days)
3.4 (4.3) 1.0 (2.1) 0.001b
Duration per episode
5.0 (2.5) 2.8 (1.6) 0.002b
Mean severity scorec15.8 (2.8) 15.9 (2.6) 0.966a
Peak severity scored18.2 (4.2) 17.4 (3.6) 0.882a
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50 Eur J Nutr (2017) 56:45–53
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Salivary levels of the stress marker cortisol were ana-
lyzed. In contrast to the change in NK cell activity, cortisol
levels were increased at week 6 in the CM group but not
in the LcS-FM group, and the difference was significant
between the groups (P = 0.045).
There were no adverse effects associated with consumption
of the test drinks during the test period, as confirmed by
the physician following examinations of blood and urine,
physiological tests, analysis of health diaries, and inter-
views (data not shown).
This randomized controlled trial conducted in healthy mid-
dle-aged male office workers clearly demonstrated that the
daily intake of probiotic fermented milk, LcS-FM, reduced
the risk of URTIs. The time to first URTI episode analy-
sis showed that the risk reduction efficacy for LcS-FM was
68 % (95 % CI 35–84 %) compared with CM. The analy-
sis of URTI incidence for divided three periods showed that
the positive health effects of LcS-FM were more evident in
earlier test periods. The incidence of the common cold in
the LcS-FM group (18.4 %) during the intervention period
of 12 weeks decreased by more than half compared with
the control group (44.7 %). The reduction in the incidence
of influenza did not reach statistical significance, which
might be due to the low incidence rates of both groups
(10.6 % for the control; 4.1 % for the LcS-FM group). In
addition to the reduced risk for URTIs, LcS-FM reduced
the cumulative number of days with URTI symptoms and
shortened the duration of each episode.
Intervention studies using similar LcS-FM drinks
against URTIs have been conducted previously. The results
obtained from two previous trials in elderly participants
aged over 80 years did not show a significant reduction in
URTI incidence rates [24, 25]. In contrast, the present study
clearly demonstrated that LcS-FM effectively reduced the
risk of URTIs. These results are consistent with the results
of a trial conducted in athletes aged 18–55 years [20]. The
ages of the participants in the latter study were similar to
those in the present study, and thus, the different age groups
among these studies might explain the conflicting results.
Another difference between the present and the previous
studies should be noted. The viable number of LcS cells
ingested daily was a minimum of 1.0 × 1011 cells in this
study, while in the aforementioned studies with elderly par-
ticipants, the numbers of viable cells were 1.3 × 1010 or
4.0 × 1010. In general, a higher number of ingested viable
probiotic cells will tend to lead to a more beneficial out-
come. The dose–response associated with improved effi-
cacy against URTIs has been reported. De Vrese et al. [28]
showed that while the intake of a multivitamin and mineral
tablet containing 5 × 107 viable lactobacillus and bifido-
bacterium cells shortened the duration of common cold
infections, it had no effect on the incidence rate; however,
another study showed that the similar tablet containing
5 × 108 viable probiotic cells reduced the incidence rate
[29]. The relationship between viable LcS cell numbers
and efficacy should be examined and discussed in future
Many probiotic intervention studies that have demon-
strated efficacy against URTIs have been conducted in
infants, children, students, and the elderly [912]. Physi-
cally active individuals, including rugby players and ath-
letes of endurance-based sports, might also be targets for
probiotics [20, 27, 30]. Since immune defense activities are
relatively weak in such populations, they generally experi-
ence more infections. The present study demonstrated that
0w 6w 12w
NK acvity (%)
Corsol (µg/dL)
** *
0w 6w 12w
0w 6w 12w
IgA (µg/min)
** **
** **
Fig. 3 Changes in NK cell activity in peripheral blood mononuclear
cells, IgA secretion rate, and cortisol levels in saliva throughout the
intervention period of 12 weeks. Data are expressed as means ± SD.
Open circles, CM group (n = 47); closed circles, LcS-FM group
(n = 49). *P < 0.05; **P < 0.01 versus week 0 in the same group;
#P < 0.05 versus CM group
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51Eur J Nutr (2017) 56:45–53
1 3
healthy middle-aged office workers are also a promising
target population for probiotics. A clinical trial in employ-
ees at a manufacturing company in Sweden showed that
daily consumption of L. reuteri ATCC 55730 reduced the
incidence of sick leave due to respiratory or gastrointesti-
nal illnesses during the 80 days of intervention [13]. The
efficacy of probiotics was more evident in a subgroup of
shift workers [13, 14]. The present study demonstrated the
efficacy of probiotics in typical desk workers. In general,
such employees work under pressure and stress every day,
which might be a risk factor for lowered immune defenses.
Daily consumption of certain probiotics at higher doses
may prevent disturbances in immune function resulting
from stressful events in daily life. Thus, these results sug-
gested the potential use of probiotics to improve health in
the workplace.
In the present study, LcS-FM consumption led to
improvements in immunological parameters and a stress
marker. At week 6 of the intervention period, NK cell activ-
ity decreased and the salivary levels of cortisol increased in
the control group, but these parameters kept within baseline
levels in the LcS-FM group. NK cells play a very important
role in the prevention of viral infections, including URTIs
[15]. Inhibition of reduced NK cell activity might increase
resistance to URTIs. The reason for the changes in immu-
nological parameters and stress markers in the control
group is not clear. However, the participants were assigned
unusual daily tasks, including the recording of health infor-
mation of many parameters during the intervention period,
which might have affected their immune and endocrine sys-
tems, especially in the first half of the intervention period.
At a later period, the participants might no longer feel
such stress because getting used to the daily tasks and the
parameters might return to the baseline levels. If the case
is true, intake of LcS-FM may prevent decrease in immune
defense activities caused by certain events, rather than aug-
ment their baseline levels. This may be the reason why
improvements in the parameters by LcS-FM intake were
detected only at week 6. In fact, a previous study in healthy
adults with the normal levels of NK cell activity showed
that LcS intake had no effect on their NK cell activity [31].
Previous studies have revealed that the daily consump-
tion of LcS-FM helps to recover low NK cell activity [18].
In vitro studies with human peripheral blood mononuclear
cells suggest that LcS stimulates monocytes/macrophages
to produce IL-12 and augments NK cell activity [32, 33].
The direct regulation of immune function by LcS might be
realized in the present clinical trial, which in turn might
reduce the incidence of URTIs.
LcS-FM may mediate another protective mechanism
whereby the ingestion of the probiotic drink reduces
stress-related host responses. In the present study, LcS-
FM inhibited increases in the levels of the stress hormone
cortisol, which has the ability to decrease NK cell activity
[34]. Some clinical trials with probiotics or prebiotics have
already focused on psychological stress-related decreases
of host defense mechanisms. The prevention of URTIs by
probiotic or prebiotic supplementation among university
students under stress due to final exams was reported [35,
36]. However, in contrast to the present study, the levels of
cortisol were not examined in these trials.
Increasing evidence suggests that probiotics and the
intestinal microbiota affect the nervous system and brain
function [37]. Recently, Tanida et al. [38, 39] showed that
some probiotic strains including LcS suppress the neural
activity of sympathetic nerves in rats. The nervous system
is closely related to the immune system [40]. Future studies
should focus on nervous system-related actions of probiot-
ics as well as their direct immune modulatory activities to
obtain a better understanding of the precise mechanisms of
preventing viral infections via probiotics.
In conclusion, the findings obtained in this study sug-
gest that the daily intake of fermented milk with LcS may
reduce the risk of URTIs in healthy middle-aged office
workers, probably through modulation of the immune
Acknowledgments We thank the staff of the Creative Pioneer for
Clinical Challenge Co Ltd (Tokyo, Japan) for their help with partici-
pant management, sample analysis, and data analysis. We acknowl-
edge Dr. Mitsuhisa Kawai, the Yakult Central Institute, for the calcu-
lation of sample size and the statistical analyses. We also thank the
participants in this study. This study received no specific grant from
any funding agency.
Compliance with ethical standards
Conflict of interest All of the authors are employed by the Yakult
Honsha, which produces fermented dairy products using the probiotic
strain LcS.
Open Access This article is distributed under the terms of the
Creative Commons Attribution 4.0 International License (http://crea-, which permits unrestricted use,
distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
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... The characteristics of the 14 studies included in this review are summarized in Table 1. The most common study design among the sample was the randomized double-blinded placebo controlled trial, [34][35][36][37][38][39][40] followed by open-label randomized controlled trial, 41-43 randomized three-arm parallel design, [44][45][46] and secondary data analysis of a randomized controlled trial. 47 The studies were conducted worldwide. ...
... 47 The studies were conducted worldwide. Half were implemented in Asia (China, 43 Japan, 38,41,42,47 and Iran 44,45 ). The remainder of the studies was performed in Germany, 34,37 Finland, 35 Italy/Albania, 36 Sweden, 40 the United States, 39 and Australia. ...
... The most common occupational group studied was healthcare workers. 34,36,39,41,43,46,47 followed by factory shift workers, 40,44,45 office workers, 38,42 and military personnel. 35,37 One study included a mixed sample of healthcare workers and first responders working in shifts, such as nurses, police, and firefighters. ...
Full-text available
Background: Prolonged and constant stress from work often leads to numerous adverse health effects. In recent years, interest in probiotics, living microorganisms that can benefit their host when consumed in adequate amounts, to aid health and well-being has increased. This scoping review is to systematically evaluate the current state of science on the effects of probiotic supplements on health, stress, and stress-related symptoms among working adults in occupational settings. Methods: We performed a systematic scoping review following the Arksey and O'Malley Framework. Studies that examined the effects of probiotics on workers' health and stress-related indicators/outcomes in occupational settings were included. A comprehensive search was performed from November 2021 to January 2022 using MEDLINE/PubMed, Cochrane Library, CINAHL, PsychInfo, Scopus, and Embase. Results: A total of 14 papers met the inclusion and exclusion criteria. Probiotics consisted primarily of Lactobacillus and/or Bifidobacterium strains in various forms and doses. Three out of eight studies reported statistical differences in inflammatory markers or stress hormone levels between probiotic and placebo groups. Three of six reported reduced respiratory tract infection incidents in the probiotic groups and three out of four studies reported no differences in anxiety and depression between groups. Lastly, three studies found that absenteeism and presentism were lower in probiotic groups compared with placebo groups. Conclusion: The potential benefits of probiotics exist; however, the measurements of outcomes, the types of probiotics used, and the characteristics of the intervention varied across studies. Further research is needed focusing on probiotics' direct and indirect mechanisms of action on the stress response and the standardization of strains and dosing.
... Treatment of mechanically ventilated patients with probiotics reduced the incidence of ventilator-associated pneumonia (VAP) [44,45]. Results from human studies indicate that L. rhamnosus GG, L. casei, L. plantarum, L. casei strain Shirota, B. lactis Bb-12, and B. longum significantly reduced the prevalence of flu-like symptoms, upper respiratory infections, and antibiotic-associated diarrhea by up to 70% [46][47][48]. The probiotics L. reuteri ATCC 55730, L. paracasei, L. casei 431, L. fermentum PCC, and B. infantis 35624 promoted immunomodulatory changes during URTI and GI infection [49][50][51]. ...
Full-text available
COVID-19, which is caused by the RNA virus, SARS-CoV-2, mainly affects the respiratory system and has a varied clinical presentation. However, several studies have shown that COVID-19 can also affect the gastrointestinal (GI) system. Patients can experience various GI symptoms, such as vomiting and diarrhea, and the virus has been detected in the stool samples of patients hospitalized with COVID-19. There have also been rare reports of COVID-19 presenting with isolated GI symptoms and lack of respiratory symptoms, and the virus has also been detected for prolonged periods in the fecal samples of COVID-19 patients. Major alterations in the gut microbiome in the form of depletion of beneficial organisms and an abundance of pathogenic organisms have been reported in the fecal samples of hospitalized COVID-19 patients. Although the US FDA has approved several drugs to manage COVID-19, their efficacy remains modest. So, there is a constant ongoing effort to investigate novel treatment options for COVID-19. Health supplements like probiotics, prebiotics, postbiotics, and synbiotics have been popularly known for their various health benefits. In this review, we have summarized the current literature, which shows the potential benefit of these health supplements to mitigate and/or prevent the clinical presentation of COVID-19.
... They are probiotic microorganisms that may have beneficial effects on a variety of physiological processes, including immune regulation [24]. It also regulates immunity by reducing inflammatory responses via T-lymphocytes [25], Blymphocytes [26], cells of natural killer (NK) [27], in addition to macrophages [28]. Furthermore, Lactobacillus rhamnosus and L. plantarum can significantly result in the creation of pro-inflammatory cytokines such as IL-6 and TNF- [29].Several investigators used ultra violet (UV) radiation as bodily device for induction of mutation in prokaryotes cyclobutene pyrimidine dimers and pyrimidinepyramidone or photoproducts are maximum crucial permutational deoxyribonucleic acid (DNA) lesions brought about through UV radiation. ...
For folic acid production, two LAB Lactobacillus acidophilus (L. acidophilus) in addition Bifidobacterium longum (B. longum) were exposed to UV irradiation for mutagenesis in relation to folate productivity and antiinflammatory activity. The results indicated that, fifty mutants were tested towards their folate productivity, four mutants only have productivity higher than Wild strains G5 and K1 resulted from B. longum with productivity 68.8 and 56.2% of wild type productivity. Likewise, two mutants of L. acidophilus were A2 and C4 with folate productivity 205.2 and 289.3% respectively of Wild type productivity. Results of docking study showed the mode of binding folic acid demonstrated energy binding of of -8.65 kcal/ mol. against DHFR. Folic acid formed four Pi-alkyl, Pi-Pi In addition to Pi-sigma relationships with Ala9, Ile7, Phe34 and Ile60. Additionally, Folic acid interacted with Glu30 and Asn64 through three hydrogen bonds is 1.77, 1.76, In addition to 1.96 Å. The top four UV-mutants was chosen also showed anti-inflammatory activity determined through inhibiting of COX-1 and COX-2 activity higher than both their wild strains and Celecoxib, mutant A2 was the best in inhibiting COX-1 activity at 8.4µg/ml, while mutant C4 was the best in inhibiting COX-2 activity of 0.030 µg/ml. At the level of FolE gene expression, mutant A2 had the highest gene with 1.4fold, followed by mutant K1 with 1.02, then mutant G5 with 0.97 and all these three mutants have expression of gene higher than those of the two genuine strains. It could be concluded that, Bifidobacterium longum and Lactobacillus acidophilus were genetically improved with regard to their folic acid productivity and anti-inflammatory activity through UV mutagenesis, that resulted in four mutants have productivity higher than Wild strains. Also, the four mutants have antiinflammatory activity through inhibiting of COX-1 and COX-2 activity. Molecular docking was performed to confirm theoretically the role of folic acid in DNA synthesis and repair. The results of the docking investigation revealed that the energy binding of folic acid to DHFR was -8.65 kcal/mol. With folic acid, Ala9, Ile7, Phe34, and Ile60 produced four Pi-alkyl, Pi-sigma, and Pi-Pi interactions. Additionally, three hydrogen bonds between folic acid and Glu30 and Asn64, with separations of 1.77, 1.76, and 1.96, were formed.
The viability of probiotics in the gastrointestinal tract is essential because it has an important role in their health benefits. Plasticity is a phenomenon associated with stress tolerance in bacteria, and stress tolerance of probiotic strains can be induced by the use of additives and weak stress. However, some of these processes are difficult to implement in the manufacture of probiotic beverages, and there are few methods that can be easily applied. Co-culture techniques have been used to produce fermented beverages and may impart distinct characteristics through differences in the culture environment compared with those of monoculture. Here, we show that the stress tolerance of a probiotic strain was altered by co-culture with other strains already used in product manufacturing. Stress tolerance in Lacticaseibacillus paracasei strain Shirota was enhanced by co-culture with Lactococcus lactis subsp. lactis YIT 2027 as a result of an earlier pH decrease. Therefore, the stress tolerance was similarly improved in monocultures where pH was manipulated. Strains with improved stress tolerance had an increase in dihydrosterculic acid in the cell membrane, with altered gene transcription in energy metabolism, lipid metabolism, and chaperone genes. Moreover, fermented beverage consumption studies revealed that the probiotics produced through co-culture were significantly more viable in the human gastrointestinal tract than those produced through monoculture. These data suggested that co-culture with specific strains can significantly enhance the viability of probiotic strains in the human gastrointestinal tract. IMPORTANCE The viability of probiotics in the human gastrointestinal tract is important, as some reports indicate that the health benefits of live bacteria are greater than those of dead ones. Therefore, the higher the viability of the probiotic strain, the better it may be. However, probiotic strains lose their viability due to gastrointestinal stress such as gastric acid and bile. This study provides an example of the use of co-culture or pH-controlled monoculture, which uses more stringent conditions (lower pH) than normal monoculture to produce probiotic strains that are more resistant to gastrointestinal stress. In addition, co-cultured beverages showed higher viability of the probiotic strain in the human gastrointestinal tract than monocultured beverages in our human study.
The possible effect of probiotics consumption on the symptoms and courses of the common cold, influenza, and influenza-like illness was evaluated via a meta-analysis. Probiotic consumption reduced the incidence of the common cold (odds ratio [OR] = 0.50, 95% confidence interval [CI]: 0.38-0.64, P < .001) and influenza-like illness episodes (OR = 0.24, 95% CI: 0.14-0.40, P < .001) but had no significant effect on decreasing the influenza episodes (OR = 0.91, 95% CI: 0.62-1.35, P = .831). Probiotic supplementation showed a promising beneficial role in the reduction of the episodes and symptoms of the common cold and influenza-like illness.
Full-text available
The 10th International Yakult Symposium was held in Milan, Italy, on 13–14 October 2022. Two keynote lectures covered the crewed journey to space and its implications for the human microbiome, and how current regulatory systems can be adapted and updated to ensure the safety of microorganisms used as probiotics or food processing ingredients. The remaining lectures were split into sections entitled “Chances” and “Challenges.” The “Chances” section explored opportunities for the science of probiotics and fermented foods to contribute to diverse areas of health such as irritable bowel syndrome, major depression, Parkinson’s disease, immune dysfunction, infant colic, intensive care, respiratory infections, and promoting healthy longevity. The “Challenges” section included selecting appropriate clinical trial participants and methodologies to minimise heterogeneity in responses, how to view probiotics in the context of One Health, adapting regulatory frameworks, and understanding how substances of bacterial origin can cross the blood–brain barrier. The symposium provided evidence from cutting-edge research that gut eubiosis is vital for human health and, like space, the microbiota deserves further exploration of its vast potential.
Full-text available
We investigated the efficacy of dietary consumption of Lactobacillus brevis KB290 (KB290) against influenza in humans by a preliminary intervention study on elementary schoolchildren, using a commercially available probiotic drink. Subjects were divided into Groups A and B, and an open-label, parallel-group trial was conducted in two 8-week periods at a 1-month interval in winter 2013/2014. Group A was provided with a bottle of the test drink containing KB290 (about 6 billion colony-forming units) every school day in the first period and had no treatment in the second period, and vice versa for Group B. Epidemic influenza was not observed during the first period and only two of 1783 subjects were diagnosed. In the second period, the incidence of influenza in Groups A (no treatment) and B (provided the test drink) was 23·9 and 15·7%, respectively, and the difference was statistically significant (P < 0·001). The reduction in the incidence of influenza by KB290 consumption was especially remarkable in unvaccinated individuals. This is believed to be the first study to show a probiotic food reducing the incidence of influenza in schoolchildren, although further studies are needed to confirm the effectiveness of the probiotic strain KB290. Significance and Impact of the Study We demonstrated a reduction in the incidence of influenza in 1089 schoolchildren by continual intake of a probiotic drink containing Lactobacillus brevis KB290 (KB290), isolated from a traditional Japanese pickle ‘Suguki’. The effect was especially evident in subjects not inoculated with influenza vaccine. This is believed to be the first report to show reduced incidence of influenza in schoolchildren taking a probiotic food. Further studies are needed to confirm the effectiveness of the probiotic strain KB290, which may be useful in the development of potential anti-influenza agents derived from common foods.
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Autonomic nerves, consisting of both sympathetic and parasympathetic nerves, regulate various bodily functions such as blood pressure, body temperature, glucose metabolism, energy metabolism, and digestion. Our studies in rats and mice have demonstrated that food, flavor, and music affect physiological phenomena via changes in autonomic neurotransmissions. Intestinal injection of Lactobacillus johnsonii La1 (NCC533) suppressed sympathetic nerves that innervate the adrenal gland and kidney of urethane-anesthetized rats, lowering blood glucose and blood pressure levels, and excited the gastric parasympathetic nerve, elevating appetite and body weight. In contrast, intestinal injection of Lactobacillus paracasei ST11 (NCC2461) excited sympathetic nerves that innervate white and brown fat and the adrenal gland, increasing lipolysis and body temperature, and suppressed the gastric parasympathetic nerve, reducing appetite and body weight. Interestingly, we found that the hypothalamic suprachiasmatic nucleus (SCN), a master circadian clock, and histamine receptors in histaminergic neurons play important roles in peripheral autonomic control. To investigate the possible role of SCN and histamine receptors in lactobacilli-mediated pathology, we created an SCN-lesion model and experimented with histaminergic blocker injections. SCN lesion or injection of thioperamide, a histamine H3-receptor antagonist, eliminated the suppression of renal sympathetic nerve activity by NCC533, preventing blood pressure decline, and inhibited the enhancement of the gastric parasympathetic nerve induced by NCC533. In addition, diphenhydramine, a histamine H1-receptor antagonist, abolished the increases in renal sympathetic nerve activity and blood pressure caused by NCC2461. Infradiaphragmatic vagotomy eliminated the suppression of renal sympathetic nerve activity by NCC533, but did not affect the excitation of the renal sympathetic nerve by NCC2461. Collectively, these findings strongly suggest that SCN and histamine neurons are involved in the lactobacilli-mediated pathology of autonomic nerves and related physiological changes through abdominal afferent vagal pathway input to the central nervous system.
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Recent advances in intestinal microbiota research are the background for the appearance of functional foods. Lactic fermentation products are included in the functional foods and classified into 3 groups based on their mechanisms of action: probiotics, prebiotics and biogenics. Probiotics are viable microorganisms, such as lactobacilli and bifidobacteria, that beneficially affect the host by improving the intestinal bacterial balance. Prebiotics are nondigestible food ingredients, such as oligosaccharides and dietary fiber, that beneficially affect the host by selectively stimulating the growth or activities of beneficial intestinal bacteria in the colon and thus improve the health of the hosts. Biogenics are biologically active peptides, including immunopotentiators (biological response modifier: BRM), plant flavonoids, etc. They act directly or indirectly through modulation of intestinal microbiota on the health of the hosts. Thus, functional foods enhance bioregulation such as stresses, appetite and absorption; biodefence, such as immunity and suppression of allergies; prevent diseases, including diarrhea, constipation, cancer, cholesterolemia and diabetes; and suppress aging through immunostimulation as well as suppression of mutagenesis, carcinogenesis, oxidation processes, intestinal putrefaction, and cholesterolemia.
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Recent systematic reviews have reported a positive, although modest, effect of probiotics in terms of preventing common cold symptoms. In this systematic review, the effect of probiotics, specifically Lactobacillus and Bifidobacterium strains, on the duration of acute respiratory infections in otherwise healthy children and adults was evaluated. To identify relevant trials, eight databases, including MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Science Citation Index (SCI) and OAISTER, were searched from inception to 20 July 2012. Details regarding unpublished studies/databases were also obtained from probiotic manufacturers. Study selection, data extraction and quality assessment were carried out by two reviewers. Risk of bias was assessed using criteria adapted from those published by the Centre for Reviews and Dissemination. In this review, twenty randomised controlled trials (RCT) were included, of which twelve were considered to have a low risk of bias. Meta-analysis revealed significantly fewer numbers of days of illness per person (standardised mean difference (SMD) − 0·31 (95 % CI − 0·41, − 0·11), I 2= 3 %), shorter illness episodes by almost a day (weighted mean difference − 0·77 (95 % CI − 1·50, − 0·04), I 2= 80 %) (without an increase in the number of illness episodes), and fewer numbers of days absent from day care/school/work (SMD − 0·17 (95 % CI − 0·31, − 0·03), I 2= 67 %) in participants who received a probiotic intervention than in those who had taken a placebo. Reasons for heterogeneity between the studies were explored in subgroup analysis, but could not be explained, suggesting that the effect sizes found may differ between the population groups. This systematic review provides evidence from a number of good-quality RCT that probiotics reduce the duration of illness in otherwise healthy children and adults.
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Aims/IntroductionPreviously, it was observed that long-term ingestion of a probiotic strain Lactobacillus casei Shirota (LcS) ameliorates insulin resistance and glucose intolerance in rats fed a high-fat diet. In the present study, we examined its possible role in the autonomic nervous system during LcS-induced modulations in glucose and lipid metabolism or cardiovascular functions.Materials and Methods The present study examined the effects of intragastric (IG) LcS injection on autonomic nerve tones in anesthetized rats by electrophysiological method.ResultsWe found that an IG injection of LcS suppressed neural activity of sympathetic nerves supplying the white adipose tissue of urethane-anesthetized rats in a dose-dependent manner, whereas sympathetic nerve outflow to brown adipose tissue was not affected by the IG LcS injection. Furthermore, the IG LcS injection reduced efferent sympathetic nerve outflow to the adrenal gland and liver, but did not alter gastric vagal nerve activity, renal sympathetic nerve activity, as well as mean arterial pressure. To test the involvement of afferent vagal nerves and the abdominal organs, we examined the adrenal sympathetic response to an LcS injection in rats with ablated afferent vagal nerves, and found that the adrenal sympathetic nerve response to LcS was inhibited in vagotomized rats. In addition, we found that oral ingestion of LcS attenuated the hyperglycemic response to glucose loading and blood glycerol levels in conscious rats.Conclusions Our data suggest that LcS might affect tissue-specific autonomic nerves through the afferent vagal nerve pathway to modulate glucose and lipid metabolism.
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Accumulating evidences indicate that some diseases are triggered by abnormalities of the gut microbiota. Among these, immune-related diseases can be the promising targets for probiotcs. Several studies have proved the efficacy of probiotics for preventing such diseases including cancers, infections, allergies, inflammatory bowel diseases and autoimmune diseases. Lactobacillus casei strain Shirota (LcS) is one of the most popular probiotics, benefits of which in health maintenance and disease control have been supported by several science-based evidences. This review summarizes human clinical trials with this probiotic against cancer development and also discusses the possible immunomodulatory mechanisms by which LcS exerts anti-cancer activity.
Acute psychological stress is positively associated with a cold/flu. The present randomised, double-blind, placebo-controlled study examined the effect of three potentially probiotic bacteria on the proportion of healthy days over a 6-week period in academically stressed undergraduate students (n 581) who received Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium bifidum R0071 or placebo. On each day, participants recorded the intensity (scale: 0 = not experiencing to 3 = very intense) for nine cold/flu symptoms, and a sum of symptom intensity >6 was designated as a day of cold/flu. B. bifidum resulted in a greater proportion of healthy days than placebo (P≤ 0·05). The percentage of participants reporting ≥ 1 d of cold/flu during the 6-week intervention period was significantly lower with B. bifidum than with placebo (P< 0·05). There were no effects of B. infantis or L. helveticus compared with placebo on either outcome. A predictive model accounted for influential characteristics and their interactions on daily reporting of cold/flu episodes. The proportion of participants reporting a cold on any given day was lower at weeks 2 and 3 with B. bifidum and B. infantis than with placebo for the average level of stress and the most commonly reported number of hours of sleep. Daily intake of bifidobacteria provides benefit related to cold/flu outcomes during acute stress.
Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders.