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ORIGINAL ARTICLE
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Evaluation of effect of consumption of probiotics on the gingival and periodontal health status in children undergoing chemotherapy


1 Department of Pediatric Dentistry, Government Dental College and Hospital, Dhanwantarinagar, Maharashtra, India
2 Government Engineering College, Aurangabad, Maharashtra, India

Date of Submission14-Dec-2019
Date of Decision23-Sep-2020
Date of Acceptance09-Oct-2020
Date of Web Publication29-Jun-2022

Correspondence Address:
Chaitali Hambire,
Department of Pediatric Dentistry, Government Dental College and Hospital, Dhanwantarinagar, Maharashtra
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_215_20

  Abstract 


Background: Probiotics consist of live microbes. They do not have any adverse effects on health. They provide nutritive benefits to individuals when ingested in adequate quantities. The most common oral infections of the oral cavity are those affecting the periodontal and dental tissues.
Aims and Objectives: 1) To evaluate the antimicrobial role of oral probiotics against microorganisms involved in infections of periodontal and dental tissues. 2) To evaluate the state of health of gingival and periodontal tissues of children undergoing chemotherapy after the use of oral probiotics.
Materials and Methods: 60 children, between the age group of 3 and 15 years, undergoing chemotherapy were randomly distributed under control and probiotics administered test group for 90 days. The gingival, periodontal, and oral hygiene statuses were evaluated along with their caries activity test. The parameters were measured at 0, 15, 30, 45, 60, 75, and 90 days intervals. Statistical analysis was performed using Statistical Package for the Social Sciences version 18.0.
Results: The oral probiotics consumption significantly reduced the plaque accumulation between days of observation among those in the treatment group (P < 0.05). There was a significant improvement in the gingival and periodontal status in the tested group (P < 0.05). Snyder test was conducted to assess caries activity. Score 1 was found in 10 children, score 2 in eight children. Score 3 was not found in any child under the study group.
Conclusion: The results show that the regular consumption of oral probiotics significantly reduces plaque accumulation, calculus formation, and caries activity among the test group.


Keywords: Chemotherapy, dental caries, dental plaque, oral hygiene index, probiotics



How to cite this URL:
Hambire C, Hambire U. Evaluation of effect of consumption of probiotics on the gingival and periodontal health status in children undergoing chemotherapy. Indian J Cancer [Epub ahead of print] [cited 2022 Aug 7]. Available from: https://www.indianjcancer.com/preprintarticle.asp?id=348454





  Introduction Top


National Cancer Institute defines pediatric cancer as cancer occurring between birth and 15 years of age.[1] These are rare and differ from adult cancers in terms of their growth, spread, treatment, and response to the treatment. They are also called childhood cancer. The incidence of pediatric cancer is more in developed countries than in developing counties like India. In developing countries, the pediatric cancer account for 2% of malignancies.[2] Every year around 45,000 children in India are diagnosed with cancer, of which 40 to 50% is leukemia and 15 to 20% is lymphoma. Children between 5 and 14 years are most commonly affected. The boys are affected more than girls.[3] Acute lymphoblastic leukemia (ALL) is the most common leukemia with an incidence of 3 to 4 cases per one lakh children below 15 years of age. Chemotherapy is the main line of treatment for Acute Lymphoblastic Leukemia. Drugs used in chemotherapy for cancer damage the cells undergoing rapid multiplication such as bone marrow, follicular cells of hair, and cells lining the mucosa of the oral cavity and intestine.[4],[5] They also affect normal oral micro-flora. Around 40% to 90% of children undergoing chemotherapy develop oral manifestations. The most common manifestations are mucositis, dry mouth (xerostomia), pain, parageusia (dysfunction of taste sensation), dental caries, salivary gland dysfunction, and opportunistic infections.[6]

In 1965, Lilly and Stillwell coined the term “probiotics” which means life in the Greek language.[7] The World Health Organization (WHO) in 2001 defined probiotics as “live microorganisms when consumed in proper quantities provide advantages to the health of the individual.”[8] Microbes release numerous chemicals like hydrogen peroxide, bacteriocins, and others, having definitive bactericidal properties. They act at the mucosal sites of adhesion by competitive inhibition and thus prevent the colonization of pathogenic microorganisms. They exert changes in pH by altering the redox potential (oxidation-reduction potential), which in turn, affects the capacity of the microorganisms to thrive in the oral environment. Finally, probiotics trigger nonspecific immunity in individuals and alter their immune mechanisms (both cellular and humoral). Lactogenic bacteria may exert their modulating influence on immune competent cells like T cells and macrophages. This may impact the cytokine production in these cells and thus may influence the overall immune response of individuals. Combinations of probiotic strains have a synergistic effect and this is used to increase the beneficial effects.[9]

Patients undergoing chemotherapy and radiotherapy for cancer treatment become immune-compromised. There is a disturbance in homeostasis resulting in the emergence of multiple resistant strains and colonization of pathologic microorganisms. Disturbance in the oral microbiome homeostasis can lead to the development of dental caries, periodontal diseases, and opportunistic infections like mucositis, oral candidiasis. Studies have shown that probiotics have been effective in strengthening homeostasis and decrease the toxic effects of chemotherapy. Probiotics are cost-effective and readily available for patients. Probiotics have been shown to maintain the oral ecological equilibrium by their natural colonization. The role of probiotics has been studied in the prevention and reduction of complications of chemotherapy such as diarrhea and mucositis.[10] Very few studies have been done to evaluate the effectiveness of the use of oral probiotics in children undergoing cancer treatment in form of chemotherapy and radiotherapy.[11] The findings of this study may help the researchers and consumers regarding the use of oral probiotics as an adjunctive in the management of oral manifestations of chemotherapy in children. Hence this study was conducted with the following aims and objectives: 1) To evaluate the antimicrobial role of oral probiotics against microorganisms involved in infections of periodontal and dental tissues. 2) To evaluate the state of health of gingival and periodontal tissues of children undergoing chemotherapy after the use of oral probiotics.


  Materials and Methods Top


Subjects

The study was approved and conducted according to the ethical standards established by the Institutional Ethical Board (Approval No. 001108/GDCHA/IEBTRE/EC/2016) and Helsinki Declaration of 1975, revised in 2000 and 2008. Informed consent was obtained from the parents of the children both verbally and in writing. No incentives were offered for this study.

Sample size

The sample size was calculated using the following formula[12]:

n = 2 (Zα + Z [1-β])2 × p × q/d2

Where n = sample size, Zα = Z is constant set by convention according to accepted α error, and Z (1-β) is constant set by convention according to the power of the study. We have set the acceptable limit for alpha (P-value) less than 0.05. The “power” of the study then is equal to (1-β) and for a β of 0.2, the power is 0.8, which is the minimum power required to accept the null hypothesis. The effect size (ES) was estimated by using previously reported data as 20% along with a dropout rate of 30% in each group. Proportions obtained from the previous study were 10%. A reduction in the incidence of dental caries activity up to 20% would be considered significant for the effectiveness of oral probiotics.

P1 = 20%, P2 = 10%, Effect size = 20%, Zα = 1.96, Z (1-β) = 0.842, d = 30

Average of P1 and P2 will be p = P1 + P2/2 20 + 10/2 = 15

q = 1-p = 1-15 = 85%

n = 2 (1.96 + 0.842)2 × 20 × 85/(30)2 = 29.659

Based on these calculations 30 children were to be included in each group for the study. Hence, a total of 60 children were recruited for the study.

Sample population

Children between 3 and 15 years, diagnosed with Acute Lymphoblastic Leukemia and Lymphoma, undergoing chemotherapy in Government Cancer Hospital were selected. Children who had not started chemotherapy or those who completed their chemotherapy were excluded from the study.

Study design

It was a prospective study conducted from August 2019 to November 2019 on 60 children. The study population was divided into two groups, each having 30 children, by simple randomization method using a lottery. The study group was given oral probiotics and an oral hygiene kit (toothbrush and toothpaste). The control group was only given an oral hygiene kit (toothbrush and toothpaste).

The medical histories along with the details of chemotherapy were recorded. Detailed information about their oral hygiene measures was recorded. The dietary uptake of food products containing lactic acid was also recorded. Children were instructed to avoid the intake of food containing probiotics for one month prior to the beginning of the study.

The parents were educated and motivated regarding the proper brushing technique of their wards. The study group was instructed to drink one bottle of probiotics two hours after tooth brushing. The study group was asked to continue this process for 90 days duration. The control group was asked to do daily tooth brushing without consuming oral probiotics. Recall visits were scheduled for all the participants belonging to both groups (study and control) at the 15, 30, 45, 60, 75, and 90 days intervals [Figure 1].
Figure 1: Study design

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Oral examination

Sterile mouth mirrors and disposable sterile gloves were used to conduct the oral examination of the study and control group. The numbers of decayed, missing, and filled teeth were recorded at baseline, 15, 30, 45, 60, 75, and 90 days intervals. Data regarding oral hygiene, dental plaque, and salivary parameters (pH, buffering capacity, and salivary flow rate) were also collected at these intervals. Those variables were used to define caries risk factors. Oral hygiene participants were examined based on the parameter Oral Hygiene Index-Simplified (OHI-S) of Greene and Vermilion which consists of two parts, debris index, and calculus index. Each of these is based on numerical determination representing the amount of debris or calculus on index tooth surfaces. Silness-Löe plaque index was used to measure the accumulation of plaque among groups. Unstimulated saliva was collected to measure pH, buffering capacity, and salivary flow rate. Snyder test was conducted to measure the caries activity.

Statistical analysis

The data was collected by a single trained and calibrated examiner (Kappa equal to 0.86). In the present study, there were no dropouts. The collected data were statistically analyzed using the Statistical Package for Social Sciences System (SPSS) version 18.0. A paired t-test was used for comparison between before and after intervention values of the same group and Chi-square test for grouping variable. Subsequently, comparison variables between baseline and follow-up examination were done by ANOVA test. P-value equal to 0.05 or less was considered to be statistically significant.


  Results Top


Thirty children consumed oral probiotics for 90 days. The baseline characteristics of participants are presented in [Table 1], where no statistical difference was present between the control and study group. [Table 2] shows a significant difference in the plaque index among the study group and the control group. It is shown that after 90 days of consumption of oral probiotics, the plaque index was significantly reduced. The mean value of debris index, calculus index, and OHI-S reduced on day 90 compared to day 0 and day 45, while the mean value of pH saliva was increased from baseline to day 90. Among all variables, plaque index and calculus index were found to have a significant difference between days of observation. These results showed that plaque index was found to significantly reduce from baseline to day 90 and calculus index was found to have a significant difference after 45 days using the probiotics. However, the mean value of debris index and OHI-S was tending to reduce on day 90 compared to day 0 and day 45, while the mean value of pH saliva was increased from day 0 to 90 [Graph 1]. [Table 3] shows the reduction in caries activity in the test group after a period of 90 days. Snyder test was conducted to assess caries activity. Score 1 was found in 10 children, score 2 in eight children. Score 3 was not found in any child under the study group [Graph 2].
Table 1: Baseline characteristics of participants

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Table 2: Comparison of variables between untreated and treated group at day 90

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Table 3: Comparison of caries activity test between untreated and treated group at day 90

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  Discussion Top


Each year approximately 38 to 124 per million children are affected with pediatric cancer in India. The most common pediatric cancer is ALL followed by lymphoma. Chemotherapy is the main line of treatment. There are many serious side effects like alopecia, fatigue, hematological, and gastrointestinal toxicity. Chemotherapy also alters the natural flora present in the body. This alteration leads to various side effects like diarrhea and mucositis.[13] Recently various studies have shown that probiotics have beneficial effects of modulating host immune response, enhancement of antioxidant activity, degradation of potential carcinogens, and improvement of natural microflora.[14]

Dental plaque is a cohort of microorganisms found on the surface of the tooth as a biofilm. The microorganisms are embedded in a complex matrix of polymers derived from the host and bacteria. Dental plaque has a significant role in the pathogenesis of dental and periodontal diseases. It provides a favorable place for the growth of pathological microorganisms as well as protects them from antimicrobial agents. Irregular and incomplete removal of dental plaque leads to various oral health issues like dental caries, gingivitis, and periodontitis.[15] Probiotics decrease the plaque formation by neutralization of free electrons, regulating the mucosal permeability, and modulating the systemic immune response. The significant role of probiotics in the prevention and management of mucositis, halitosis, candidiasis, dental, and periodontal diseases has been suggested by various studies.[16]

There is a paucity of data on the effect of oral probiotics on dental caries activity, salivary pH, and oral hygiene amongst children undergoing chemotherapy.[17] In this study, there was a significant reduction in plaque in the study group at the end of 90 days. The calculus index was significantly reduced after consuming oral probiotics per day. The pH of saliva was increased in the study group. This could be due to the concept that the beneficial and nonpathogenic microorganisms present in the probiotics inhabit the dental plaque biofilm and protect the oral and dental tissues.[18] The casein phosphopeptide present in the probiotics neutralizes the acid produced by the cariogenic bacteria and promotes remineralization.[19] The beneficial effects of probiotics in the reduction of caries activity have been shown in healthy children but no study has been done on children undergoing chemotherapy. In our study, the oral probiotics were well tolerated by the children and there were no dropouts. The caries activity was also reduced in the study group.[20]

Probiotics prevent the attachment of pathogenic micro-organisms to tissues. It reduces the production of pro-inflammatory cytokines by its actions on NFkB (nuclear factor kappa light chain enhancer of activated B cells) pathways thereby increasing production of anti-inflammatory cytokines such as Interleukins 10 (IL-10) and host defense peptides such as b defensin 2, enhancing Immunoglobulin A (IgA) defenses and influencing dendritic cell maturation. It produces bacteriocins that kill or inhibit the growth of pathogens.[21],[22] Probiotics interferes with mechanisms involved in the attachment of oral microflora with the proteins thereby preventing the plaque biofilm formation.[21] The probiotics have shown anticarcinogenic abilities.[23] Results of previous studies have shown that probiotics improve the mucositis induced by chemotherapy.[24],[25]

The strength of the present study is that it was conducted on children suffering from ALL and lymphoma undergoing chemotherapy. They were randomly divided into two groups to avoid any bias. A comparison between the test and the control group could be made. The limitations of the study were small study populations and short study duration. Nevertheless, the results of this study are promising to advocate the use of oral probiotics in the reduction of plaque, dental caries activity, and an increase in salivary pH. Probiotics can be proposed as an effective tool in preventing caries when used with good oral hygiene regimes.


  Conclusion Top


Oral probiotics have been found to be significant in the reduction of plaque and increase in salivary pH in our present study. The practical application of oral probiotics along with tools of oral hygiene is an efficacious way of reducing plaque and calculus formation in children undergoing chemotherapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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National Cancer Institute. Childhood cancer genomics gaps and opportunities: Identification of research priorities workshop summary. 2015:1-33.  Back to cited text no. 1
    
2.
Das S, Paul DK, Anshu K, Bhakta S. Childhood cancer incidence in India between 2012 and 2014: Report of a population-based cancer registry. Indian Pediatr 2017;54:1033-6.  Back to cited text no. 2
    
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Bashar MA, Thakur JS. Incidence and pattern of childhood cancers in India: Findings from population-based cancer registries. Indian J Med Paediatr Oncol 2017;38:240-1.  Back to cited text no. 3
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Asthana S, Labani S, Mehrana S, Bakhshi S. Incidence of childhood leukemia and lymphoma in India. Pediatr Hematol Oncol J 2018;3:115-20.  Back to cited text no. 5
    
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Berger D, Zandonade E, Monteiro de Barros Miotto MH. Prevalence of oral manifestations in children and adolescents with cancer submitted to chemotherapy. BMC Oral Health 2016;16:107.  Back to cited text no. 6
    
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Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. The International scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11:506-14.  Back to cited text no. 8
    
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Tiwana MS, Mahajan MK, Uppal B, Koshy G, Sachdeva J, Lee HN, et al. Whole saliva physico-biochemical changes and quality of life in head and neck cancer patients following conventional radiation therapy: A prospective longitudinal study. Indian J Cancer 2011;48;289-95.  Back to cited text no. 9
    
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Mego M, Holec V, Drgona L, Hainova K, Ciernikova S, Zajac V. Probiotic bacteria in cancer patients undergoing chemotherapy and radiation therapy. Complement Ther Med 2013;712-23.  Back to cited text no. 14
    
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Marttinen A, Haukioja A, Karjalainen S, Nylund L, Satokari R, Öhman C, et al. Short-term consumption of probiotic lactobacilli has no effect on acid production of supragingival plaque. Clin Oral Investig 2012;16:797-803.  Back to cited text no. 18
    
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Singh RP, Damle SG, Chawla A. Salivary mutans streptococci and lactobacilli modulations in young children on consumption of probiotic ice-cream containing Bifidobacteriumlactis Bb12 and Lactobacillus acidophilus La5. Acta Odontol Scand 2011;69:389-94.  Back to cited text no. 24
    
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Tsai Y-L, Lin T-L, Chang C-J, Wu T-R, Lai W-F, Lu C-C, et al. Probiotics, prebiotics and amelioration of diseases. J Biomed Sci 2019;26:3.  Back to cited text no. 25
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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