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Abstract

Objectives & Introduction

It is possible to damage the natural intestinal barrier following severe burn injuries. Oral probiotics' positive effects on the innate immune system or intestinal epithelial layer are proven. This research aimed to evaluate the role of probiotics on plasma inflammatory changes and bacterial colonization in the burned wound after high-grade thermal trauma.

Methods

This double-blinded randomized controlled trial was conducted on 80 patients with a total body surface area of 20–70%. Patients were allocated to two groups based on four blocks randomization model. Intervention and control groups received daily LactoCare and placebo capsules for 14 consecutive days. Obtaining demographic data, burn and gastrointestinal symptoms were registered by filling out a questionnaire. Additionally, measuring plasma levels of highly sensitive C-reactive protein(hs-CRP), IgA, absolute neutrophilic, and lymphocytic count were performed cumulatively four times prior to and after the intervention.

Results

Considering eligible data, following the study period analysis showed significant mitigation of inflammatory status in probiotic receivers. The hs-CRP reduced following probiotic (21.38 ± 44.45) consumption compared with placebo (−36.36 ± 79.03) intake (p < 0.001). Also, the plasma level of IgA significantly decreased in the intervention group (0.88 ± 0.65) than in the control group (0.79 ± 0.18) (p < 0.001). Wound cultures showed no significant difference between groups, although the incidence rate of bacterial colonization was slightly lower after using probiotics (p = 0.159). Regarding wound healing, data illustrated that probiotics could accelerate wound healing after 14 days of regular consumption (p < 0.001).

Conclusion

Probiotics have advantages for the mitigation of inflammation and wound healing following severe thermal burn injuries. Trends toward Improvement Immune system by increasing IgA level and lymphocytic count and possible Reduction of wound area with exogenous probiotic administration in patients with burns suggest that further investigation in larger sample size is necessary to corroborate our initial, promising findings.

Keywords

Burn CRP IgA Probiotics Wound healing

Introduction

Burns is one of the most expensive traumatic events that lead to a long period of hospitalization and high costs for the repair of the wounds and following complications. About 300,000 people worldwide die from burns yearly, mainly in developing and underdeveloped countries. Due to the advancement of medical knowledge and health care services in recent few decades mortality rate related to burn injuries has decreased globally, although morbid side effects remain unchanged.^1–4

Previously local infection of the wound site was considered as paramount reason for post burning sepsis.⁴ Despite the prescription of broad-spectrum antibiotics, the development of dressing materials and techniques, and upgraded surgical approaches incidence of sepsis has slightly decreased. The latter part has been explained by bacterial translocation of intestinal flora to the bloodstream following systemic effects of burn injury. During this phenomenon, the bacteria pass through the mucosal barrier of the digestive system and could be colonized in the liver, spleen, bloodstream, and mesenteric lymph nodes.⁵

Innately, the normal flora of the healthy intestine prevents the pathologic translocation of microorganisms with different mechanisms, which is disrupted following severe burning.⁶ The normal flora of the intestine plays important roles including absorption of food, production of different vital metabolites, signaling intestinal epithelia, and reinforcement of function of the immune system by precluding invasive pathogens.⁷ Furthermore, the intestinal mucosal layer act as a local defensive barrier preventing either bacteria or endotoxins that normally exist in the area from penetration to extra-intestinal space.⁵ Preservation of the latter needs normal mesenteric blood flow, which is disturbed following burn injuries concurrent with physiological stress.⁸

Except for mesenteric blood flow disruption, extensive burning directly leads to blood flow shunting towards the site of injury and more oxygen consumption, which finally concludes in hypoxemia and free radical production, negatively influencing other tissues, including gastrointestinal(GI) tract.⁶ Next, GI ischemia occurs, and the stressful digestive system plays a role as a pro-inflammatory source; following splenic perfusion reduction, inflammatory factors are released from the digestive system, which causes disruption of cell function and activation of neutrophils and other pro-inflammatory cells. One of the results of the latter is bacterial immigration to extraluminal space followed by the temporary weakness of the innate immune, intestinal barrier.^5,6 Recently, advocates of the hypothesis of reinforcing intestinal barrier integrity with adding intestinal flora to deal with the aformentiond pathology have increased.^6,9 Probiotics consist of live microorganisms helping host’s intestinal immune system against bacterial expansion specifically through functional improvement of Tol-like receptor 2(TLR2), activiation of intestinal epithelial cells, qualification of phagocytosis, and production of specific antibodies in plasma.^9–12 Probiotics consist of live microorganisms helping the host’s intestinal immune system against bacterial expansion, specifically through the functional improvement of Tol-like receptor 2(TLR2), activation of intestinal epithelial cells, qualification of phagocytosis, and production of specific antibodies in plasma.¹³

The main strains of probiotics include Lactobacillus Acidophilus, Lactobacillus casei, and some species of bifidobacterium colonizing in human’s small intestine and inhibiting the growth of pathogenic microorganisms through the production of organic acids, cytokines, and bacteriocidal factors.^12,14 Further, other approved immune enhancing mechanisms directly related to probiotics can point to increasing numbers of macrophages and natural killer cells, production of hydrogen peroxide(H2O2) and lactic acid, prevention of anchoring pathogens to intestinal cells, and mitigation of inflammatory response caused by the pathogen.^12,15,16

Probiotics bacteria also influence the immunological defense and inflammation system by the production of diverse cytokines that enhance the reaction of the immunological system to pathogens, enhancement of the phagocytic capabilities of polymorphonuclears, augmentation of natural killer cell activity, and amplification of production of specific antibodies and immunoglobulins against pathogenic bacteria. According to the aforementioned data and regarding the feasible availability and low expense of probiotics preparation in association with no significant side effects, it should be studied to find benefits, if any, of using such microorganisms in the treatment of selected cases. However, there have been few efforts to evaluate the possible benefits of the administration of probiotics in burn injury, so In the current study, we aimed to evaluate the effects of probiotics in selected burned patients on plasma inflammatory status and wound healing.

Methods

Participants

In this double-blind, randomized clinical trial, a total of 80 patients from Velayat Sub-Specialty Burn and Plastic Surgery Center in Guilan Province, Rasht, Iran, from May 2021 to February 2022. The ethics board of Guilan University of Medical Sciences, Rasht, Iran, approved the study protocol (reference number: IR.GUMS.REC.1400.303). All patients provided written informed consents, and All procedures were by the tenants of the Declaration of Helsinki and its later amendments.¹⁷ This trial was registered at http://www.irct.ir as IRCT20210524051384N3.

The sample size considering the power of the test of 80%, the error level 0.05 and the standard deviation of 2.2 (probiotic group) and 9.7 (control group) and d = 4.65, by applying 10% drop, was obtained 40 for each group.¹⁸ The inclusion criteria were as follows: burn degree of 20–70% of total body surface area (TBSA); second degree patients with thermal burns; hospitalization within 24 h post-burn; age range of 18–60 years; body mass index (BMI) of 18–30 kg/m2; ability to eat and drink through the mouth; and willingness to participate in the study. On the other hand, patients with renal or hepatic failure, diabetes mellitus, connective tissue disorders, history of chemotherapy, malnutrition at admission, or need for parenteral or enteral nutritional support and mechanical ventilation support and Patients who needed a skin graft during the 14 days of intervention were excluded from the trial. Among 584 patients who were initially enrolled in this study, 87 met the inclusion criteria and entered the study. However, five patients died during the intervention (Figure 1).

Figure 1.

CONSORT flow diagram of subject enrollment, allocation, follow-up, and analysis.

Randomization

Eligible patients were allocated to two groups through a 1:1 stratified four blocks randomization method based on gender and degree of burning. It was performed by a blinded third-party administrator of the SAS version nine software. Patients, interventionists, and also an investigator of outcomes were blinded to group allocation.

Intervention

The probiotic product was formed as a capsule containing 109 CFU included L. casei, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium breve, Bifidobacterium longum, Streptococcus thermophiles species, and prebiotic fructo-oligosaccharide as growing and activator factor for probiotic microorganisms. Called LactoCare capsule is designed and produced by Zist Khamtir (ZIST TAKHMIR, Tehran, Iran). Placebo capsule was designed absolutely identically to probiotic counterpart considering size, shape, color, weight, and package filled with starch. Participants, according to their groups, received proper capsules twice a day for oral intake. Capsul consumption last 14 days from the first day of study initiation, which was Maximum within 10 days after the burn injury.¹⁹

Data collection

Demographic data including age, gender, height, educational level, job, drinking alcohol, cigarette smoking, and place of residence was obtained. Disease-related variables included length of hospital stay, antibiotic and/or antifungative treatment, number of skin grafting operations, and graft failure registered. Data related to gastrointestinal discomforts like constipation, diarrhea, vomiting, and the need for laxative use was written as a number of days of the presence of aforementioned morbidities.

Measuring plasma level of high-sensitive C-reactive protein(hs-CRP) (ELISA kit, Wuhan, China), IgA (ELISA kit, Wuhan, China), absolute lymphocytic and the neutrophilic count was done on the previous day of the study initiation for every individual and also rechecked respectively on 12th, 17th, and 24th followingly.

TBSA was calculated by burn fellow on the admission day using the Wallace criteria.²⁰ In this study, constipation was defined as not passing stool for three consecutive days, and diarrhea was defined as passing soft stool more than four times a day or passing two or more watery stools during 24 h.¹⁹ Diarrhea which occurred after taking laxatives, was not taken into count. Diagnosis of wound infection was established while clinical evidence of suppurative discharge, adjacent cellulitis, unpleasant wound odor, fever, de-novo anorexia, tachycardia or tachypnea was presented and approved by following whether blood or wound culture study.

Statistical analysis

Data analysis was performed by Statistical Package for the Social Science (SPSS) version 24 (IBM, Chicago, USA). Quantitative variables were presented by numbers, mean, and standard deviation. Qualitative variables were explained by numbers and percentages. Analysis of the latter was performed using the Chi-squared, Fisher’s Exact, and ANOVA exams. While for comparing parametric data, the Kruskal–Wallis test was applied. The level of significance was defined as calculated p < 0.05.

Results

Of the total 80 eligible enrolled patients, 35 (43.75%) were women, and the rest 45 (56.25%) were men. The mean age was 43.25 ± 13.25 years among all. Most patients (55-49.10%) were between 31 and 50 years of age. Of all, 65.43% lived in urban areas, 52.20% had a high-grade educational degree, and 40.90% were laborers. The mean TBSA in group A was 35% and in group C was 29%, the lowest TBSA was 22% and the highest was 47% in both participant groups. 21 patients were grafted in group A and 24 patients grafted in group C Before the 10th day, and two patients from each group had sepsis with positive blood culture(B/C) between 9th and 24th days. It should be mentioned that the group’s comparison of variables, including sex, age, educational level, occupation, place of residence, and body mass index had no statistically significant difference (p > 0.05) (Table 1).

Table 1.

Comparation of demographic and primary clinical status.


Characteristics		Group A	Group C	p-value
Characteristics		Probiotic(n = 40)	Control (n = 40)	p-value
Sex (M,F)	Male	23	22	0.635*
	Female	17	18	0.635*
Age (year)		43±13	45±15	0.816*
BMI (kg/m²)		26.2±3.9	25.8±3.4	0.451**
TBSA, %		35±10	29±10	0.872***
Grafted patients (n)		21	24	0.528**
Sepsis (n.%)		2 (25%)	2 (22%)	0/637***
Smoke inhalation (n)		23	19	0.604**
Length of hospitalization		18/9±2/6	17/4±2/9	0.548***
Duration of ceftazidime(1g) (days)		7.0±4.0	6.8±3.6	0.824***
Number of days of antifungal medication		3.8±0.3	2.9±1.3	0.937***
Diarrhea (n.%)		0 (0%)	0 (0%)	0.906^*

Chi Square Test, **Fisher’s Exact Test **** Anova.

The mean starting of Capsul consumption was 6.3 ± 1.2 in the control group and in 5.9 ± 0.9 probiotics group which was not statistically significant(p = 0.563). Following 2 weeks of drug usage, no report of gastrointestinal complications was registered, whether in the control or in the intervention group.

The plasma level of hs-CRP dropped obviously following probiotic consumption (p < 0.001). Measurements revealed the latter was 21.38 ± 44.45 and 36.36 ± 79.03 mg/L for probiotic and placebo receivers, respectively. Also, the increased plasma level of IgA among probiotic consumers (89.3 ± 5.65 g/L) was statistically significant compared with the control group (103.18 ± 6.11 g/L) (p < 0.001).

The results of the study showed that absolute neutrophilic count has no considerable difference (p > 0.05), although an increasing change in the absolute lymphocytic count was significant after receiving probiotics (p < 0.001). Table 2 presents data in this regard.

Table 2.

Clinical outcome data at the end of the study.

		Group A	Group C	p-value
Clinical outcome		Probiotic(n = 40)	Control (n = 40)	p-value
IgA (mg/dL)	Before^a	49.65±5.12^*	57.3±5.61^*	0/247^**
	After^b	89.3±5.65^*	103.18±6.11^*	0/001^**
	Change	39.65±0.53^*	45.88±0. 5^*	0/003^**
h.s.CRP (g/dL)	Before^a	52/75±38/16*	64/07±49/86*	0/879^**
	After^b	39/86±31/51*	47/31±41/94*	0/001^**
	Change	12/89±29/96*	16/77±31/04*	0/001^**
Neutrophils (%)	Before^a	79/8±5/8*	78/6±6/9*	0/789^**
	After^b	85/8±4/7*	88/8±5/8*	0/832^**
	Change	6/00±1/1*	10/2±1/1*	0/189^**
Total lymphocyte count (cell/mm3)	Before^a	1908±69*	1864±75*	0/651
	After^b	2569±79*	2209±90*	0/001**
	Change	661±10*	345±15*	0/001**
Wound area (cm²)	diff 9-12^c	10.12±46.32	−5.61±66.93	0.262
	diff 9-17^c	31.79±58.40	128.8±65.37	<0.001
	diff 2-24^c	85.84±63.95	176.7±79.07	<0.001

*mean ± SD **Kruskal Wallise Test.

^a day 9 ^b day 24.

Wound examination and culture study manifested that there was no optimal wound condition prepared following probiotic consumption; however, the incidence rate of positive cultures lowered among the intervention group (p = 0.159).

The total healed area of the wound was obviously increased among probiotic receivers after finishing the study (p < 0.001), although these recovery changes had no prominent difference after the first week of study initiation(p > 0.05) (Figure 2). The study period for all participants was completed, and there was no considerable side effect to report.

Figure 2.

Comparison of the difference in changes (reduction) of wound area in the studied groups.

Discussion

This double-blinded randomized controlled trial has evaluated the effects of oral probiotic intake in selected second or third-degree thermal burn injured patients for a 14 days period of time. An investigation consisted of changes in the plasma index of inflammation and wound characteristics, included of healing and bacterial colonization. The final analysis has implied positive effects on inflammatory mitigation and wound recovery following probiotic consumption. According to the author’s knowledge, this study was the first regarding its specific topic. However, there are many available studies evaluating the effects of probiotics on a different aspects of human health promotion or disease prevention and treatment.

The hs-CRP is known as an acute phase reactant that increases following the most stressful condition, like a traumatic injury. Although the latter leads to an aseptic inflammatory response, an elevated level of hs-CRP directly relates to the patient’s prognosis. Namely, a higher quantitative level of plasma hs-CRP predicts more unfavorable outcomes for the patient²¹ Specifically, in the case of burn injuries, increased level of plasma hs-CRP conforms with higher grade and deeper tissue injury.²² Further, an essay has claimed that plasma level of hs-CRP following burn trauma can predict survivors from victims.²³ Previous data has shown that decreasing mitigation of hs-CRP is associated with better wound healing which is in line with our finding.¹⁰ Other advocates have implied positive effects of probiotic consumption on pediatric recovery after thermal burn injury, prevention of inflammation among intensive care unit admitted patients, and even precluding symptoms of benign histopathologic inflammatory disorders.^18,19,24 They have concluded that probiotics possibly attenuate inflammatory reactive cascade through releasing of anti-inflammatory cytokines. Opponents have not supported of that intaking oral probiotics would lead to inflammatory preclusion, decreasing in plasma level of hs-CRP, or faster discharge from intensive care units.²⁵ Despite such discrepancy in results, it should be mentioned that there is no report of any side effects following probiotic consumption. Therefore, considering safety, availability, and low expense, it can be reasonable to use probiotics in selected cases.

The current study has revealed probiotic consumption is concurrent with increased IgA level and absolute lymphocytic count after the study has been finished on day 14th. Similarly, other authors have presented data about increased plasma levels of IgA among probiotic receivers who suffered from major traumatic injuries.^18,26,27 Also, Alberda et al. reported a significant increase in IgA levels in the treatment group after examining synbiotics in ICU patients.²⁶ In another study, Tahir et al. state that despite the slight difference in septic complications, probiotics have the ability to improve the function of the body’s immune system and provide healthy granulation tissue for better graft survival.²⁸

Considering wound healing, we found sensible recovery and a greater area of healed tissue following probiotic consumption. Although the incidence rate of culture study of injured skin had no obvious difference between groups, positive cultures were slightly lesser than placebo receivers. Alberda et. Has been noticed that probiotics lead to the improvement of immune cell function and the generation of more qualified granulation tissue, causing more successful skin grafts.²⁶

Finally, a current survey has illustrated probiotic consumption plays an anti-inflammatory role and also helps with wound healing in selected burn patients. However, available data and details on this specific issue seem to be not sufficient for approved therapeutic consideration. Therefore, we explicitly recommend the conduction of multicentric studies with larger sample sizes and more long term follow up.

Limitations

This study was performed in a single burn-specific referral center with a limited number of participants. Burning etiologies, except thermal burns, were excluded. Long-term follow-up was not considered. Prescription and analysis of different dosages of probiotics were not planned. Although an attempt was made to match the patients by using the same antibiotic, the use of several types of antifungals was one of the limitations of this study. The inclusion of 20–70% patients was one of the limitations of the study due to the large difference in burn percentage

Conclusion

Intake of oral probiotics, even for a limited time after thermal burn injury, is costly benefited because these microorganisms can enhance the immune system, preclude inflammation, and promote wound healing. Additionally, the consumption of probiotics has no sensible complication. Trends toward Improvement Immune system by increasing IgA level and lymphocytic count and possible Reduction of wound area with exogenous probiotic administration in patients with burns suggest that further investigation in larger sample size is necessary to corroborate our initial, promising findings.

Footnotes

Acknowledgements

The authors are very grateful to the volunteers who participated in this study, and the Guilan University of Medical Sciences, Rasht, Iran and Velayat Sub-Specialty Burn and Plastic Surgery Center.

Author contributions

M.M.R. and S.M. designed the overall study. M.M.R. designed the patient’s diet. S.P. and M.r.M. participated in the recruitment and data collection and also M.r.M. investigated wound healing. M.E.GH. analyzed the data. A.H. designed the web-site for the randomization to group and carried out data analysis. All authors read and approved the final manuscript.

Declaration of conflicting interests

Each author has made substantial contributions to the conception and design of the study or acquisition of data or analysis and interpretation of data, drafting the article or revising it critically for important intellectual content. Each author has seen and approved the contents of the submitted manuscript. None of the authors has any personal or financial conflicts of interest.

Funding

This research This study is part of a master’s thesis and receive grant from Guilan University of Medical Sciences.

Ethics approval

This study approved by ethics committee of Guilan University of Medical Sciences with the code number of IR.GUMS.REC.1400.303.

Informed consent

All patients provided written informed consents and All procedures were in accordance with the tenants of the Declaration of Helsinki and its later amendments.

Data Availability

The data and materials that support the findings of this study are available from the corresponding author upon reasonable request.

ORCID iDs

Sanaz Masoumi

Mohammadreza Mobayen

Abbreviation list

References

Smolle

Cambiaso-Daniel

Forbes

, et al. Recent trends in burn epidemiology worldwide: a systematic review. Burns 2017; 43(2): 249–257. DOI: 10.1016/j.burns.2016.08.013

Rousseau

A-F

Foidart-Desalle

Ledoux

, et al. Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: a one-year pilot randomized controlled trial in adults with severe burns. Burns 2015; 41(2): 317–325. DOI: 10.1016/j.burns.2014.07.005

Eitas

Stepp

Sjeklocha

, et al. Differential regulation of innate immune cytokine production through pharmacological activation of Nuclear Factor-Erythroid-2-Related Factor 2 (NRF2) in burn patient immune cells and monocytes. PloS One 2017; 12(9): e0184164. DOI: 10.1371/journal.pone

Mobayen

Zarei

Masoumi

, et al. Epidemiology of Childhood Burn: A 5-Year Retrospective Study in the Referral Burn Center of Northern Iran Northern Iran. Caspian Journal of Health Research 2021; 6(3): 101–108. DOI: 10.32598/CJHR.6.3.8

Magnotti

Deitch

. Burns, bacterial translocation, gut barrier function, and failure. J Burn Care Rehabil 2005; 26(5): 383–391. DOI: 10.1097/01.bcr.0000176878.79267.e8

Knackstedt

Gatherwright

. The role of thermal injury on intestinal bacterial translocation and the mitigating role of probiotics: A review of animal and human studies. Burns 2020; 46(5): 1005–1012. DOI: 10.16/j.burns.2019.07.007

Guarner

Malagelada

J-R

. Gut flora in health and disease. Lancet 2003; 361(9356): 512–519. DOI: 10.1016/S0140-6736(03)12489-0

Koren

Gurfinkel

Glezinger

, et al. The effect of Lactobacillus bacteria supplement on sepsis and its complications in patients with acute burns. Burns 2007; 33(5): 594–598. DOI: 10.1016/j.burns.2006.09.007

Petrof

Dhaliwal

Manzanares

, et al. Probiotics in the critically ill: a systematic review of the randomized trial evidence. Crit Care Med 2012; 40(12): 3290–3302. DOI: 10.1097/CCM.0b013e318260cc33

10.

Barraud

Bollaert

P-E

Gibot

. Impact of the administration of probiotics on mortality in critically ill adult patients: a meta-analysis of randomized controlled trials. Chest 2013; 143(3): 646–655. DOI: 10.1378/chest.12-745

11.

Putra

Pebrianton

Suharjono

, et al. editors. The Role of Probiotics in Inflammatory Responses of Critically-Ill Burn Patients (A Randomized Clinical Trial). Health Science International Conference (HSIC 2017); 2017: Atlantis Press.

12.

Jebur

. Therapeutic efficacy of Lactobacillus acidophilus against bacterial isolates from burn wounds. N Am J Med Sci 2010; 2(12): 586–591. DOI: 10.4297/najms.2010.586

13.

Eslami

Bahar

Keikha

, et al. Probiotics function and modulation of the immune system in allergic diseases. Allergol Immunopathol 2020; 48(6): 771–788. DOI: 10.1016/j.aller.2020.04.005

14.

Christensen

Frøkiær

Pestka

. Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. J Immunol 2002; 168(1): 171–178. DOI: 10.4049/jimmunol.168.1.171

15.

Oryan

Alemzadeh

Eskandari

. Kefir Accelerates Burn Wound Healing Through Inducing Fibroblast Cell Migration In Vitro and Modulating the Expression of IL-1ß, TGF-ß1, and bFGF Genes In Vivo. Probiotics Antimicrob Proteins 2019; 11(3): 874–886. DOI: 10.1007/s12602-018-9435-6

16.

Jamalifar

Rahimi

Samadi

, et al. Antimicrobial activity of different Lactobacillus species against multi-drug resistant clinical isolates of Pseudomonas aeruginosa. Iran J Microbiol 2011; 3(1): 21–25.

17.

Miller

Kaptchuk

. Sham procedures and the ethics of clinical trials. J R Soc Med 2004; 97(12): 576–578.

18.

El-Ghazely

Mahmoud

Atia

, et al. Effect of probiotic administration in the therapy of pediatric thermal burn. Ann Burns Fire Disasters 2016; 29(4): 268–272.

19.

Mayes

Gottschlich

James

, et al. Clinical safety and efficacy of probiotic administration following burn injury. J Burn Care Res 2015; 36(1): 92–99. DOI: 10.1097/BCR.0000000000000139

20.

Andersen

Brunicardi

. Schwartz's principles of surgery. McGraw-Hill, Medical Pub. Division, 2010.

21.

Marnell

Mold

Du Clos

. C-reactive protein: ligands, receptors and role in inflammation. Clin Immunol 2005; 117(2): 104–111. DOI: 10.1016/j.clim.2005.08.004

22.

Korkmaz

Krijnen

PAJ

Ulrich

MMW

, et al. The role of complement in the acute phase response after burns. Burns 2017; 43(7): 1390–1399. DOI: 10.016/j.burns.2017.03.007

23.

Pagana

. Mosby's manual of diagnostic and laboratory tests-e-book. USA: Elsevier Health Sciences, 2017.

24.

Sanaie

Ebrahimi-Mameghani

Hamishehkar

, et al. Effect of a multispecies probiotic on inflammatory markers in critically ill patients: A randomized, double-blind, placebo-controlled trial. J Res Med Sci 2014; 19(9): 827–833.

25.

McNaught

Woodcock

Anderson

ADG

, et al. A prospective randomised trial of probiotics in critically ill patients. Clin Nutr 2005; 24(2): 211–219. DOI: 10.1016/j.clnu.2004.08.008

26.

Alberda

Gramlich

Meddings

, et al. Effects of probiotic therapy in critically ill patients: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2007; 85(3): 816–823. DOI: 10.1093/ajcn/85.3.816

27.

Wang

Yao

Xiao

, et al. Bifidobacterial supplement enhances the expression and excretion of intestinal sIgA in severely burned rats. Zhonghua Wai Ke Za Zhi 2003; 41(5): 385–388.

28.

Tahir

Makhdoom

Awan

, et al. Role of probiotics in the management of burns patients. World J Med Sci 2014; 11(3): 417–421. DOI: 10.5829/idosi.wjms.2014.11.3.85244

Effect of probiotic administration in inflammatory responses of thermal burns

Abstract

Objectives & Introduction

Methods

Results

Conclusion

Keywords

Introduction

Methods

Participants

Randomization

Intervention

Data collection

Statistical analysis

Results

Discussion

Limitations

Conclusion

Footnotes

Acknowledgements

Author contributions

Declaration of conflicting interests

Funding

Ethics approval

Informed consent

Data Availability

ORCID iDs

Abbreviation list

References