A Guide to Probiotics and Health1
The World Health Organization (WHO) defines probiotics as "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host" (Hill et al. 2014). In the United States, probiotics are considered dietary supplements, not food or drugs, and thus are not specifically regulated by the Food and Drug Administration (FDA). As dietary supplements, some products containing live microorganisms have been marketed as probiotics without having undergone the testing needed to confirm their health benefits. It is recommended that only microbial species that have been shown to confer health benefits in well-designed, controlled studies should be considered probiotics (Hill et al. 2014). Live cultures that are used in the fermentation of foods (e.g., yogurt) and that have no demonstrated health benefits are not considered probiotics.
Probiotics are beneficial for gastrointestinal wellness, immunity, and a variety of other health outcomes (Sanchez et al. 2016). There are many probiotic supplements available in the marketplace and choosing a supplement can be challenging. This review provides a summary of the health benefits of probiotics that are backed by high levels of scientific evidence.
Many bacteria and other microorganisms have been tested for their beneficial effects on health. It is important to note that these microorganisms may differ in their health effects, so each potential probiotic needs to be tested to determine if it exerts a specific health benefit. Research carried out in animals alone cannot be used to support recommendations for humans. Human research studies need to be completed on all potential probiotics. Furthermore, a positive health effect from a single human research study is not sufficient to confirm the health benefit of a probiotic. A number of well-designed studies demonstrating similar positive findings provide the strongest evidence that a probiotic is effective.
A high level of scientific evidence is considered to be a systematic review with meta-analysis. A systematic review is a structured search and review of all studies to date examining a specific health benefit of a probiotic. In health research, it is common to pool and statistically analyze the results of studies, a technique known as meta-analysis. Positive findings of a systematic review with meta-analysis strongly suggests efficacy, i.e., the probiotic exerts a specific health benefit. It has been suggested that systematic reviews should be conducted on studies of a single species (McFarland 2016), although most reviews to date have combined different species. Many of the health benefits of probiotics described in this review have this strong level of scientific evidence. However, it is important to note that there are many more strains that may be effective but have yet to be studied.
Health Benefits of Probiotics
Probiotics differ in their effects on human health. Most probiotics are from the genera Bifidobacterium or Lactobacillus. Various species of Bifidobacterium (B. adolescentis, B. animalis, B. bifidum, B. breve, and B. longum) and Lactobacillus (L.acidophilus, L. casei, L. fermentum, L. gasseri, L. johnsonii, L. paracasei, L. plantarum, and L. rhamnosus) provide general health benefits (Health Canada 2009). The dose of the probiotic taken, measured in "colony forming units", or CFUs, is important for effectiveness. A minimum dose of 1 × 109 (1 billion) CFUs per serving is thought to be needed to provide general health benefits (Health Canada 2009).
Probiotics exert health benefits by a number of mechanisms. Most probiotics inhibit the growth of pathogens and produce beneficial fermentation products such as short-chain fatty acids (Hill et al. 2014, Oelschlaeger 2010). Many probiotic species produce vitamins and useful enzymes and help to maintain gut health. A few probiotic strains have immune, neurological, or other body system effects, and some probiotic strains are considered drugs because they have been shown to prevent or treat disease (McFarland, Evans, and Goldstein 2018).
One common gastrointestinal condition is constipation. Those suffering from constipation often complain of infrequent, hard stools that are difficult to pass. A lack of dietary fiber, medical conditions, and certain medications are common causes of constipation.
One of the main functions of the colon is the removal of water. This is important for the prevention of diarrhea. However, the longer material remains in the colon, the more water is removed. If the time spent in the colon is lengthy, the result may be constipation. Transit time is the time it takes for the contents of the gastrointestinal tract to move through the body. Most of this time is spent in the colon. When transit time is slow, lasting many days, the result is hard stools that are difficult to pass. A stool form or consistency rating is a useful indicator of transit time (hard stools = slow transit; soft stools = normal transit; liquid stools = fast transit).
Probiotics are effective in speeding up transit time in adults and are most effective in people with constipation (Dimidi et al. 2014; Miller, Zimmermann, and Ouwehand 2016; Zhang et al. 2020). Stool consistency responds to changes in transit time and may improve with certain probiotics. A systematic review supports that probiotics, specifically multistrain probiotics, significantly improved stool consistency (stools became softer) and stool frequency (Zhang et al. 2020). In contrast, a previous review, including different studies, provided some evidence that single-strain probiotics may be more effective than the multistrain probiotics (Dimidi et al. 2014). There is also conflicting evidence regarding the effectiveness of Bifidobacterium lactis (B. lactis) strains on constipation outcomes (Zhang et al. 2020; Dimidi et al. 2014), and thus more research is needed.
Diarrhea is commonly defined as frequent loose or watery stools and is often caused by pathogens. Potential probiotics have been evaluated in many studies to determine if they are effective in preventing various types of diarrhea in adults, including antibiotic-associated diarrhea and chemotherapy-induced diarrhea. Clostridium difficile diarrhea is the most common antibiotic-associated diarrhea.
Evidence from a systematic review and meta-analysis supports that probiotics reduce the incidence of Clostridium difficile-associated diarrhea and other antibiotic-associated diarrheas, with Lactobacillus casei being the most effective (Ma et al. 2020). Also, duration of diarrhea and the time until onset of diarrhea improved with various probiotics (Ma et al. 2020). A previous review of trials using Lactobacillus spp., Saccharomyces spp., and combinations of probiotics also showed reduced risk for diarrhea (Lau and Chamberlain 2016). However, a meta-analysis, which separated participants by age, found that probiotic administration did not reduce the risk of antibiotic-associated diarrhea in adults over 65 years of age (Jafarnejad et al. 2016).
Meta-analyses have also been carried out on specific strains of probiotics and their efficacy in antibiotic-associated diarrhea. Lactobacillus rhamnosus GG, Lactobacillus casei, Bacillus clausii, Saccharomyces boulardii, Lactobacillus acidophilus, and Multi-genera II are more effective than placebo in helping to prevent antibiotic-associated diarrhea (Cai et al. 2018). Lactobacillus rhamnosus GG is effective in decreasing risk of antibiotic-associated diarrhea in children, but in adults, Lactobacillus rhamnosus GG effective was only in those receiving antibiotics for H. pylori eradication (see section below) (Szajewska and Kolodziej 2015a). Saccharomyces boulardii is effective in decreasing risk of antibiotic-associated diarrhea in adults, but not specifically Clostridium difficile-associated diarrhea (Szajewska and Kolodziej 2015b).
A meta-analysis has shown that probiotics decrease radiotherapy-induced diarrhea but not chemotherapy-induced diarrhea in patients with abdominal and pelvic cancer (Wang et al. 2016). However, a newer meta-analysis showed that the application of probiotics before or during chemotherapy effectively prevented the occurrence of chemotherapy-induced diarrhea among cancer patients (Lu et al. 2019).
Irritable Bowel Syndrome (IBS)
Irritable Bowel Syndrome (IBS) is a condition of the intestinal tract that results in abdominal pain and/or discomfort with altered bowel habits (diarrhea and/or constipation).
A systematic review using the medical diagnostic criteria of IBS (Rome III) showed that probiotics improved overall symptom scores and quality of life in individuals with IBS (Zhang, Li, et al. 2016). Probiotic doses of <1010 CFU and single strain probiotics may be more effective than multistrain formulations for symptom relief. Specifically, Lactobacillus acidophilus-SDC, Lactobacillus plantarum 299v, Bacillus coagulans, and Bifidobacterium bifidum MIMBb75 improved overall symptom scores in patients with IBS, and Bifidobacterium bifidum MIMBb7 improved quality of life. A more recent systematic review and meta-analysis of studies using Rome I, II, or III to diagnose individuals with IBS found that probiotics significantly improved overall IBS symptoms (Asha and Khalil 2020). However, the meta-analysis showed no differences in abdominal pain scores with probiotics in general compared to placebos, but abdominal pain scores were reduced with probiotics containing Lactobacillus spp.
H. pylori Infection and Peptic Ulcer Disease
Infection with Helicobacter pylori (H. pylori), a bacterial pathogen, causes gastritis (inflammation of the stomach lining) and, if left untreated, may lead to gastric ulcers and cancer. The current recommended treatment for H. pylori is a combination of antibiotics with a proton-pump inhibitor (stomach acid-reducing medication) (Li et al. 2015). However, the treatment may cause nausea, vomiting, and diarrhea.
Various probiotic mixtures have been evaluated for their efficacy for improving the treatment (eradication rates) of H. pylori infection and preventing side effects from treatment (Lu, Yu, et al. 2016; McFarland et al. 2016; Lv et al. 2015; Zhang et al. 2015; Gong, Li, and Sun 2015). In a meta-analysis examining 40 controlled trials, probiotics improved the eradication rate and decreased the side effects when added to the antibiotic treatments designed to eradicate H. pylori, especially when used before and during the eradication treatment and for more than 2 weeks (Shi et al. 2019). Compared with a control group, Lactobacillus spp., Saccharomyces spp., and multiple strains demonstrated significant improvements in eradication rates. Other strains may be effective, but more research is needed.
Diverticular disease is a common gastrointestinal disease, especially in older adults. Many older adults have diverticulosis (colonic diverticula, i.e., outpouching of the colon) but are without symptoms. Others develop symptoms such as abdominal pain, discomfort, and changes in bowel habit. A minority of individuals with diverticulosis develop diverticulitis, an acute inflammation of the diverticula.
There have been very few quality studies evaluating the effect of probiotics on diverticular disease (Lahner et al. 2016). Probiotics may potentially be beneficial in the management of symptoms of diverticular disease; however, much more research is needed before recommendations can be made.
Although probiotics are most often associated with gastrointestinal health, they may also have systemic effects, including an influence on body weight. In a recent review with meta-analysis multistrain and single-strain probiotics were reduced body weight, body mass index, waist circumference, fat mass, and fat percentage (Wang et al. 2019). The effects were stronger with high dose and single-strain probiotics. Similar findings were confirmed by an second review (Koutnikova et al. 2019). Currently, no specific recommendations can be made regarding the best strain combination and dose for body weight reduction.
Type 2 Diabetes
The goal of successful management of type 2 diabetes is to achieve near-normal fasting blood glucose and hemoglobin A1c, a blood test used to estimate average blood glucose levels over a three-month period. In three reviews of studies evaluating probiotics in participants with type 2 diabetes, fasting blood glucose was lower with probiotic supplementation compared to the placebo (Samah et al. 2016; Zhang, Wu, and Fei 2016; Li et al. 2016). The reviews differed on their findings with respect to probiotics and A1c, with one study showing a lowering and two showing no effect. However, the studies included were only four to eight weeks in length—too short to expect changes in A1c. In a more recent review of studies and meta-analysis evaluating the effect of oral intake of probiotics on variables related to obesity, diabetes, and nonalcoholic fatty liver disease, it was found that probiotics reduced fasting glucose, glycated hemoglobin, and insulin (Koutnikova et al. 2019). These improvements were observed with mixtures containing Bifidobacterium breve, Bifidobacterium longum, Streptococcus salivarius subsp. thermophilus, Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus delbrueckii.
Elevated serum total cholesterol and LDL (low-density lipoprotein) cholesterol are risk factors for cardiovascular disease. Consumption of probiotics has been found to significantly decrease total and LDL cholesterol (Cho and Kim 2015). Probiotics had no effect on HDL (high-density lipoprotein) cholesterol or triglycerides. Lactobacillus acidophilus alone and in combination with L. lactis and L. plantarum showed independent beneficial effects. As with other cholesterol trials, participants with the highest cholesterol levels showed the greatest benefits. A more recent review of studies concluded that administration of probiotics resulted in significant reductions of total cholesterol, LDL cholesterol, and triglycerides and increased HDL cholesterol (Tenorio-Jiménez et al. 2020). However, some of the studies evaluated used the probiotics in combination with other compounds, which makes it more difficult to determine the specific effects of the probiotics.
Urinary Tract Infections
The effects of a variety of strains, formulations, and doses of probiotics on the prevention of urinary tract infections in healthy individuals have been evaluated (Schwenger, Tejani, and Loewen 2015). No benefit was found, but most studies were small and of poor quality. More research is needed to determine if there is a relationship between probiotic consumption and urinary tract infections.
Upper respiratory tract infections (URTI), such as the common cold, are often due to viruses. For a number of years, meta-analysis evidence has supported the role of oral intake of probiotics and potential probiotics in decreasing the incidence of acute URTI, the duration of URTI, and related antibiotic use (Hao, Dong, and Wu 2015). However, confirmatory research studies of improved quality are needed. A review of studies and meta-analysis using several probiotic formulations, including those containing Lactobacillus and Bifidobacterium spp., found that infants and children who received probiotics to prevent acute illnesses had a lower risk of being prescribed antibiotics, compared to those who received a placebo (King et al. 2018).
Probiotics may be beneficial in the prevention and treatment of dental caries and periodontal disease. However, a recent systematic review showed that four studies found benefits of using probiotics as an adjunctive therapy in chronic periodontitis, whereas three studies found no benefits compared to placebo (Ikram et al. 2018). Probiotics, Bifidobacterium spp. in particular, have been shown to reduce populations of Streptococcus mutans, a bacteria linked to dental caries, and also may help manage gingivitis and periodontitis (Gruner, Paris, and Schwendicke 2016).
Probiotic Purchasing Tips
Although more research is needed to determine the health effects of many potential probiotics, it is wise to select a probiotic that has been well studied and has known health benefits. When choosing a probiotic, ensure that the probiotic is described by genus, species, and strain on the label (see Figure 1 below). When making a purchasing decision, look for information on the genus and species and the health benefit you are seeking. If the health effect is strain-specific, look for the strain (named by genus, species, and strain number) information. The label should clearly indicate the number of viable cells (CFUs), which should exceed, at a minimum, 1 × 109 (1 billion). Follow the manufacturer's recommendation for storage because some probiotics require refrigeration, while many others can be stored at room temperature.
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