Evaluation Regarding the Efficacy and Safety of a Probiotic Mixture in Healthy Volunteers with Evacuation Disorders

Lourdes Rodríguez-Fragoso, Adriana Sandoval-Ocampo, Martha Corbalá-Nava, Carlos A. Arjona-Canul, Diana Lizbeth Gomez-Galicia, Guillermo Tellez, Billy Hargis, Jorge Reyes-Esparza

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DOI: 10.4236/fns.2012.31017                

Abstract

Probiotics have been used in humans for almost a century and are widely recommended because they play an important role in gastrointestinal physiological and pathophysiological processes. The aim of this study was to evaluate the effi- cacy and safety of a probiotic mixture in healthy volunteers with evacuation disorders. We undertook a prospective study with historical control. We used the number of evacuations, effort and stool consistency 10 days before, 10 days during and 10 days after treatment with the probiotic as primary outcome measures. Eligible par-ticipants comprised 25 patients with an average age of 25.12 years (range: 18 - 55) who suffered from evacuation disorders. BIO L6 is a func- tional food consisting of a probiotic preparation that contains 1 mg (108 CFUs) of lyophilized strains of Lactic Acid Bacteria resuspended in 250 mL of drinking water. The probiotic preparation was prescribed daily for two weeks, five days a week. A significant increase in the number of evacuations was observed in 23 patients during BIO L6 consump- tion and continued in 20 after consumption. The degree of effort spent defecating decreased in 17 patients during treat- ment and in 7 after treatment. A significant improvement (P < 0.001) in stool consistency was also observed in all pa- tients receiving BIO L6. Fourteen patients had at least one adverse event (AE) for one or two days during treatment; most treatment-related AEs were considered minor or mild in terms of severity and were consistent with AEs reported for probiotic consumption. The results of this study suggest that the use of probiotic mixture BIO L6 is effective, safe and tolerable and provides beneficial effects for subjects with evacuations disorders.

Keywords

Chronic Constipation; Probiotic; Lactic Acid Bacteria

1. Introduction

The gastrointestinal tract is a complex ecosystem that hosts a diverse and highly evolved microbial community composed of hundreds of different microbial species [1]. The interactions between this complex community and the human host have become the focus of scientific research due to an increase in the incidence of illnesses related to deficient or compromised microflora (e.g., gastrointestinal tract infections, inflammatory bowel disease, irritable bowel syndrome, antibiotic-induced diarrhea, constipation, food allergies, cardiovascular disease, and certain cancers) [2]. The importance of intestinal microflora composition in physiological and pathophysiological processes in the gastrointestinal tract (GIT) has become increasingly evident and led to new preventive and therapeutic options [3-5]. It has been documented that primary motility disturbances can induce changes in intestinal microflora content and thereby further disturb intestinal physiology (and vice versa) [6].

Probiotics have been used in humans for almost a century and are widely recommended for the treatment of a variety of ills assumed to be of colonic origin, including diarrhea, constipation, bloating, and flatulence [7]. Probiotics may have potential beneficial effects in several gastroenteric conditions, especially when the intestinal flora has been disturbed [8]. New discoveries are specifically related to the beneficial effects of Lactic Acid Bacteria (LAB). It is possible to increase the proportion of LAB in the gastrointestinal microflora through probiotic consumption or oral administration of specific nondigestible substrates such as oligofructose [9]. Nowadays, there is a growing interest in the use of probiotics as a safe way of changing the intestinal microflora to treat gastrointestinal diseases and, particularly, for modulating intestinal transit [10].

Evacuation disorders and hard feces are common in industrialized countries, affecting an average of 12% to 17% of the healthy adult population of any age [11]. Constipation not only interferes with quality of life, it also often ranks as a syndrome requiring competent medical intervention. Constipation relief is often mentioned as a potential health benefit of probiotics [8]. However, there have been relatively few studies in this field and the results have been conflicting. Some noted an increase in the number of stools and a reduction of symptoms in adult patients with chronic constipation, while others observed no improvement [12-16]. The effect of LAB ingestion on orofecal gut transit time appears to be dependent on the specific bacterial strain(s) used and the population being studied. Different probiotic strains might perform differently when treating constipation. The aim of this study was to evaluate the efficacy and safety of a probiotic mixture in healthy volunteers with evacuations disorders.

2. Materials and Methods

2.1. Study Design

This was a prospective study with historical control conducted on 25 healthy volunteers suffering evacuation disorders. Volunteers were students and workers from the College of Pharmacy at the Universidad Autónoma del Estado de Morelos in Cuernavaca, Morelos (Mexico). Subjects were enrolled after a complete physical examination, normal value of laboratory tests, and no evidence of gastrointestinal disease at plain abdomen x-ray and ultrasound studies. Exclusion criteria were: constipation caused by enteric neuromuscular, anatomic, or metabolic diseases (as established by medical history, an abnormal thyroid hormone level, or prior anorectal manometry, barium, or ionogram examination); clinical signs of coexisting acute systemic illnesses; underlying severe chronic diseases; food allergies or other chronic gastrointestinal diseases; use of probiotics (yogurt) and prebiotics in the previous two weeks, or use of antibiotics or some medication in the previous week. Constipation was defined as fewer than 1 evacuation per day and/or presence of effort during bowel evacuation.

The protocol was approved by the Institutional Review Board of the College of Pharmacy. The study was performed in accordance with the Declaration of Helsinki and amendments relevant to biomedical research involveing human subjects, and the principles of the Guideline for Good Clinical Practice [17,18]. All eligible volunteers were informed of the aim and risks of the study by the clinical researchers and provided written informed consent before enrollment.

2.2. Administration of Probiotic

BIO L6^® is a functional food consisting of 10⁸ CFUs of lyophilized LAB strains in 10 g of a powder that is diluted in 250 mL of water. The probiotic formulations were manufactured and provided by Health-Tech-SigrahZellet S.A. de C.V. (Mexico). Each formulation was analyzed for the number of viable cells and absence of microbiologic contaminants. The genotypic 16S rRNA identification of the organisms used in the present study for the probiotic culture is summarized in Table 1.

Each dose was taken upon awakening and diluted in 250 mL of water. Subjects ingested the probiotic five times a week for two weeks. The treatment was stopped if subjects presented severe side effects or toxicity; e.g., acute diarrhea or fever. If patients presented moderate side effects, the dose was reduced.

2.3. Evaluations

Upon enrollment, subjects were asked to record each parameter in a specific case report form throughout the week before each visit: T₀: ten days before the beginning of treatment; T₁₀: ten days during treatment; and T₂₀: ten days after treatment. In addition to the case report forms, the subjects’ general condition and vital status were assessed during each visit. The parameters recorded in the forms were: frequency (number of daily evacuations); ease of expulsion; consistency of feces; flatulence; colic or pain.

Although determining the number of defecations was simple and direct, the other parameters were noted and recorded using the easiest method for the subject, that is, identifying the lowest value with 0 or 1, the mid-range

Table 1. Lactic acid bacteria contained in Bio L6^® probiotic.

with 2 and the highest one with 3. The value scale was explained and agreed upon with the volunteers as follows:

1) Number of daily evacuations (<1 y > 1).

2) Effort during expulsion: 1, without effort; 2, effort without pain; 3, effort with pain.

3) Consistency of feces: 1, hard; 2, soft; 3, semi-liquid.

4) Flatulence: 0, none; 1, little; 2, regular; 3, abundant.

5) Pain, colic: 0, no pain; 1, light pain; 2, medium pain; 3, intense pain.

2.4. Primary and Secondary Endpoints

The primary efficacy endpoint was the number of evacuations in 24 h. The secondary efficacy end points were ease of expulsion during defecation and feces consistency during the treatment with the probiotic. All data were prospectively obtained from two questionnaires and registered onto a structured database. Adherence to treatment was monitored through interviews with each patient and the delivery of empty bottles. Subjects who voluntarily discontinued the treatment or forgot to take powder formulations for at least 3 days were considered dropouts.

Probiotics colonization was probed by taking a stool culture of lactobacillus from each patient previous to treatment and in the last day of treatment. The assay allowed us to morphologically characterize the presence of LAB colonies before and after treatment.

2.5. Statistical Analysis

The number of daily defecations is expressed as mean ± SD. The number of evacuations was compared by one way analysis of variance using the GLM procedure of SAS with significance reported as P < 0.05. The chisquared test of independence was used to determine significant differences (P < 0.001) in presence or absence of constipation and feces consistency before and after treatment.

3. Results

3.1. Evaluation of Efficacy

A total of 30 healthy volunteers were identified. Out of these, 25 subjects (17 females and 8 males) were selected for the present study according to inclusion criteria. One subject withdrew prematurely from treatment because it increased her constipation. 24 healthy volunteers finished the study. The average age was 25.5 years (range 18 - 55 years) and a total of 23 subjects showed some degree of improvement.

Table 2 shows the effect of probiotic Bio L6^® on the number of daily evacuations. As we can see, 23 subjects had an increase in evacuation frequency during treatment (p < 0.001) (Table 3) and 20 subjects continued to experience increased frequency in excretion 10 days after they had finished treatment (p < 0.001) (Table 3).

Conflicts of Interest

The authors declare no conflicts of interest.

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