The Influence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the Duration and Severity of Symptoms among Individuals with Covid-19

Abstract

Background: Gut microfloral dysbiosis is known to affect the majority individuals suffering with a Covid-19 infection. This study evaluated whether a specific lactobacillus and inulin blend, which aimed to improve gut health, could reduce the severity of early and chronic Covid-19 symptoms. Methods: From May 2020 to May 2021, we evaluated 126 participants with Covid-19, with an average duration of symptoms of 108 days, who were given 30 days of this pre and probiotic capsule within the ongoing UK national Phyto-v study. Symptoms were recorded using the validated Cough Symptom Score, the Subjective Well-Being questionnaire and the Chandler fatigue questionnaire. The group was analysed as a whole and then subdivided into 40 (32%) in an early phase of infection (average symptoms 10 days before baseline) and the 86 (68%) in a chronic phase (average symptoms 120 days before trial baseline). Results: Cough, fatigue and subjective well-being scores significantly improved over the 30 days in both the early and chronic phase cohorts. Participants who were more likely to have gut dysbiosis at trial entry, such as sedentary, hospitalised, older males with GI symptoms, had a statistically significantly better response to the probiotics. Gut symptoms improved in 25 of 31 (82%) who reported them at baseline. Two (1.5%) patients reported mild increased bloating and diarrhoea. Discussion: Following this nutritional intervention, participants had a significant improvement in GI and non-GI symptoms resulting in a meaningful improvement in overall well-being. Although some participants with early disease would have improved spontaneously, such a rapid improvement in the majority who had been experiencing symptoms for over 6 months, was clinically relevant and welcomed, especially among those more likely to have pre-existing gut dysbiosis. Going forward, our research group are now evaluating whether intake of this blend now known as yourgutplus + , could also enhance antibody titres levels post Covid vaccination.

Full text

Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
1Volume 5; Issue 01
Research Article
The Inuence of a blend of Probiotic
Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among
Individuals with Covid-19
Robert Thomas1,2*, Jeffrey Aldous3, Rachel Forsyth4, Angel Chater5,6,
Madeleine Williams7
1Consultant Clinical Oncologist, Bedford & Addenbrooke’s Cambridge University NHS Trusts, UK
2Department of Oncology, Addenbrooke’s Hospital, Cambridge, UK
3Senior Lecturer in Exercise Physiology, Institute of Sport and Physical Activity Research (ISPAR), University of Bedfordshire, UK
4Department of English, Cambridge University, The Old Schools, Trinity Lane, Cambridge, UK
5Professor in Health Psychology and Behaviour Change, University of Bedfordshire, UK
6Director of Institute for Sport and Physical Activity Research (ISPAR), University of Bedfordshire, UK
7Research Manager, The Primrose Research Unit, Bedford Hospital, UK
*Corresponding author: Robert Thomas, Consultant Clinical Oncologist, Bedford & Addenbrooke’s Cambridge University NHS
Trusts, UK
Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and
Prebiotic Inulin on the Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI:
10.29011/2577-1515.100182
Received Date: November 01, 2021; Accepted Date: November 11, 2021; Published Date: November 16, 2021
Abstract
Background: Gut microoral dysbiosis is known to affect the majority individuals suffering with a Covid-19 infection. This study
evaluated whether a specic lactobacillus and inulin blend, which aimed to improve gut health, could reduce the severity of early
and chronic Covid-19 symptoms. Methods: From May 2020 to May 2021, we evaluated 126 participants with Covid-19, with an
average duration of symptoms of 108 days, who were given 30 days of this pre and probiotic capsule within the ongoing UK national
Phyto-v study. Symptoms were recorded using the validated Cough Symptom Score, the Subjective Well-Being questionnaire and
the Chandler fatigue questionnaire. The group was analysed as a whole and then subdivided into 40 (32%) in an early phase of
infection (average symptoms 10 days before baseline) and the 86 (68%) in a chronic phase (average symptoms 120 days before trial
baseline). Results: Cough, fatigue and subjective well-being scores signicantly improved over the 30 days in both the early and
chronic phase cohorts. Participants who were more likely to have gut dysbiosis at trial entry, such as sedentary, hospitalised, older
males with GI symptoms, had a statistically signicantly better response to the probiotics. Gut symptoms improved in 25 of 31
(82%) who reported them at baseline. Two (1.5%) patients reported mild increased bloating and diarrhoea. Discussion: Following
this nutritional intervention, participants had a signicant improvement in GI and non-GI symptoms resulting in a meaningful
improvement in overall well-being. Although some participants with early disease would have improved spontaneously, such a
rapid improvement in the majority who had been experiencing symptoms for over 6 months, was clinically relevant and welcomed,
especially among those more likely to have pre-existing gut dysbiosis. Going forward, our research group are now evaluating
whether intake of this blend now known as yourgutplus+, could also enhance antibody titres levels post Covid vaccination.
Infectious Diseases Diagnosis & Treatment
Thomas R, et al. Infect Dis Diag Treat 5: 182.
https://www.doi.org/ 10.29011/2577- 1515.100182
https://www.gavinpublishers.com/

Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI: 10.29011/2577-1515.100182
2Volume 5; Issue 01
Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
Keywords: Probiotics; Prebiotics; Covid-19; Gut-health;
Long-Covid symptoms; Yourgutplus+
Introduction and Background
As emerging evidence from clinical studies and experience
from managing patients with Covid-19 (Covid) unfolds, the
links between severity of symptoms, mortality and gut microbial
dysbiosis has become increasingly apparent [1-5]. Depleted
healthy strains of commensal bacteria such as Lactobacillus have
been reported in the majority of patients with Covid expressing
Gastrointestinal (GI) symptoms and especially those with
persistent ongoing problems, coined long or chronic Covid [5-11].
Although most Covid cases have a mild self-limiting respiratory
illness, individuals with co-morbidities and conditions, linked to
poor gut health, such as being elderly, those living with obesity
or diabetes do signicantly worse [7,8,11,12]. The authors of
these studies postulated microoral dysbiosis contributes to
symptoms via increased gut inammation, impaired gut wall
integrity which correspondingly leads to systemic inammatory
dysfunction, reduced immune surveillance leading to greater non-
gut symptoms as well [4-6,8,11,12]. In this situation, overgrowth
of less favourable gut bacteria have been found in the systemic
circulation and within pulmonary aspirates leading to an increased
inammatory response, causing cough and breathlessness [13-
17]. Excess inammatory cytokines and pulmonary exudates
are a feature of Acute Respiratory Distress Syndrome (ARDS)
following a viral infection, hence the recently coined term cytokine
storm [13-17]. The link between bowel dysbiosis and lung hyper
inammation has also been well documented in other chronic
respiratory diseases including asthma and chronic bronchitis [18-
20].
In addition to dietary and behavioural measures,
supplementary capsules are a convenient way to increase total
intake of pro and prebiotics, as well as a way to spread their intake
throughout the day. The most widely researched probiotics include
lactic acid producing bacteria such as species of Lactobacillus,
the colonisation of which is enhanced by concomitant intake
with prebiotic soluble bres such as inulin [21,22]. Numerous
interventional studies in humans and animals have shown they can
help improve mircrooral biodiversity, correct GI symptoms such
as bloating and diarrhoea and improve Immune efciency [23-28].
Many of these studies, albeit most needing further conrmation,
have shown they help modify a range of chronic diseases ranging
from obesity, inammatory bowel disease, diabetes, cardiovascular
disease, hypertension, anxiety, depression, osteoporosis and
dementia [21,28-37]. More relevant to this study, intervention
studies have shown regular intake of live probiotics, particularly
Lactobacilli strains, shortened the incidence duration and severity
of upper respiratory tract infections in several studies [38-43].
This includes a summary of interventional studies published in the
Cochrane Database which concluded that probiotics did reduce
the number of symptomatic upper respiratory tract infections [43].
Another meta-analysis of small RCTs suggests that probiotics
decreased the need for invasive mechanical ventilation due to
development ARDS following viral pneumonia [44].
The reported mechanism of action of probiotic bacteria is
multifactorial [45,46]. They encourage gut colonisation of anti-
inammatory strains, which then out space pro-inammatory
(Firmicutes) bacteria. They encourage the fermentation of
otherwise poorly digestible dietary carbohydrates into Short-Chain
Fatty Acids (SCFA) such as butyrate. These have an important
impact upon mucosal physiology, as they are an idea source of
energy for gut cells so help improve gut health and hence gut wall
integrity [45,47-49]. Probiotic bacteria also help the breakdown
of polyphenols into more ready absorbed and more bioactive
varieties [50,51]. Higher serum levels of polyphenols and other
phytochemicals are linked to lower systemic inammation, a
lower risks of chronic degenerative disease [48,51-56] and cancer
[52,53].
As well as their positive inuence on immune balance,
probiotics have been found to have a range of other potential
mechanisms of actions [45,46]. They can enhance intracellular
oxidative enzyme capacity and can help scavenge excess superoxide
anions among patients with Covid [57]. This mechanism, in
laboratory studies, was attributed to their ability to reduce
oxidative stress via upregulating superoxide transferase and other
anti-oxidant enzymes [58,59]. Excess oxidative stress is a linked
to more aggressive pulmonary pathogenicity following Covid
pneumonia [60,61]. Probiotics help increase vitamin D absorption
and bioactivity [62-66]. Low vitamin D is associated with higher
levels of unregulated hyper inammatory cytokine production and
ultimately more severe respiratory Covid related symptoms [67-
70]. Finally, there are reports of direct anti-viral actions of lactic
acid producing bacteria such as lactobacillus via the production
of antiviral inhibitory metabolites following induction of the
expression of genes involved in antiviral immunity [71-75].
The Kings App study has reported that individuals, who
have more symptoms initially, including bowel problems, were
more at risk of long Covid [76]. In addition, people who took
regular probiotics had a 14% lower risk of symptomatic Covid
[77]. Many clinical trials are underway globally examining the role
of pro and prebiotics in both prevention and treatment of Covid
and some have reported benets [1,8,57,78-82]. Considering this
background of evidence, this study aimed to examine whether
their administration could reduce the severity and longevity of
symptomatic Covid infection, particularly those with ongoing
symptom, via their gut health promoting, immunomodulatory and
anti-inammatory and direct actions.

Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI: 10.29011/2577-1515.100182
3Volume 5; Issue 01
Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
Methods
This experimental trial was conducted at Bedford Hospital,
part of the Addenbrooke’s Hospital Cambridge University Trust
Network. All participants (n=126, 70 male, 56 female) had one
or more symptoms related to their Covid infection at the time of
trial entry. Participants were recruited between May 2020 and May
2021, approached either at the local post Covid clinic, or from the
daily Covid ward round or had contacted the trials unit themselves
directly after hearing about the study via word of mouth. For this
analysis, we only included participants who were given a capsule
containing a 5 species Lactobacillus probiotic blend with inulin
prebiotic derived from chicory for at least one month. The daily
dose (from 2 capsules) was 200 mg of Inulin and 10 Billion Colony
Forming Units (CFU’s) of Lactobacillus plantarum (Lp90),
Lactobacillus rhamnosus (LRa05), Lactobacillus bulgaricus
(LB42), Lactococcus lactis (La61), Lactobacillus paracasei
(LC86).
People were excluded if they had known sensitivities and
allergies to the investigational foods, were immune-suppressed or
were too ill to take oral capsules. The average age 53 years (range
16-82). Eighty-three (66%) were smokers, 42 (34%) non-smokers.
The average BMI was 28.7 Kg/m2 , 47 (37.3%) were normal
weight (BMI 18-<25 Kg/m2 ), 79 (62.7%) were in the overweight
or obese range (BMI >25 Kg/m2) (30% overweight, 32.7% obese).
The average time from Covid diagnosis to trial entry was
108 days (range 2-467). The group was analysed as a whole and
then subdivided into 40 (32%) in the Early Phase (EP) of infection
(within 30 days of diagnosis) and 86 (68%) in a Chronic Phase
(CP) of persistent symptoms (>30 days from diagnosis). Of the
individuals in this chronic phase Covid group, the average time
from diagnosis and trial entry was 120 days and for the individuals
in the early phase this was 10 days.
Symptoms were recorded at trial entry and at 30 days 3
using validated questionnaires (The Cough Symptom Score, the
Subjective Well-Being questionnaire and the Chandler fatigue
questionnaire) [83-85]. All other symptoms were recorded using
the NCI Common Toxicity Checklist.
Manufacture
The food supplement was made specically for this trial by
Park-acre, Lincoln, DN21 5TJ and The Oxford Health Company
Ltd, Oxfordshire, OX26 5AH. Certied to conform to Good
Manufacturing Practice (GMP-FSSC 22000, ISO 22000), UK
and International food production laws [www.tohc.co.uk]. They
are also certied organic by the Organic Food Federation. There
in-house Research and Development department, for each batch
tested for contamination with yeast, mould, E. coli, Salmonella.
They measured lead, arsenic, cadmium, mercury and pesticides
then excluded batches, which did not abide by international
threshold guidance and law. A unit of the supplements are securely
stored by the Trust Secretary and can be sent to any regulatory
body at their request in the future.
Statistical analysis
The primary end points for this analysis were mean cough,
fatigue and subjective well-being symptoms scores on one day one
and day 30, for the whole cohort and then split into early phase
and chronic phase groups. Statistical analysis was performed using
IBM SPSS Statistics (IBM Corp., Amonk, NY, United States).
All dependent variables were checked for normal distribution
using Quantile-Quantile (Q-Q) Plots and were deemed plausible
in all instances. All data was presented as mean ± SD with 95%
condence intervals (95%CI). A dependent paired sample t-test
was used to assess the mean differences in cough, subjective
wellbeing and fatigue scores at day 1 compared with day 30. The
two-tailed alpha level was set as P<0.05. Cohen’s d effect size
were used to show the magnitude of change for each signicant
difference using the following thresholds; 0.2-0.49 small, 0.5-0.79
moderate, >0.8 large).
A predetermined subgroup determined which participants
had the most benet to the intervention by comparing the change
in mean symptoms scores from baseline to day 30 between male
versus (vs) female; normal weight versus overweight or obese; <60
years vs >60 years; ethnic group (White British vs other); Exercise
levels (<3 hours a week v >3 hours a week); hospitalised vs not;
history of bowel symptoms vs not, gastrointestinal symptoms at
baseline vs not. An independent t-test was used to determine the
differences in scores between normally distributed subgroups.
A between groups one way analysis of variance (ANOVA) were
used to determine differences for all other sub-group analysis.
Assumptions of both tests were checked via the homogeneity of
variance, which were not violated for any variables. In the instance
of a signicant main effect, a Bonferroni pairwise comparison was
used to locate signicant differences. The two-tailed alpha level
was set as p<0.05.
Results
Formal symptoms scores
Table 1 summarises the changes in formal cough, fatigue
and well-being scores over the 30 days intervention for the whole
cohort and separately for the patients who received probiotics in
the acute and chronic phases of Covid (Table. 2).

Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI: 10.29011/2577-1515.100182
4Volume 5; Issue 01
Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
Symptom Score Mean & SD
(Day 1 vs 30)
Difference
(Day 1 vs 30) 95%CI p value
Cough
1.25 ± 1.99
vs
0.42 ± 1.01
0.83 ± 1.74 0.52 to 1.14 p<0.001
Fatigue
21.37 ± 5.59
vs
16.57 ± 6.80
4.74 ± 6.85 3.58 to 6.01 p<0.001
Subjective wellbeing
24.05 ± 8.47
vs
28.38 ± 6.95
4.11 ± 9.62 5.98 to -2.67 p<0.001
Table 1: Changes in symptoms from day 1 to 30 days (all patients, n=126).
Cough scores signicantly decreased over the 30 days from a mean of 1.25 (± 1.99) to 0.42 (± 1.01) (t124 = 5.331, p<0.001; 95%CI:
0.52 to 1.14, d=0.48). Fatigue scores were signicantly improved from a mean of 21.37 (± 5.59) to 16.57 (± 6.80), (t118=5.178, P<0.001;
95%CI: 3.58 to 6.01, d=1.36) by a large magnitude (d=1.36)). Subjective wellbeing demonstrated a signicant improvement by a large
magnitude from a mean of 24.05 (± 8.47) to 28.38 (± 6.95) (t124=7.823, p<0.001; 95%CI: -5.98 to -2.67, d=1.10).
Symptom Scores Mean & SD
(Day 1 vs 30)
Difference
(Day 1 vs 30) 95% CI p value
Early Covid cohort (n=40)
(symptoms developed within one month of trial entry (mean 14 days)
Cough
1.84 ± 2.33
vs
0.61 ± 1.27
1.24 ± 2.33 0.42 to 2.07 p=0.004
Fatigue
20.19 ± 5.69
vs
14.44 ± 4.53
4.70 ± 6.90 2.88 to 8.61 p<0.001
Subjective wellbeing
24.45 ± 9.69
vs
30.94 ± 6.06
6.48 ± 10.39 10.17 to -2.8 p=0.001
Chronic Covid cohort (n=96)
Symptoms persistent > 1 month from trial entry (Mean=120 days)
Cough score
1.03 ± 1.82
vs
0.35 ± 0.89
0.67 ± 1.45 0.38 to 0.98 P<0.001
Fatigue score
21.66 ± 5.55
vs
17.18 ± 7.20
4.70 ± 6.85 3.13 to 5.82 P<0.001
Subjective wellbeing
23.99 ± 8.04
vs
27.51 ± 7.03
3.23 ± 9.20 5.33 to -.70 p<0.001
*Early Covid: symptoms within 1 month of trial entry; + Chronic Covid: Participants with symptoms for >1 month prior to trial entry
Table 2: Changes in Covid symptoms from day 1 to 30 days split into early and chronic cohorts.

Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI: 10.29011/2577-1515.100182
5Volume 5; Issue 01
Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
Both fatigue and subjective wellbeing scores were signicantly improved in the acute (fatigue: t39=4.120, P<0.001, 95%: 2.88 to
8.61, d=1.8; Subjective wellbeing: t39=3.585, P=0.001, 95%: 2.80 to 10.17, d=1.6) and chronic (fatigue: t95=6.618, P<0.001, 95%: 3.13
to 5.82, d=1.3; Subjective wellbeing: t95=3.840, P<0.001, 95%: 0.70 to 5.33, d=0.9) phase groups by a large magnitude. Furthermore,
cough scores were signicantly improved by a moderate effect size in the acute (t39=3.060, P=0.004, 95%: 0.42 to 2.07, d=0.6) phase
group and by a small magnitude in the chronic (t95=4.472, P<0.001, 95%: 0.38 to 0.98, d=0.4) phase group.
Self-reported symptoms
The top 7 self-reported symptoms were fatigue, shortness of breath, pains, altered sense of smell, bowels symptoms, cough and headache
(Table 3). Table 4 (excluding cough and fatigue) summarised how these self-reported symptoms changed over the 30 days of the
intervention with bowel symptoms improving the most.
Symptom Number (%) Symptom Number (%)
Fatigue 117 (92%) Sore throat 7 (6%)
Breathlessness 53 (42%) Anxiety or depression 7 (6%)
Joint, muscle or chest pains 43 (34%) Altered hearing or vision 6 (5%)
Bowel symptoms, nausea 31 (25%) Increased BP 6 (5%)
Cough 31 (25%) Peripheral neuropathy 5 (4%)
Altered sense of smell 31 (25%) Dizziness 5 (4%)
Headache 24 (19%) Increased perspiration 4 (3%)
Muscle weakness 22 (17%) Sneezing 4 (3%)
Fever / chills 18 (14%) New onset asthma / asthma are 4 (3%)
Poor appetite, nausea 14 (11%) Altered voice / hoarseness 3 (2%)
Insomnia 10 (8%) Hyperesthesia 3 (2%)
Heart palpitations 8 (6%) Urinary problems 3 (2%)
Brain fog 8 (6%) Weight loss 3 (2%)
Skin rash / Covid toes 8 (6%) Period problems 2 (1%)
Table 3: Self-reported symptoms at baseline (any grade of severity).
Symptoms Number (%) Symptom Number (%)
Bowel symptoms 25 of 31 (82%) Headache 3 of 24 (13%)
Sleep pattern 8 of 10 (80%) Skin oiliness 1 of 6 (16%)
Brain fog or headache 3 of 8 (38%) Asthma relief 1 of 4 (25%)
Breathlessness 11 of 53 (21%) Sneezing 1 of 4 (25%)
Joint or chest pains 7 of 43 (16%) Decreased palpitations 1 of 8 (12%)
Table 4: Percentage of self-reported symptoms improving at 30 days other than cough and fatigue (reported above).

Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI: 10.29011/2577-1515.100182
6Volume 5; Issue 01
Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
Subgroup analysis
Subgroups were predetermined to evaluate whether some individuals had a greater or lesser benet from the intervention. These
subgroups included gender, Body Mass Index (BMI), age, ethnic group, exercise levels, whether hospitalised, whether they had a
history of GI symptoms and whether they had new GI symptoms at trial entry. Although there was no difference in relative benet
between different ethnic groups or BMI levels, it appeared that males, those <60 years, those exercising more than 3 hours a week, those
previously hospitalised, no prior indigestion, new or worse GI symptoms at trial entry had a statistically greater benet for one or more
measurable outcomes (Table 5).
Symptom scores Mean score change Day 1 to 30
SD (number)
Difference
(95% CI) P value
Gender
Male (70) vs Female (56)
Cough 1.1 ± 2.0 vs 0.5 ± 1.2 0.6 (0.1 to 1.6) p=0.04
Fatigue 6.4 ± 7.2 vs 3.2 ± 6.2 3.2 (-0.6 to 0.5) p=0.01
Subjective wellbeing 5.3 ± 10.6 vs 2.6 ± 8.0 2.7 (0.6 to 5.6) p=0.10
Age
<60 years (89) vs >60 years
(37)
Cough 0.6 ± 1.8 vs 0.9 ± 1.7 0.3 (0.9 to 0.4) p=0.46
Fatigue 1.6 ± 5.3 vs 6.4 ± 7.0 4.8 (7.2 to 2.5) p<0.001
Subjective wellbeing 1.4 ± 9.8 vs 5.2 ± 9.4 3.8 (0.2 to 7.5) p=0.04
Ethnic group
White British (92) v other (34)
Cough 0.8 ± 1.8 vs 0.7 ± 1.7 0.1 (-0.8 to 0.5) p=0.64
Fatigue 4.9 ± 7.1 vs 5.3 ± 6.5 0.4-2.4 to 3.3 p=0.74
Subjective wellbeing 4.2 ± 10.3 vs 3.8 ± 7.5 0.4 (-3.4 to 4.2) p=0.82
BMI
Normal (46) vs OW and O (80)
Cough 0.8 ± 1.5 vs 0.7 ± 1.9 0.1 (-0.8 ± 1.5) p=1.00
Fatigue 2.7 ± 10.1 vs 4.7 ± 9.3 2 (2.6 to 4.7) p=1.00
Subjective wellbeing -4.2 ± 10.3 vs - 3.8 ± 7.5 0.4 (-2 to 4) p=0.13
Hospitalised
Yes (79) vs No (47)

Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI: 10.29011/2577-1515.100182
7Volume 5; Issue 01
Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
Cough 0.9 ± 1.6 vs 0.7 ± 1.9 0.2 (-0.5 to 0.7) p=0.77
Fatigue 6.1 ± 7.4. vs 2.9 ± 5.5 3.2 (0.9 to 5.6) p<0.01
Subjective wellbeing 3.5 ± 9.0 vs 5.1 ± 10.5 1.6 (-2.0 to 5) p=0.39
Prior indigestion
Yes (113) vs No (13)
Cough 0.8 ± 1.7 vs 1.0 ± 2.1 0.2 (0.8-1.2) p=0.70
Fatigue 9.4 ± 7.9 vs 4.4 ± 6.6 5 (0.1-11.1) p<0.01
Subjective wellbeing 9.1 ± 11.5 vs 3.5 ± 9.2 5.6 (8.9-1.1) p=0.04
New GI symptoms at baseline
Yes (41) vs No (85)
Cough 0.7 ± 1.9 vs 0.8 ± 1.7 0.1 (-0.5 to 0.8) p=0.59
Fatigue 5.4 ± 7.0 vs 4.2 ± 6.8 1.2 (-1.5 to 3.8) p=0.01
Subjective wellbeing 2.7 ± 10.1 vs 4.7 ± 9.3 2 (-5.6 to 1.6) p=0.274
Exercise
3 >hrs/wk (93) vs <3hrs/wk (33)
Cough 0.5 ± 1.3 vs 1.6 ± 2.4 1.1 (0.2-1.9) p=0.02
Fatigue 4.1 ± 6.4 vs 7.6 ± 7.8 3.5 (0.3-6.7) p=0.03
Subjective wellbeing 2.7 ± 6.4 vs 8.0 ± 11.4 5.3 (-9.7to-0.9) p=0.02
Table 5: Subgroup analysis highlighting who got the greatest benet from the intervention.
Safety and adverse events
The assessment of safety was based on the frequency of adverse events reported by the investigator in the Case Report File. The
level of adverse events attributable to the probiotics were very low (Table 6) with only two (1.5%) patients reported mild increased
bloating and diarrhoea. At trial entry, it was also observed that, of the participants who were overweight or obese, 15% indicated they
never exercised as opposed to 2% in the normal weight group. In the overweight or obese group, 15% ate meat less than 3 times a week
compared to 28% in the normal weight group. Likewise, 15% of the overweight or obese participants added more than 2 spoons of sugar
in their tea or coffee as opposed to 4% in the normal weight group.
Adverse event Number (Percentage of 126) NCI toxicity (Severity)
Increased bloating 2 (1.5%) 1 (Mild)
Increased diarrhea 2 (1.5%) 1 (Mild)
Increased indigestion 2 (1.5%) 1 (Mild)
Table 6: Adverse events attributable to nutritional intervention.

Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI: 10.29011/2577-1515.100182
8Volume 5; Issue 01
Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
Discussion
This study highlights the wide variety of symptoms patients
suffer following a Covid-19 infection and draws attention to the
high prominence of those of Gastro-Intestinal (GI) origin. Self-
reported GI symptoms of indigestion, bloating, nausea, diarrhoea
and constipation were reported to have developed or increased from
their usual level in over a quarter of patients at baseline. Previous
publications have highlighted that patients with GI symptoms at
presentation had worse non-GI symptoms, particularly fatigue,
during their Covid episode, and had a greater risk of developing
chronic on going symptoms [4,5,7,8]. GI symptoms have been
attributed to direct viral growth within the gut mucosa causing
inammation and dysbiosis in the gut bacterial ora [4,5,7,8,80].
This intervention, which aimed to improve gut health with
a combination of lactobacillus probiotics and inulin prebiotics,
demonstrated a clear improvement in fatigue, cough, subjective
wellbeing and self-reported GI symptoms after their initiation.
For patients within the early phase of an infection (less than 30
days), this result was largely expected as most patients improve
within a month of an acute infection, although the same cannot
with said for participants with chronic persistent Covid-related
symptoms [78,79]. In this cohort, participants had ongoing
symptoms for an average of 120 days months pre-entry and
therefore, improvement in symptoms seen within 30 days of the
intervention, would unlikely to have happened spontaneously. This
improvement was considered clinically relevant and welcomed by
participants. This nding supports similar benets from probiotic
interventions, reported in patients, mainly with other respiratory
tract viral infections, but more recently in patient with Covid
[1,4,8,54,73,76,77,81]. Furthermore, it supports ndings from the
Kings App study, which established a link between people who
took probiotics and a lower risk of Covid [76].
In terms of a subgroup differences, patients admitted to
hospital had a greater improvement after this intervention compared
to non-hospitalised patients. A possible explanation for this is that,
gut dysbiosis is aggravated by treatments such as dexamethasone
and antibiotics, often administered to patients during their hospital
Covid management, so we suggest that an intervention to improve
gut health has an even greater impact on these patients [86-88].
Likewise, benet from this intervention was greater in the older
participants and those who exercised less, also factors known to
be linked to less favourable gut microoral prole [47,89]. Males
had statistically signicantly better benet to the intervention than
females, which is a clinically relevant factor as it has previously
been reported that males have worse outcomes after Covid [88].
Our data, therefore, adds weight to the discussion that underlying
variance in gut microbiota could be an explanation for this gender
difference [90].
The mechanism of action of the probiotics, for non-GI
symptoms, was not addressed in this study but the improvement
in respiratory symptoms may be explained by improvement in the
gut-lung axis highlighted in the introduction [13-17]. The cause of
fatigue, common during a viral infection and particularly Covid,
is not certain. Some postulate there is an evolutionary advantage
for fatigue within the innate immune related response as it reduces
movement and interaction with other people and hence spread of the
virus [91]. It is well known that poor gut health has a link to chronic
fatigue [85,92-94]. Previous interventions with lactobacillus
supplements reduced fatigue related behaviour in laboratory
animals [63]. In humans, there have been reported improvements
in fatigue and memory following probiotic interventions which
also demonstrated reductions in systemic inammatory cytokines
and improvements in gut integrity [63,93,94]. Some studies
have shown a microbial-neuroendocrine relationship between
certain dysbiotic ora species and the resultant adverse change
in hormones and neurotransmitters such as acetylcholine and
Gamma-Amino Butyrate (GABA), serotonin and dopamine and
that administration of lactobacillus probiotics helped reverse these
changes [64,92-96]. Although these are all a possible mechanisms,
further research is required to establish whether these biochemical
changes are responsible for the profound fatigue in those with long
Covid.
Going forward, these data suggests that, in terms of Covid,
greater emphasis should be placed on eating behaviour, nutritional
factors and exercise which improve gut biodiversity. Various studies
have shown these factors include stopping smoking, reducing
processed sugar, exercising more, eating more live probiotic
bacteria within yogurt, ker, sauerkraut and kimchi, eating
more fermentable soluble bres such as inulin, oligosaccharides
and beta-glucans found in chicory, artichoke, grains, beans and
mushrooms and prebiotic polyphenols found in nuts, onions,
fruit pomegranate and herbs [22,52,53,87]. In addition, this study
suggest that concentrating elements of these foods into capsules has
a benecial role. Nutritional supplement are certainly a convenient
way to boost probiotic and prebiotic intake throughout the day.
Many laboratory and some human studies that show probiotic
capsules improve mirocrooral biodiversity, improve immune
efciency, correct GI symptoms and modify a range of chronic
diseases [21,28,34-36]. Other intervention trials have shown they
can reduce the incidence of upper respiratory tract viral and u like
infections [38-44]. We believe, our data is one of the rst to report
the potential benet for patients with symptoms post Covid.
In terms of safety, thousands of studies, have reported a high
safety record among millions of healthy people who have consumed
probiotic capsules for years, particularly the lactobacillus varieties
[64,97-103]. More relevant to this study, the intake of lactobacillus
probiotics has been shown to be particularly safe and benecial

Citation: Thomas R, Aldous J, Forsyth R, Chater A, Williams M (2021) The Inuence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the
Duration and Severity of Symptoms among Individuals with Covid-19. Infect Dis Diag Treat 5: 182. DOI: 10.29011/2577-1515.100182
9Volume 5; Issue 01
Infect Dis Diag Treat, an open access journal
ISSN: 2577-1515
among patients with several different medical condition including
those on chemotherapy, those with irritable bowel syndrome and
premature infants as well as elderly and even immunocompromised
patients, hence a rationale for their inclusion in this study [102-
104]. We add to this data by reporting this lactobacillus blend was
safe in patients who had ongoing symptoms following a Covid
infection. Only two patients discontinued their capsules because
of an increase in bloating although it was not certain whether this
was related to the intervention.
Data from this study would have been more robust if a
randomised design was used, however, despite the high number of
Covid cases in our hospital at the start of the trial, it became clear
that participants would buy their own probiotics, over the counter,
negating the any comparative data. Considering these factors and
following feedback from patients, the trials committee decided to
provide the probiotic to all participants, with the design limitations
acknowledged.
Conclusion
This study highlights the wide range of symptoms people
suffer following a Covid infection, in particular, those related to
GI tract. As it is known that patients with Covid with GI symptoms
and other factors linked to gut dysbiosis have more severe and more
persistent of symptoms, it would be wise to encourage lifestyle and
nutritional factors, which improve the gut microbiome. In addition,
this study strongly suggests that this specic probiotic supplement,
enhances recovery from Covid especially for individuals who
have symptoms or conditions suggestive of poor gut health. This
blend of pro and prebiotics was safe and well tolerated, is now
freely available as an over the counter supplement known as
yourgutplus+ but it must be noted that it is classied as a food so
cannot be licenced or prescribed by medical practitioners. Further
research on this trial cohort will evaluate whether the addition of
a phytochemical rich whole food supplement will further enhance
the benets of this intervention, which will be reported separately.
Going forward, our research group are now designing a study to
evaluate whether yourgutplus+ could also enhance antibody titres
post Covid vaccination.
Acknowledgements
The interventional capsules, subsequently known as
yourgutplus+, were designed by the scientic committee
specically for this study, made by The Oxford Health Company
Ltd, and donated free by Keep-healthy Ltd, Isle of Man who we
would like to thank, as without their generous support this study
would have not been possible. We are grateful to the post Covid
clinic, Bedford Hospital for their vital help in recruiting patients.
Declaration of Interest
This was a non-commercial trial and no direct funding has
been received from external organisations although the probiotics
was supplied free of charge to the trials unit as mentioned above.
The research team involved in the study were not being paid to
recruit patients into the study, had no other nancial incentives
and have no connection with the manufactures. There are no
intellectual patent issues on any of the investigational products as
these are freely available over-the-counter. Information generated
by the trial will be published in the public domain and the authors
have no other conict of interest.
Certication
This trial was approved by the Health Research Authority
(REC reference: 20/YH/0164), sponsored and approved
by Bedfordshire Hospitals NHS trust and its Research and
Development committee. The Medicines and Health Regulatory
Agency (MHRA) gave formally authority to proceed with the trial
as no medical products license is required for food products.
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