Recent studies done with prevention or treatment of T2DM using prebiotics, probiotics or synbiotics.
Abstract
Prebiotics, probiotics and synbiotics are components that enhance human health by several mechanisms. Patients suffering from type II diabetes mellitus (T2DM) and colorectal cancer have seen benefits when treated with a prebiotic, probiotic or synbiotic therapy. These benefits include the improvement of their lipid profile, oxidative stress status, as well as the modulation of the inflammatory and immune responses. The associated benefits of prebiotic, probiotic or synbiotic functional foods have been studied, showing promising results into the prevention or control of diabetes and colorectal cancer. This novelty research provides new evidence that the use of functional foods along with medical therapy could be used to further enhance patient’s health.
Keywords
- prebiotics
- probiotics
- synbiotics
- T2DM
- colorectal cancer
1. Introduction
Prebiotics, probiotics and synbiotics provide several health benefits to its consumer, such as better control of the glycemic index, blood triglycerides (TG) reduction, prevention of cancer, improvement of mineral absorption, among others [1–3]. Prebiotics, probiotics and synbiotics have been added to food products in order to develop functional foods that confer additional health benefits besides the nutritional ones. Due to the health benefits they provide, the market for functional foods has increased in the previous years, growing up to a 47.6 billion US$, and it is expected to continue growing during the following years [4].
The objective of this chapter was to show some of the latest work done regarding the use of prebiotics, probiotics and synbiotics in prevention and treatment of type II diabetes mellitus (T2DM) and colorectal cancer, along with clinical studies showing that functional foods enriched with at least one of these components show a health benefit to patients.
2. Diabetes
Diabetes is a disease in which the body cannot regulate the amount of sugar in blood, being two major types of the disease:
Type I: there is little or none insulin production, and insulin injections are needed daily.
Type II: insulin resistance is present and glucose is unable to enter the cells to be used stored or used as energy.
Symptoms of both types include fatigue, blurry vision and slower healing in bladder and kidney infections. For type I, insulin injection is currently the only treatment, as for type II, medication is used when needed. These therapeutic drugs include α-glucosidase inhibitors, sulfonylureas, biguanides, among others. However, for most cases of T2DM, weight loss, healthy diet as well as exercise are enough to control or put into remission the disease [5]. Due to the nature of T2DM, this type poses a real possibility of overcoming the disease and where most of research is done in order to prevent, control and cure the disease.
The epidemics of diabetes is growing alarmingly, and it is estimated that by 2030, 342 million people (4.8% world’s population) will be suffering from this disease [6]. It is estimated that 4 million people die from its complications each year, costing around 3.9 billion US$ for Brazil, 0.8 billion US$ for Argentina, 2.0 billion US$ for Mexico, and up to 44 billion US$ for USA in 1994; in 2012, it was 245 billion US$ for USA [7,8].
2.1. T2DM prebiotic, probiotic and synbiotic clinical therapy
2.1.1. Proposed molecular mechanisms
The molecular mechanisms on how probiotics or prebiotics work is not fully understood yet; however, few proposed or suggested mechanisms have been presented. Since T2DM is at a higher risk of cardiovascular complications, improvement or control of the lipid profile associated with prebiotics and probiotics has been studied, and it has been suggested that this improvement is done by the production of short-chain fatty acids (SCFA), which act as inhibitors of lipid synthesis in liver [9].
Probiotics have also shown the ability to reduce reactive oxygen species (ROS) which, among other harmful effects, damage the intestinal barrier and allow bacterial translocation, which might lead to different infections and inflammation.
Another proposed mechanism is that probiotics have the ability to modulate Th1 and Th2 pro-inflammatory responses, aiding in prevention of development of T2DM. Probiotic regulation of expression of
Moving on to prebiotics, inulin, the most widely studied prebiotic, has shown the effect of glycemic index control by reducing the absorption rate of glucose and lipid profile control by decreasing the amount of serum triglycerides through the inhibition of glycerol-3-phosphate acyltransferase and fatty acid synthase as well as key enzymes in
Extensive work has been done regarding the study of molecular mechanisms in which both prebiotics and probiotics function. Still, further studies are needed in order to establish a better understanding of the molecular mechanisms in which both enhance human health.
2.1.2. Recent studies done with T2DM
Several studies had been made with the use of prebiotics, probiotics or synbiotics into the treatment of T2DM. One of the first most recent studies uses probiotics as an aid in the treatment in diabetic rats along with gliclazide, an antidiabetic drug. Forty rats were divided into four groups: healthy, healthy probiotic, diabetic and diabetic probiotic. In the last two, diabetes was induced by alloxan solution injection (30 mg/kg). A mixture of
A different study used oligofructose-enriched inulin in order to evaluate the effect on several T2DM markers such as triglycerides (TG), total cholesterol (TC), malondialdehyde (MDA), low-density lipoprotein cholesterol (LDL-C), among others. A randomized, triple-blind, placebo-controlled trail was conducted for 8 weeks in 70 diabetic female volunteers whose ages range from 25 to 65 years old and having diabetes diagnosed for more than 6 months; however, only 52 patients completed the study. Maltodextrin was used as placebo in the control group, while the oligofructose-enriched inulin for the intervention group, both doses consisted of 5 g of supplement to be eaten during breakfast and 5 g at dinner. An Analysis of Covariance (ANCOVA) was performed to identify differences between the two groups. Results show that there was a general decrease in lipid levels, such as TC, from 203.1 mg/dL to 175 mg/dL, and LDL-C from 116.3 mg/dL to 94.3 mg/dL. There was no significant decrease in TG, from 216.8 mg/dL to 176.9 mg/dL, nor in MDA which values ranged from 4.3 nmol/mL to 2.6 nmol/mL [14]. This study suggests that these prebiotics have potential in improving the lipid profile of patients with T2DM, and this would lead to a decrease in the cardiovascular risk associated with the disease.
Impaired glucose tolerance is a major risk factor involved in T2DM, and a study was made assessing the effect of a probiotic in a preventive and/or ameliorating way in male Sprague Dawley rats.
As mentioned earlier, it is suggested that lipid profile and oxidative stress are improved by probiotics. A single-blinded clinical trial was performed with 40 T2DM patients studying the effect of probiotics
Further studies have been done in the topic of T2DM; however, there is no an extensive amount of literature available. A short summary of these is presented in Table 1.
Authors | Component | Host | Dosage/ length |
Study’s design |
---|---|---|---|---|
[16]* | Several and strains |
T2DM patients | 4 g sachets daily intake (2.5 × 109 CFU/g) 26 weeks |
Single-center, double-blinded, randomized, placebo-controlled study with 60 patients |
[11] | Sprague Dawley Rats |
4 × 109 CFU/d rat 2 weeks |
1. Sixteen rats divided into high-fat fructose diet (HFS) and normal control (NC) 2. Twenty-seven rats divided into three groups: HSF, NC, and HSF with probiotics ANOVA followed by LSD |
|
[17]* | Inulin oligofructose |
Pre- diabetic patients |
10 g daily 6.5 months |
Randomized crossover controlled trial Kolmogorov–Smirnov goodness-of-fit test, Pearson correlation, and ANOVA |
[18] | Several and strains |
T2DM patients | Range from 1.5 × 109 to 7 × 109 CFU 15 months |
Randomized double-blinded controlled clinical trial Kolmogorov–Smirnov test, Paired sample Student’s |
[19]* | Inulin | Pre- diabetic patients |
10 g inulin daily 6 weeks |
Double-blinded, placebo-controlled, parallel group design Multiple-sample repeated- measures analysis of variance, ANCOVA |
[20] | T2DM patients | 109 CFU/day 7 months |
Randomized double-blinded parallel group placebo-controlled trial Shapiro–Wilk test, Student’s |
|
[21] | Polydextrose Antidiabetic drugs |
Mice | 109 CFU Polydextrose 0.25 g/day 4 weeks |
1. Forty mice divided into four groups: diabetic control, metformin + B420 2. Forty-eight mice divided into six groups: non- diabetic control, diabetic control, sitagliptin (SITA), SITA + polydextrose (PD), SITA + B420, SITA + PD + B420 2 × 2 Factorial, Shapiro–Wilk, ANOVA, Tukey’s HSD |
2.2. Functional foods in T2DM
As mentioned above, T2DM can be controlled by a healthy diet. This has been used as a novelty approach into the treatment of the disease using prebiotic, probiotic or synbiotic functional foods, while evaluating the health benefits provided. Most of the functional foods studied are either yoghurts or breads.
A probiotic yogurt with
One year later, results from another similar study were published in which a probiotic yogurt containing
On another study, the evaluation of the lipid profile of T2DM patients while consuming a synbiotic bread containing
On a different approach,
In a different study, another synbiotic functional food was developed enriched with β-carotene, and this food contained inulin as a prebiotic and
To conclude with T2DM and functional foods, another synbiotic bread was developed using
3. Colorectal cancer
As any other cancer, colorectal is characterized by uncontrolled proliferation of cells which lead to the formation of tumors. Symptoms involve blood in stool, either diarrhea or constipation, fatigue, frequent gas pain cramps, among others. Colorectal cancer is the third most common cancer worldwide in men, just below lung and prostate cancers, and second most common in women just below breast cancer. There were 1.3 million new diagnosed cases of colorectal cancer in 2012 and it is expected that this figure will keep growing [28].
The cost of colorectal cancer in 2010 in the US was of 14.14 billion US$, while worldwide it is estimated to be of 99 billion US$ annually [29, 30].
3.1. Colorectal cancer prebiotic, probiotic and synbiotic clinical therapy
3.1.1. Proposed molecular mechanisms
Several molecular mechanisms in which probiotics and prebiotics work and help prevent as well as ameliorate health in colorectal cancer patients have been proposed, some are presented here. Probiotics cause the acidification of pH which has been shown to inhibit
Most of the studies done on the mechanism of prebiotics have been on oligofructose prebiotics such fructooligosaccharides and inulin. Oligofructose-enriched inulin has shown a decrease in the expression of enzymes linked to colorectal cancer such as glutathione S-transferase and nitric oxide synthase. Also, cyclooxygenase 2, an enzyme upregulated in cancers was in lower in prebiotic rats than in control rats. Fermentation in colon generates SCFA, butyrate being one of them. Sodium butyrate has been found to be a grown inhibitor and inducer of phenotype differentiation and apoptosis, reducing the risk factors of developing cancer [31].
While there are several proposed mechanisms with evidence suggesting them, for both probiotics and prebiotics, further studies must be done in order to provide uncontroversial evidence on the established pathways and provide better understanding of the molecular dynamics followed in the human colon.
3.1.2. Recent studies done with colorectal cancer
Several studies have been made in order to evaluate the effect on several variables associated with colorectal cancer. In a randomized double-blinded placebo-controlled trial, a synbiotic treatment containing
A different approach has also been taken, and
Fructans and soybean meal (SM) were used to evaluate the effect on tumors. Some of the variables measured in colorectal cancer-induced rats with azoxymethane were GST activity and bacterial enzyme activity. Ninety Fisher 344 male rats were randomly assigned to nine groups, which difference was the diet. Control groups rats were fed with American Institute of Nutrition-93 Growth/Maintenance (AIN-93G/M) diet, and the eight groups were fed with the following diets: prebiotics 5%, prebiotics 10%, SM 5%, SM 10%, prebiotics 5% + SM 5%, 10% + SM 10%, 5% + SM 10% and 10% + SM 5%. Tumors present in control group were bigger in size than those fed with either fructans, soybean meal or both. GST activity was increased in two- to fourfold in rats fed with treatment diets compared to the control group, and β-glucosidase activity showed no significant difference between control group and treatment one, with the exception of a significant increase in rats fed with prebiotics 10% and rats fed with prebiotics and SM 10% + 5%. Overall there were better results obtained in prebiotics + SM consumption [34]. These results suggest that prebiotics can be used in treatment of colorectal cancer.
The effect of inulin and lactulose on procarcinogenic biomarkers in 1,2-dimethylhydrazine dihydrochloride (DMH)-induced rats has also been evaluated. Thirty-two male Sprague Dawley rats were divided into four groups: group I which is the control group received a single dose of EDTA saline solution per week, group II received a single dose of DMH per week, group III received a single dose of DMH + inulin 10 mg/0.1 mL and Group IV received DMH + lactulose 14 mg/0.1 mL. All doses were given during the course of 6 weeks. For groups III and IV, prebiotics were administered orally daily and on the 8th day, a single dose of DMH was administered. Three variables were measured among others, and these are as follows: nitroreductase, β-glucosidase and β-glucuronidase activities. Statistical analysis was done using one-way ANOVA and a post hoc LSD tests. Activity of β-glucuronidase (0.045 ± 0.006 µg/h/mg) and β-glucosidase (1.007 ± 0.115 µg/h/mg) was found to be decreased in the inulin + DMH group when compared to control (0.243 ± 0.059 µg/h/mg and 2.219 ± 0.745 µg/h/mg, respectively). Nitroreductase activity was increased in inulin + DMH (0.045 ± 0.005 µg/h/mg) compared to control (0.0162 ± 0.005 µg/h/mg) [36]. These results also suggest the colorectal cancer protection properties of inulin, which could be used in the prevention of developing colorectal cancer.
On similar study, thirty male and female Sprague Dawley rats were divided into three groups: a control group fed only with conventional feed, a DMH group and a DMH + inulin fed group. DMH and DMH + inulin group were treated with DMH at a dose of 21 mg/kg five times in weekly intervals, and DMH + inulin rats were fed with a dose of 80 g/kg of conventional feed during 28 weeks. For statistical analysis of the variables evaluated, a one-way ANOVA test was used. It was found that activity of β-glucuronidase decreased as well as the number of COX-2- and NFκB-positive cells along with a decrease in the expression of IL-2, TNF-α and IL-10. Moreover, there was a significant decrease in β-glucosidase activity (0.03 ± 0.02 µmol/min/g) when compared to the control group (0.08 ± 0.02 µmol/min/g), and also there was a significant decrease in coliforms (5.96 ± 0.22 log10 CFU/g) when compared to control (6.17 ± 0.56 log10 CFU/g) and DMH group 6.34 ± 0.25 log10 CFU/g). This decrease in coliforms explains the reduction in β-glucuronidase activity. Butyric and propionic acid levels were higher in DMH + inulin group, and these short-chain fatty acids have been associated with apoptosis and metastasis, carcinogen reduction, among others [37].
Several other studies have been made, and these are shown along with a brief summary of each in Table 2.
Authors | Component | Organism/cell line |
Dosage/length | Study’s design |
---|---|---|---|---|
[38] | fermentation supernatant |
Colon cancer SW620 |
Several protein concentrations ranging from 0 up to 0.75 mg/mL 24 h |
Supernatant was incubated with SW620 cells and evaluated in viability essays Statistical analysis were done using one- way ANOVA and Bonferroni’s multiple comparison test |
[39] | supernatants |
Caco-2 HT-29 |
2.5, 5 and 10 mg/mL 48 h |
Probiotic fermented medium Supernatants was incubated with cancer cells and evaluated viability Statistical data were analyzed using one-way ANOVA |
[40] | C57BL/6 mice | 1 × 108 CFU 10 weeks |
Mice were administered probiotic and DMH, intestinal damage evaluation, cytokine analysis, gene expression analysis Bonferroni’s multiple comparison test |
|
[41] | Xylooligo saccharides (XOS) |
Wistar rats | 5% and 10% XOS 45 days |
XOS diet in rats, bacterial analysis y cecal matter, biochemical assays, proliferation markers One-way ANOVA |
[42] | HT-29 | 0, 10, 50, 100, MOI 48 h |
Calculation of multiplicity of infection (MOI), analysis cell distribution, RNA extraction, and semiquantitative RT-PCR One-way ANOVA and Duncan’s post hoc tests |
3.2. Functional foods in colorectal cancer
To the best of our knowledge, only a couple of studies have been made regarding prebiotic, probiotic or synbiotic functional foods for prevention, control or treatment of colorectal cancer.
A synbiotic food using oligofructose-enriched inulin and
A study was done on 56 F344 rats using a probiotic fermented milk with
4. Conclusions and perspectives
The effect of prebiotics, probiotics and synbiotics over several health markers in T2DM and colorectal cancer patients has been shown through several studies discussed in this chapter. Some of the health benefits presented in this chapter for T2DM are the improvement of lipid and glycemic profile, increase in blood insulin concentration and modulation on the inflammatory response. For colorectal cancer, some of the health benefits presented in this chapter are the modulation of the immune response, antitumor activity and tumor size reduction. However, further research is needed in order to understand completely the specific molecular pathway of each component has.
The use of functional foods for prevention and control of T2DM is a promising opportunity which must be taken into account, after all, and one of the most common causes of this disease is obesity and poor diet. The design of functional foods with prebiotics, probiotics or synbiotics that will help enhance T2DM patient’s health would be an aid in the fight against it; however, the elimination or substitution of antidiabetic drugs is not recommended or endorsed.
There is much to do in the research of prebiotic, probiotic or synbiotic functional foods for the prevention, control or treatment of colorectal cancer. There is evidence suggesting that therapy enhances patient’s health, and this should encourage further research into the development of functional foods and their clinical studies in patients. If successful results during the following years are obtained, this could provide as an aid in the fight against colorectal cancer.
The use of functional foods should be used with caution and as a support to clinical therapy, not exclusively as an alternative. This combination could lead to further improvement in patient’s health as some studies have found synergistic effect of probiotics along with medical drugs.
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