UNIVERSIDADE ESTADUAL PAULISTA

“JÚLIO DE MESQUITA FILHO”

Instituto de Ciência e Tecnologia

Campus de São José dos Campos

SYSTEMATIC REVIEW DOI: https://doi.org/10.4322/bds.2023.e3619

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Is the use of

Lactobacillus reuteri

probiotic eﬃcient as adjunctive

therapy in the treatment of periodontitis? A systematic review

O uso do probiótico

Lactobacillus reuteri

como terapia adjuvante no tratamento da periodontite é eﬁcaz? Uma revisão sistemática

Tainá da Silva TRICOLY

, Camila Lopes FERREIRA

, Victória Clara da Silva LIMA

, Andrea Carvalho de MARCO

,

Taciana Marco Ferraz CANEPPELE

, Maria Aparecida Neves JARDINI



1 - Universidade Estadual Paulista , Instituto de Ciência e Tecnologia, Departamento de Diagnóstico e Cirurgia, São José dos Campos, SP, Brazil.

How to cite: Tricoly TS, Ferreira CL, Lima VCS, Marco AC, Caneppele TMF, Jardini MAN. Is the use of

Lactobacillus reuteri

probiotic efcient as adjunctive therapy in the treatment of periodontitis? A systematic review. Braz Dent Sci. 2023;26(1):e3619.

https://doi.org/10.4322/bds.2023.e3619

ABSTRACT

Objective: This systematic review had the purpose to validate the probiotic

Lactobacillus reuteri

as adjuvant therapy

in the periodontal treatment of periodontitis, by the analysis of randomized controlled trial, controlled clinical trial,

and observational studies. Material and Methods: Search keys related to the subject were dened, and the following

databases were used as search strategies: MEDLINE via PubMed, Scopus, Web of Science, Cochrane Central Controlled

Trials Registry, and EMBASE. The data selection and study were performed by two independent evaluators: rst, they

selected the article by title and abstract and subsequently qualied according to the bias risk analysis. A narrative

synthesis has been performed based on the data obtained from the best-quality articles. After data extraction, their

heterogeneity was analyzed, and a meta-analysis was performed. Results: In general, the results of the meta-analysis

were positive for the use of probiotics as an adjuvant treatment. Considering the limitations of the comparisons between

the analyzed articles studied, the conclusion was that probiotics may provide supplementary benets to the treatment

of periodontitis, with improvement in bleeding on probing rates and probing depth.

KEYWORDS

Lactobacillus reuteri

; Periodontal diseases; Periodontitis; Probiotics; Systematic review.

RESUMO

Objetivo: Esta revisão sistemática teve como objetivo validar o uso do probiótico Lactobacillus reuteri como terapia

adjuvante no tratamento periodontal da periodontite, por meio da análise de ensaios clínicos randomizados,

ensaios clínicos controlados e estudos observacionais. Material e Métodos: Chaves de busca relacionadas ao

assunto foram denidas, e as seguintes bases de dados foram utilizadas como estratégias de busca: MEDLINE via

PubMed, Scopus, Web of Science, Cochrane Central Controlled Trials Registry e EMBASE. A seleção dos dados

e o estudo foram realizados por dois avaliadores independentes: primeiro, selecionaram o artigo pelo título e

resumo e posteriormente qualicaram de acordo com a análise de risco de viés. Uma síntese narrativa foi realizada

com base nos dados obtidos dos artigos de melhor qualidade. Após a extração dos dados, sua heterogeneidade

foi analisada e uma meta-análise foi realizada. Resultados: Em geral, os resultados da meta-análise foram

positivos para o uso de probióticos como tratamento adjuvante. Considerando as limitações das comparações

entre os artigos analisados estudados, concluiu-se que os probióticos podem trazer benefícios complementares ao

tratamento da periodontite, com melhora nas taxas de sangramento à sondagem e na profundidade de sondagem.

PALAVRAS-CHAVE

Lactobacillus reuteri

; Doença periodontal; Periodontite; Probióticos; Revisão sistemática.

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

INTRODUCTION

Periodontal disease is a chronic microbial

infectious disease, defined as enduring

inflammation and destruction of connective

tissue and alveolar bone [1]. Nowadays, research

scientists have evaluated distinct factors that must

be examined in the analysis of periodontal disease,

as well as the presence of pathogenic bacteria, the

susceptibility of the host, and the reduction or

absence of benecial microorganisms [2-4].

Periodontitis is a relevant medical issue

since its signicant prevalence can result in tooth

loss and dysfunction, chewing problems, and

unsatisfactory aesthetics. In addition, it can be

associated with social inequality and a decrease

in the patient’s quality of life. Periodontitis is

responsible for a vast amount of edentulism and

masticatory dysfunction, resulting in expensive

dental care and adverse impacts on overall

health [5]. Although gingivitis and periodontitis

are originated and maintained by the microbial

biofilm of dental plaque, host genetic and

environmental aspects can also affect the disease

progression [6].

The dental biofilm has a polymicrobial

nature and over 700 species of bacteria are part

of the oral microenvironment [7]. This resident

microora lives in symbiosis with the host and

contributes directly and indirectly to its natural

physiology, nutrition, and defense systems [8].

The rst approach for periodontitis is a non-

surgical treatment, which consists of scaling and

root planning in association with oral hygiene

instruction [9]. Mechanical therapies aim to improve

clinical conditions, reducing the microbial load,

either by physical removal or by disorganization

of the subgingival biolm [10]. Despite mechanical

debridement has been considered the gold standard

for the treatment of periodontitis, it’s a technique

that provides some obstacles, such as difcult access

in cases of deep pockets, distortions in the root

surface, as well as furcation areas [11], leading to

the persistence of the disease process.

In order to achieve better root surface

decontamination, different adjuvant treatments

have been suggested, such as antibiotics [12],

antiseptics [13], or microbial photodynamic

therapy [14].

In this scenario, probiotics use were

considered for the treatment of gingival and

periodontal conditions [15,16]. The mechanisms

related to the use of probiotics are the host’s

immunoinflammatory modulation [17], the

attenuation of periodontal pathogen-induced

interleukins expression in epithelial oral

cells [18], and the reduction of pro-inammatory

cytokines [19].

The Food and Agriculture Organization

(FAO) and the World Health Organization

(WHO) dene probiotics as “live microorganisms

that, when present in acceptable amounts,

provide health advantage to the host” [20]. Most

parts of microorganisms used as probiotics are

bacteria of the genus

Lactobacillus

Enterococcus

Bacillus,

and

Bidobacterium

[21].

Lactobacillus reuteri

is a lactic-acid,

gram-positive, and facultative anaerobe

microorganism [22] found in the gastrointestinal

and urogenital tracts of humans, in breast

milk, and in the gastrointestinal tract of some

animals, such as rats, chickens, and pigs [23].

Immunomodulation of the host’s intestinal

microbiota, suppression of pro-inflammatory

cytokines [22,24], histamine production [25], and

increase in vitamin B12 synthesis [26] are some

examples of favorable consequences related to the

use of this probiotic. Studies have also elucidated

the important benefits of

L. reuteri

for bone

health, indicating reduced osteoclastogenesis, an

increase in bone mineral density, which leads to a

decrease in the risk of fractures [27], an increase

in circulation of vitamin D, and, consequently,

higher absorption of calcium by the organism [28].

Lactobacillus reuteri

is a part of the oral

microbiota in humans, and it has antibacterial

action by transforming glycerol into reuterin

(3-hydroxypropionaldehyde (3-HP),

a substance that has a broad antimicrobial

spectrum [29], inducing oxidative stress in

pathogenic microorganisms [30]. In addition, this

probiotic has shown an effect on the maintenance

of healthy microbial flora, by preventing

the excessive growth of other pathological

microorganisms [31].

Different studies have analysed the results of

probiotics in the treatment of periodontal diseases

in humans [19,29,32-40]. For most of these

studies, the use of the probiotic demonstrated a

reduction in bleeding on probing (BoP), plaque

index (PI), gingival index (GI), probing depth

(PD) and number of mandatory anaerobes

microorganisms.

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

Given the results of studies found in the

literature, the use of probiotic therapy adjuvant

to the treatment of periodontal disease in humans

is developing as a probable treatment option.

This present systematic study may contribute to

future studies, allowing new clinical trials design,

identication and correction of methodology gaps

and determine clinical guidelines on this subject.

MATERIAL AND METHODS

Protocol and registration

This systematic study followed the

international parameters of transparency in

Systematic Review and PRISMA Statement

Meta-Analysis [39] and was registered in the

PROSPERO base (https://www.crd.york.ac.uk/

prospero/) n0 CRD42021236186.

Eligibility criteria

The selected studies for analysis followed

the PICO criteria:

Population: Patients with periodontal

disease

Intervention: Patients who received adjuvant

periodontal treatment with the probiotic

Lactobacillus reuteri

Comparison: Patients who received non-

surgical periodontal treatment (scaling and root

planing - SRP) exclusively or in combination

with placebo

Outcome: Improvement in the main clinical

periodontal parameters (PD and BoP)

Inclusion criteria

1) Studies published in English

2) Controlled and randomized clinical trials

(RCT)

3) Studies that evaluated the treatment of

patients with periodontitis comparing SRP

+ probiotic

Lactobacillus reuteri

versus SRP

+ placebo or SRP only

4) Results reported in terms of probing pocket

depth

Exclusion criteria

1) If patients with systemic disease were

included

2) If they were duplicated or secondary study

Search strategy

In this present study, randomized

clinical trials, controlled clinical trials and

observational studies were investigated. To be

the most comprehensive as possible, there was

no restriction regarding the time after treatment

or the year of publication. The authors performed

an examination of the MEDLINE collection

of data via PubMed, Scopus, Web of Science,

Cochrane Central Register of Controlled Trials,

and EMBASE, for articles published until April

2020. The search was updated on January 2023.

All studies were identied by the inclusion criteria

and there was no need for additional contact with

authors to identify other information.

Considering the components of the questions,

terms and synonyms that could enhance the

accuracy of the study were found. Initially,

the word in Portuguese was inserted in the

Health Sciences Descriptors (DeCS) and the

descriptor in English was obtained. The terms

found were associated to the terms “AND”,

“OR” or “NOT” to constitute the following

search strategy: “Probiotics and Periodontal

Disease” and Periodontal Disease, Probiotics”

according to MeSH and, the uniterms will be:

(“probiotics”[MeSH Terms] OR “probiotics”[All

Fields]) AND (“periodontal diseases”[MeSH

Terms] OR (“periodontal”[All Fields] AND

“diseases”[All Fields]) OR “periodontal

diseases”[All Fields] OR (“periodontal”[All Fields]

AND “disease”[All Fields]) OR (“periodontal

disease”[All Fields])).

Data extraction

Two reviewers were responsible for searching

the scientic articles (an undergraduate student

and a Ph.D. candidate), previously calibrated

by a third reviewer (Principal Investigator).

The inter-examiner test (Kappa) was applied to

assess agreement (twice) of the selected titles and

abstracts obtaining a result of 0,89. At each stage

there was a meeting between the three reviewers

to analyse discrepancies, that were resolved by

the third reviewer. All titles and abstracts of

eligible papers were assessed by the “Covidence”

program and thoroughly analysed.

The details for systematic review selection

are shown in Figure 1, as recommended in the

literature [42].

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

Data item

Data extracted from each study were grouped

in: 1) Author; 2) Publication year; 3) Type of

study; 4) Number of patients; 5) Age; 6) Total

dose (daily dose multiplied by the consumption

time in colony forming units [CFU]); 7) Frequency

and duration of consumption; 8) Follow-up time.

Risk of bias in individual studies

The character of the involved studies was

evaluated using the Cochrane Library Risk Tool

for Randomized Clinical Trials (RoB 2) (updated

on March 15th, 2019), by a calibrated examiner

(MJ) and by a second examiner (CF) for ensure

agreement on the scoring system. The studies

were divided in low, moderate, high, or imprecise

risk of bias, which were based on ve domains:

(a) resulting from the randomization process; (b)

due to deviations from the proposed intervention;

results; (e) in the selection of results. (Figure 2)

Research and evaluation results

After search, 12 articles were selected (Table 1).

During data extraction, the different

treatment protocols were grouped by similarities,

and a meta-analysis was performed for the two

outcomes mentioned.

Meta analysis

The data was analysed by the Studio R

software (version 3.4.4), using the R statistical

language. For the analysed outcomes (PD and

BoP), the results were presented as difference in

means (MD), with a condence interval of 95%.

The Cochran Q test was used to evaluate

the statistical heterogeneity of the treatment

results, associated with the I

inconsistency

test, where gures above 50% were treated as

indicative of signicant heterogeneity. In case

of signicant clinical heterogeneity (I

> 50%),

subgroup analysis was used to plot the results.

Subgroup analysis are secondary analyses, in

which studies were divided into groups according

to common characteristics and the analysed

outcomes were performed to determine whether

any signicant treatment effects occur according

to this characteristic. Subgroup analysis of

included studies were performed for follow-up

time characteristics.

For the meta-analysis of PD and BoP

outcomes, the articles were organized according

to follow-up time, 3 and 6 months.

Figure 1 - PRISMA ﬂowchart. From: Pageetal. [41]. (*Consider, if feasible to do so, reporting the number of records identiﬁed from each

database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how

many records were excluded by a human and how many were excluded by automation tools.)

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

Table I - General characteristics of included studies

Author Year Study design Sample Age

Vehicle full

dose

Frequency Follow up

Grusovinetal. [39] 2019

Pilot study,

double blind and

randomized

20 patients 31-70 years 168 tablets Twice a day

3, 6, 9 and 12

months

Ikrametal. [43] 2018

Clinical trial,

double blind and

randomized

30 patients

Olden than 30

years

168 tablets Twice a day 6 and 12 weeks

Ikrametal. [44] 2019

Clinical trial,

double blind and

randomized

28 patients

Older than 30

years

- Once a day 6 and 12 weeks

Inceetal. [45] 2015

Clinical trial,

double blind and

randomized

30 patients 35-50 years 42 tablets Twice a day

Days 0, 21, 90,

180 and 360

Pelekosetal. [46] 2019

Clinical trial,

double blind and

randomized

59 patients

Older than 18

years

56 tablets Twice a day

Days 0, 90 and

180

Pelekosetal. [47] 2020

Clinical trial,

double blind and

randomized

40 patients - 56 tablets Twice a day

Days 90 and

180

Szkaradkiewiczetal. [48] 2014 - 38 patients 31-46 years 28 pills Twice a day

Two weeks

after pills

administration

Tekceetal. [49] 2015

Clinical trial and

randomized

40 patients 35-50 years 42 tablets Twice a day

Days 21, 90,

180 and 360

Teughelsetal. [37] 2013

Clinical trial and

randomized

30 patients

Older than 35

years

168 tablets Twice a day

3, 6, 9 and 12

weeks

Vicarioetal. [36] 2013

Clinical trial,

double blind and

randomized

19 patients

Older than 18

years

30 tablets Once a day After 30 days

Vivekanandaetal. [35] 2010

Clinical trial,

double blind and

randomized

30 patients 34-50 years 42 tablets Twice a day Days 0 and 42

Vohraetal. [50] 2019

Clinical trial,

double blind and

randomized

127 patients 50 years 42 tablets Twice a day 3 and 6 months

Figure 2 - Traﬃc light plots.

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

STUDIES DESCRIPTION

In a double-blind clinical trial, Ikram et al. [43]

gathered thirty participants diagnosed with chronic

periodontitis who underwent SRP. Half of the

patients received

L. reuteri

for 3 months, and the

other half received amoxicillin and metronidazole

for 7 days. The study concluded that there was a

similar improvement in both groups, indicating

that adjuvant probiotic agents showed similar

efcacy to therapeutic agents. In a second double-

blind clinical trial, Ikram et al. [44] continued their

study involving the use of

L. reuteri

, the new data

showed an improvement in the treatment when

using the probiotic, and they could conclude that

the probiotic approach is effective and a promising

alternative in adjuvant periodontal therapy. Also

with thirty patients, Ince et al. [45] concluded that

the analysed clinical parameters improved when

using the probiotic

reuteri,

in 2015.

Szkaradkiewicz et al. [48] recruited

38 patients and divided them into two groups.

For two weeks, one of the groups had probiotic

administration, while another one had placebo

administration. Subsequently, the control of the

patients was performed and, it was concluded

that there was a significant reduction in the

clinical indices of PI (plaque index), GI (gingival

index) and BI (bleeding index) in the test group.

As well, in 2012 Vicario et al. [36] concluded that

the administration of probiotics proved to be an

effective strategy for reducing inammation and

clinical symptoms of periodontitis.

Using the same approach of dividing into an

experimental and a control group, Tekce et al.

[49] analysed the microbiological and periodontal

parameters on administered

L. reuteri

in patient

with periodontitis, and concluded that the

probiotic helped to delay local recolonization

and improves clinical outcomes after periodontal

intervention. Teughels et al. [37] had also analyzed

microbiological parameters and their work showed

an important change in the amount of P. gingivalis

bacteria and an improvement in periodontal

parameters. In 2012, Vivekananda et al. [35]

recruited thirty patients and analyzeddetermined

parameters. They were able to conclude that

the administration of

L. reuteri

as an adjuvant

therapy inhibited bacterial plaque and had anti-

inammatory and antimicrobial effects.

In 2019, Vohra et al. [50] evaluating

127 patients concluded that the SRP treatment

was effective, regardless of the use of the

probiotic. In 2019, Grusovin et al. [39] obtained

positive results regarding PPD (pocket probing

depth), CAL (clinical attachment loss) and BoP

after administration of the probiotic

L.reuteri

Pelekos et al. [47] analysed possible changes

in the use of L.

reuteri

, specically in periodontal

pockets with PD >5mm in molars. According to

their study, the molar pockets were beneted from

the administration of the probiotic concluding

that new approaches related to the probiotic

dose, duration and administration way should be

taken. Previously, in 2019, Pelekos et al. [46] had

already studied L. reuteri in another clinical trial,

but the results were inconclusive and only showed

a trend towards successful treatment with the use

of probiotics. Likewise, correlating this study to

other from Grusovin et al. [39], Ikram et al. [44],

Pelekos [46,47] and Teughels et al. [37] had

showed a non-statistically signicant improvement

in the periodontal treatment using probiotics.

META ANALYSIS

DISCUSSION

This review considered 12 clinical studies

that evaluated the parameters of probing depth

and bleeding on probing after 3 and 6 months.

Initially, 526 results were found, but 290 were

duplicated. With the new number of 239 studies,

204 were excluded due to irrelevance, leaving

32 articles for analysis. After a deeper reading

of these 32 articles, 20 were excluded because

they did not t the parameters of this systematic

review, leaving 12 studies for analysis.

The following studies: Ikram et al. [43],

Pelekos et al. [46,47], Teughels et al. [37] and

Vivekananda et al. [35] also analysed clinical

attachment level indices. Ince et al. [45] and

Tekce et al. [49] analysed gingival recession

indices. As the analysed data were not presented

in all articles, only probing depth and bleeding

on probing data were considered in the meta-

analysis performed in this study.

All studies analysed the risk of bias and,

among them, 8 had low risk [35-37,44-46,49,50].

The study made by Grusovin et al. [39] had a

median risk of bias, and the last two studies,

Pelekos et al. [47] and Szkaradkiewicz et al. [48],

had a high risk of bias.

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

Figure 3 - Forest plot - 3-month follow-up on probing depth reduction (A) and decrease in bleeding on probing (B). (A) reduction in probing

depth and (B) decrease in bleeding on probing comparing scaling and root planing (SRP) and adjuvant probiotics versus scaling and root planing

(SRP). CI, conﬁdence interval; SD, standard deviation.

Figure 4 - Forest plot - 6-month follow-up on probing depth reduction (A) and decrease in bleeding on probing (B). (A) reduction in probing

depth and (B) decrease in bleeding on probing comparing scaling and root planing (SRP) and adjuvant probiotics versus scaling and root planing

(SRP). CI, conﬁdence interval; SD, standard deviation.

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

All the included studies had established

inclusion criteria, and the distribution of probiotics

was similar in all, ranging from 1 or 2 times a day

through lozenges. Only Szkaradkiewicz et al. [48]

used tablets methods and, Ikram et al. [43]

administered

L. reuteri

in sachet form, after

brushing.

At the 3-month follow-up for PD, 9 articles

were selected for the meta-analysis, resulting in

a favorable use of probiotics as adjuvant to SRP,

compared to groups that did not use probiotics

(-0.61, 95% CI [-1.08; -0.13], I

=95%; p = 0.01).

The articles by Vicario et al. [36], Vivekananda

et al. [35] and Szkaradkiewicz et al. [48] did not

analyse the data at 3 months and, therefore, were

not included in the meta-analysis. Among the

ones that were analysed, four showed signicant

improvement in probing depth with the use of

L.reuteri

[44,45,49,50].

Regarding the parameter bleeding on probing,

there was no meaningful difference in the use of

the probiotic

L.reuteri

in the 3 months results

(Figure 3). Virtually, all the articles analysed

obtained unfavourable or neutral results for the

use of probiotics (-6.16, 95% CI [-14.56; 2.24],

=97%; p < 0.01). Only two articles, among those

analysed, showed positive results for the use of

probiotics: Ince et al. [45] and Tekce et al. [49].

The follow-up evaluation after 6 months

showed that the number of articles that presented

these data were six for PD, and ve articles for

BoP (Figure 4). For PD, among those analysed,

most showed probing depth gain [45,46,49,50],

while Grusovin et al. [39] and Pelekos et al. [47]

showed no meaningful difference but had a

favourable result for the use of probiotics (-0.56,

95% CI [-0.83; -0.29], I

=80%; p < 0.01).

For BoP parameters, three of them did not show

an important difference for the use of probiotics,

these results were presented in Grusovin et al. [39],

Pelekos et al. [46] and Vohra et al. [50]. However,

in general, the analysis was positive regarding the

use of probiotic as an adjunctive therapy in the

treatment of periodontal disease (-5.57, 95% CI

[-9.70; -1.43], I

=85%; p < 0.01).

Probiotics are dietary supplements used to

preserve or promote health [51]. The probiotic

evaluated in the present review,

L.reuteri

, is a

bacterium capable of producing antimicrobial

molecules and remodelling the host’s commensal

microbiota [22]. It had also shown an effect against

periodontopathogens,

A. actinomycetemcomitans,

P.gingivalis., F. nucleatum, T. forsythia

, and other

oral pathogens, such as

S.mutans

[52].

Previous systematic reviews have shown

positive results regarding the use of

L.reuteri

in non-surgical periodontal therapy [53,54],

while the review by Akram et al. [55] analysed

its use in cases of gingivitis and, concluded that

there is no enough evidence on the reduction of

inammatory levels to support the use.

The primary limitation of this study is the

high heterogeneity found. This may be due to

the clinical and methodological diversities, such

as the differences between the methodologies

used for administering probiotics, the follow-up

time, the difference in the form of distribution

of probiotics, such as lozenges, sachets and

tablets, and the different amounts and nal dose

that each study uses, consequently each patient

receives. Thus, more randomized clinical studies

with similar methodologies are needed to analyse

the behaviour of L.reuteri as an adjuvant in non-

surgical periodontal treatment.

CONCLUSION

Considering the limitations of this present

study, it was concluded that probiotics may

provide supplementary benet to the treatment

of periodontitis, with improvement in bleeding

on probing rates and probing depth.

Author’s Contributions

TST, CLF, VCSL: Conceptualization,

Methodology. ACM, TMFC, MANJ: Formal

Analysis, Investigation, Resources, Writing –

Original Draft Preparation. TC, MANJ: Data

Curation. TST, CLF, VCSL, MANJ: Writing –

Original Draft Preparation. TST, CLF, VCSL,

ACM, TMFC, MANJ: Writing – Review & Editing,

Supervision. TST, TMFC, MANJ: Visualization.

Conict of Interest

The authors declare no conicts of interest.

Funding

Scholarship PIBIC Reitoria Edital 1/2020

-PIBIC.

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

Regulatory Statement

This study was conducted in accordance with

all the provisions of the local research subjects

oversight committee guideline.

REFERENCES

1. Caton JG, Armitage G, Berglundh T, Chapple ILC, Jepsen S,

Kornman KS,etal. A new classification scheme for periodontal

and peri-implant diseases and conditions: introduction and

key changes from the 1999 classification. J Clin Periodontol.

2018;45(Suppl 20):S1-8. http://dx.doi.org/10.1111/jcpe.12935.

PMid:29926489.

2. Slots J, Rams TE. New views on periodontal microbiota in special

patient categories. J Clin Periodontol. 1991;18(6):411-20. http://

dx.doi.org/10.1111/j.1600-051X.1991.tb02309.x. PMid:1890221.

3. Socransky SS, Haffajee AD. The bacterial etiology of

destructive periodontal disease: current concepts. J

Periodontol. 1992;63(4s):322-31. http://dx.doi.org/10.1902/

jop.1992.63.4s.322.

4. Wolff L, Dahlen G, Aeppli D. Bacteria as risk markers for

periodontitis. J Periodontol. 1994;65(5s):498-510. http://dx.doi.

org/10.1902/jop.1994.65.5s.498.

5. Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine

DH,et al. Periodontitis: consensus report of workgroup 2 of

the 2017 World Workshop on the Classification of Periodontal

and Peri‐Implant Diseases and Conditions. J Periodontol.

2018;89(Suppl 1):S173-82. http://dx.doi.org/10.1002/JPER.17-

0721. PMid:29926951.

6. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal

diseases. Nat Rev Dis Primers. 2017;3(1):17038. http://dx.doi.

org/10.1038/nrdp.2017.38. PMid:28805207.

7. Berezow AB, Darveau RP. Microbial shift and periodontitis.

Periodontol 2000. 2011;55(1):36-47. http://dx.doi.org/10.1111/

j.1600-0757.2010.00350.x. PMid:21134227.

8. Marsh PD. Are dental diseases examples of ecological

catastrophes? Microbiology. 2003;149(Pt 2):279-94. http://

dx.doi.org/10.1099/mic.0.26082-0. PMid:12624191.

9. Keestra JA, Grosjean I, Coucke W, Quirynen M, Teughels W. Non-

surgical periodontal therapy with systemic antibiotics in patients

with untreated chronic periodontitis: a systematic review and

meta-analysis. J Periodontal Res. 2015;50(3):294-314. http://

dx.doi.org/10.1111/jre.12221. PMid:25142259.

10. Haffajee AD, Teles RP, Socransky SS. The effect of periodontal

therapy on the composition of the subgingival microbiota.

Periodontol 2000. 2006;42(1):219-58. http://dx.doi.org/10.1111/

j.1600-0757.2006.00191.x. PMid:16930312.

11. Jepsen S, Deschner J, Braun A, Schwarz F, Eberhard J. Calculus

removal and the prevention of its formation. Periodontol

2000. 2011;55(1):167-88. http://dx.doi.org/10.1111/j.1600-

0757.2010.00382.x. PMid:21134234.

12. Feres M, Figueiredo LC, Soares GM, Faveri M. Systemic

antibiotics in the treatment of periodontitis. Periodontol

2000. 2015;67(1):131-86. http://dx.doi.org/10.1111/prd.12075.

PMid:25494600.

13. Van der Sluijs M, Van Der Sluijs E, Van Der Weijden F, Slot DE.

The effect on clinical parameters of periodontal inflammation

following non-surgical periodontal therapy with ultrasonics and

chemotherapeutic cooling solutions: a systematic review. J Clin

Periodontol. 2016;43(12):1074-85. http://dx.doi.org/10.1111/

jcpe.12613. PMid:27509308.

14. Segarra-Vidal M, Guerra-Ojeda S, Vallés LS, López-Roldán A,

Mauricio MD, Aldasoro M,etal. Effects of photodynamic therapy

in periodontal treatment: A randomized, controlled clinical trial.

J Clin Periodontol. 2017;44(9):915-25. http://dx.doi.org/10.1111/

jcpe.12768. PMid:28667678.

15. Teughels W, Durukan A, Ozcelik O, Pauwels M, Quirynen M,

Haytac MC. Clinical and microbiological effects of Lactobacillus

reuteri probiotics in the treatment of chronic periodontitis:

a randomized placebocontrolled study. J Clin Periodontol.

2013;40(11):1025-35. http://dx.doi.org/10.1111/jcpe.12155.

PMid:24164569.

16. Longo M, Ramos TCS, Nunes CMM, Santamaria MP, Jardini MAN.

Probiotic therapy as a novel approach in the prevention and

treatment of gingivitis: a review. Braz Dent Sci. 2018;21(4):367-

76. http://dx.doi.org/10.14295/bds.2018.v21i4.1600.

17. Stamatova I, Meurman JH. Probiotics and periodontal disease.

Periodontol 2000. 2009;51(1):141-51. http://dx.doi.org/10.1111/

j.1600-0757.2009.00305.x. PMid:19878473.

18. Sliepen I, Van Damme J, Van Essche M, Loozen G, Quirynen M,

Teughels W. Microbial interactions influence inflammatory host

cell responses. J Dent Res. 2009;88(11):1026-30. http://dx.doi.

org/10.1177/0022034509347296. PMid:19828891.

19. Twetman S, Derawi B, Keller M, Ekstrand KIM, Yucel-

Lindberg LAY, Stecksén-Blicks C. Short-term effect of

chewing gums containing probiotic Lactobacillus reuteri on

the levels of inflammatory mediators in gingival crevicular

fluid. Acta Odontol Scand. 2009;67(1):19-24. http://dx.doi.

org/10.1080/00016350802516170. PMid:18985460.

20. Brown AC, Valiere A. Probiotics and medical nutrition therapy.

Nutr Clin Care. 2004;7(2):56-68. PMid:15481739.

21. Bron PA, van Baarlen P, Kleerebezem M. Emerging molecular

insights into the interaction between probiotics and the host

intestinal mucosa. Nat Rev Microbiol. 2011;10(1):66-78. http://

dx.doi.org/10.1038/nrmicro2690. PMid:22101918.

22. Mu Q, Tavella VJ, Luo XM. Role of Lactobacillus reuteri in human

health and diseases. Front Microbiol. 2018;9:757. http://dx.doi.

org/10.3389/fmicb.2018.00757. PMid:29725324.

23. Spinler JK, Sontakke A, Hollister EB, Venable SF, Oh PL, Balderas

MA,et al. From prediction to function using evolutionary

genomics: human-specific ecotypes of lactobacillus reuteri have

diverse probiotic functions. Genome Biol Evol. 2014;6(7):1772-89.

http://dx.doi.org/10.1093/gbe/evu137. PMid:24951561.

24. Schepper JD, Collins FL, Rios-Arce ND, Raehtz S, Schaefer

L, Gardinier JD,etal. Probiotic lactobacillus reuteri prevents

postantibiotic bone loss by reducing intestinal dysbiosis and

preventing barrier disruption. J Bone Miner Res. 2019;34(4):681-

98. http://dx.doi.org/10.1002/jbmr.3635. PMid:30690795.

25. Thomas CM, Hong T, van Pijkeren JP, Hemarajata P, Trinh DV,

Hu W, etal. Histamine derived from probiotic lactobacillus

reuteri suppresses tnf via modulation of pka and erk signaling.

PLoS One. 2012;7(2):e31951. http://dx.doi.org/10.1371/journal.

pone.0031951. PMid:22384111.

26. Gu Q, Zhang C, Song D, Li P, Zhu X. Enhancing vitamin

B12 content in soy-yogurt by Lactobacillus reuteri. Int J

Food Microbiol. 2015;206:56-9. http://dx.doi.org/10.1016/j.

ijfoodmicro.2015.04.033. PMid:25955289.

27. Collins FL, Rios-Arce ND, Schepper JD, Parameswaran N, McCabe

LR. The potential of probiotics as a therapy for osteoporosis.

Microbiol Spectr. 2017;5(4):5.4.20. http://dx.doi.org/10.1128/

microbiolspec.BAD-0015-2016. PMid:28840819.

28. D’Amelio P, Sassi F. Gut microbiota, immune system, and bone.

Calcif Tissue Int. 2018;102(4):415-25. http://dx.doi.org/10.1007/

s00223-017-0331-y. PMid:28965190.

29. Iniesta M, Herrera D, Montero E, Zurbriggen M, Matos AR, Marín

MJ,etal. Probiotic effects of orally administered Lactobacillus

reuteri-containing tablets on the subgingival and salivary

microbiota in patients with gingivitis. A randomized clinical

trial. J Clin Periodontol. 2012;39(8):736-44. http://dx.doi.

org/10.1111/j.1600-051X.2012.01914.x. PMid:22694350.

30. Schaefer L, Auchtung TA, Hermans KE, Whitehead D,

Borhan B, Britton RA. The antimicrobial compound reuterin

(3-hydroxypropionaldehyde) induces oxidative stress via interaction

with thiol groups. Microbiology (Reading). 2010;156(Pt 6):1589-99.

http://dx.doi.org/10.1099/mic.0.035642-0. PMid:20150236.

Braz Dent Sci 2023 Jan/Mar;26 (1): e3619

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic efficient as adjunctive therapy in the treatment of periodontitis? A systematic review.

Tricoly TS et al.

Is the use of Lactobacillus reuteri probiotic eﬃcient as

adjunctive therapy in the treatment of periodontitis? A

systematic review.

31. Jones SE, Versalovic J. Probiotic Lactobacillus reuteri biofilms

produce antimicrobial and anti-inflammatory factors. BMC

Microbiol. 2009;9(1):35. http://dx.doi.org/10.1186/1471-2180-

9-35. PMid:19210794.

32. Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz

G. Decreased gum bleeding and reduced gingivitis by the

probiotic Lactobacillus reuteri. Swed Dent J. 2006;30(2):55-60.

PMid:16878680.

33. Riccia DN, Bizzini F, Perilli MG, Polimeni A, Trinchieri V, Amicosante

G,etal. Anti-inflammatory effects of Lactobacillus brevis (CD2)

on periodontal disease. Oral Dis. 2007;13(4):376-85. http://

dx.doi.org/10.1111/j.1601-0825.2006.01291.x. PMid:17577323.

34. Harini PM, Anegundi RT. Efficacy of a probiotic and chlorhexidine

mouth rinses: a short-term clinical study. J Indian Soc Pedod

Prev Dent. 2010;28(3):179-82. http://dx.doi.org/10.4103/0970-

4388.73799. PMid:21157050.

35. Vivekananda MR, Vandana KL, Bhat KG. Effect of the probiotic

Lactobacilli reuteri (Prodentis) in the management of

periodontal disease: preliminary randomized clinical trial. J Oral

Microbiol. 2010;2(1):2. http://dx.doi.org/10.3402/jom.v2i0.5344.

PMid:21523225.

36. Vicario M, Santos A, Violant D, Nart J, Giner L. Clinical changes

in periodontak subjects with the probiotic Lactobacillus reuteri

Prodentis: a preliminar randomized clinical trial. Acta Odontol

Scand. 2013;71(3-4):813-9. http://dx.doi.org/10.3109/0001635

7.2012.734404. PMid:23176716.

37. Teughels W, Durukan A, Ozcelik O, Pauwels M, Quirynen M, Haytac

MC. Clinical and microbiological effects of Lactobacillus reuteri

probiotics in the treatment of chronic periodontitis: a randomized

placebo-controlled study. J Clin Periodontol. 2013;40(11):1025-35.

http://dx.doi.org/10.1111/jcpe.12155. PMid:24164569.

38. Dhaliwal PK, Grover V, Malhotra R, Kapoor A. Clinical and

microbiological investigation of the effects of probiotics

combined with scaling and root planing in the management of

chronic periodontitis: a randomized, controlled study. J Int Acad

Periodontol. 2017;19(3):101-8. PMid:31473697.

39. Grusovin MG, Bossini S, Calza S, Cappa V, Garzetti G, Scotti E,etal.

Clinical efficacy of Lactobacillus reuteri-containing lozenges in

the supportive therapy of generalized periodontitis stage III and

IV, grade C: 1-year results of a double-blind randomized placebo-

controlled pilot study. Clin Oral Investig. 2020;24(6):2015-24.

http://dx.doi.org/10.1007/s00784-019-03065-x. PMid:31620939.

40. Elazim MMA, Kabil NS, Wassel MO, Nasser MS. Investigation of

the effect of breast milk, probiotic supplemented and plain milk

formulas on some oral bacteria in infants: an observational and

in-vitro study. Braz Dent Sci. 2022;25(2):e3099. http://dx.doi.

org/10.4322/bds.2022.e3099.

41. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC,

Mulrow CD, et al. The PRISMA 2020 statement: an updated

guideline for reporting systematic reviews. BMJ. 2021;372:71.

http://dx.doi.org/10.1136/bmj.n71.

42. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting

items for systematic reviews and meta-analyses: the PRISMA

statement. BMJ. 2009;339:b2535. http://dx.doi.org/10.1136/

bmj.b2535. PMid:19622551.

43. Ikram S, Hassan N, Raffat MA, Mirza S, Akram Z. Systematic

review and meta-analysis of double-blind, placebo-controlled,

randomized clinical trials using probiotics in chronic periodontitis.

J Investig Clin Dent. 2018;9(3):e12338. http://dx.doi.org/10.1111/

jicd.12338. PMid:29604177.

44. Ikram S, Hassan N, Baig S, Borges KJJ, Raffat MA, Akram Z. Effect

of local probiotic (Lactobacillus reuteri) vs systemic antibiotic

therapy as an adjunct to non-surgical periodontal treatment in

chronic periodontitis. J Investig Clin Dent. 2019;10(2):e12393.

http://dx.doi.org/10.1111/jicd.12393. PMid:30663271.

45. Ince G, Gürsoy H, İpçi ŞD, Cakar G, Emekli-Alturfan E, Yılmaz

S. Clinical and biochemical evaluation of lozenges containing

lactobacillus reuteri as an adjunct to non-surgical periodontal

therapy in chronic periodontitis. J Periodontol. 2015;86(6):746-

54. http://dx.doi.org/10.1902/jop.2015.140612. PMid:25741580.

46. Pelekos G, Ho SN, Acharya A, Leung WK, McGrath C. A double-

blind, paralleled-arm, placebo-controlled and randomized

clinical trial of the effectiveness of probiotics as an adjunct in

periodontal care. J Clin Periodontol. 2019;46(12):1217-27. http://

dx.doi.org/10.1111/jcpe.13191. PMid:31479530.

47. Pelekos G, Acharya A, Eiji N, Hong G, Leung WK, McGrath C. Effects

of adjunctive probiotic L. reuteri lozenges on S/RSD outcomes at

molar sites with deep pockets. J Clin Periodontol. 2020;47(9):1098-

107. http://dx.doi.org/10.1111/jcpe.13329. PMid:32511775.

48. Szkaradkiewicz AK, Stopa J, Karpiński TM. Effect of oral

administration involving a probiotic strain of Lactobacillus

reuteri on pro-inflammatory cytokine response in patients

with chronic periodontitis. Arch Immunol Ther Exp (Warsz).

2014;62(6):495-500. http://dx.doi.org/10.1007/s00005-014-

0277-y. PMid:24509697.

49. Tekce M, Ince G, Gursoy H, Dirikan Ipci S, Cakar G, Kadir T,etal.

Clinical and microbiological effects of probiotic lozenges in the

treatment of chronic periodontitis: a 1-year follow-up study. J

Clin Periodontol. 2015;42(4):363-72. http://dx.doi.org/10.1111/

jcpe.12387. PMid:25728888.

50. Vohra F, Bukhari IA, Sheikh SA, Albaijan R, Naseem M,

Hussain M. Effectiveness of scaling and root planing with and

without adjunct probiotic therapy in the treatment of chronic

periodontitis among shamma users and non-users: A randomized

controlled trial. J Periodontol. 2019;91(9):1177-85. http://dx.doi.

org/10.1002/JPER.19-0464. PMid:31985066.

51. Bizzini B, Pizzo G, Scapagnini G, Nuzzo D, Vasto S. Probiotics

and oral health. Curr Pharm Des. 2012;18(34):5522-31. http://

dx.doi.org/10.2174/138161212803307473. PMid:22632388.

52. Baca-Castañón ML, De la Garza-Ramos MA, Alcázar-Pizaña

AG, Grondin Y, Coronado-Mendoza A, Sánchez-Najera RI,etal.

Antimicrobial effect of lactobacillus reuteri on cariogenic

bacteria streptococcus gordonii, streptococcus mutans, and

periodontal diseases actinomyces naeslundii and tannerella

forsythia. Probiotics Antimicrob Proteins. 2015;7(1):1-8. http://

dx.doi.org/10.1007/s12602-014-9178-y. PMid:25422124.

53. Martin-Cabezas R, Davideau JL, Tenenbaum H, Huck O. Clinical

efficacy of probiotics as an adjunctive therapy to non-surgical

periodontal treatment of chronic periodontitis: a systematic

review and meta-analysis. J Clin Periodontol. 2016;43(6):520-30.

http://dx.doi.org/10.1111/jcpe.12545. PMid:26970230.

54. Song D, Liu XR. Role of probiotics containing Lactobacillus

reuteri in adjunct to scaling and root planing for management

of patients with chronic periodontitis: a meta-analysis. Eur Rev

Med Pharmacol Sci. 2020;24(8):4495-505. PMid:32373987.

55. Akram Z, Shafqat SS, Aati S, Kujan O, Fawzy A. Clinical efficacy

of probiotics in the treatment of gingivitis: a systematic review

and meta-analysis. Aust Dent J. 2020;65(1):12-20. http://dx.doi.

org/10.1111/adj.12733. PMid:31682012.

Maria Aparecida Neves Jardini

(Corresponding address)

Universidade Estadual Paulista, Instituto de Ciência e Tecnologia, Departamento de

Diagnóstico e Cirurgia. São José dos Campos, SP, Brazil.

Email: maria.jardini@unesp.br

Date submitted: 2022 Aug 17

Accept submission: 2023 Jan 23