Probiotic supplements have a positive impact on several health outcomes. However, the majority of published studies have focused on populations with specific health pathologies. Therefore, this study reviewed the current literature on the health effects of probiotic consumption in “healthy adults.” The findings from this review may help guide consumers, researchers, and manufacturers regarding probiotic supplementation. Relevant literature published between 1990 and August 2017 was reviewed. Studies were included if they were experimental trials, included healthy adults, used live bacteria, and had accessible full-text articles published in English. Included studies were classified according to common foci that emerged. Forty-five studies were included in this review. Five foci emerged: gut microbiota changes (n = 15); immune system response (n = 16); lipid profile and cardiovascular disease risk (n = 14); gastrointestinal discomfort (n = 11); and female reproductive health (n = 4). Results suggest that probiotic supplementation in healthy adults can lead to transient improvement in gut microbiota concentration of supplement-specific bacteria. Evidence also supports the role of probiotics in improving immune system responses, stool consistency, bowel movement, and vaginal lactobacilli concentration. There is insufficient evidence to support the role of probiotics to improve blood lipid profile. Probiotic consumption can improve in the immune, gastrointestinal, and female reproductive health systems in healthy adults. However, this review failed to support the ability of probiotics to cause persistent changes in gut microbiota, or improve lipid profile in healthy adults. The feasibility of probiotics consumption to provide benefits in healthy adults requires further investigation.
The use of fermented products can be traced back to ancient Egyptian and Middle-Eastern civilizations, when fermentation was a method of food preservation . However, it was not until the early 1900s that associations between human longevity and yoghurt consumption (containing lactobacilli strains of bacteria used for fermentation) were observed [2, 3]. It was also around this time when belief originated that fermented products could alter the microflora of the large intestine and reduce toxin production in the intestine [2, 3]. In the early 1900s Bifidobacterium was first isolated and was hypothesized to have anti-pathogenic effects . The next major advancement was in the 1960s, when the term “probiotic” was first coined for bacterial species deemed to be beneficial to the gastrointestinal (GI) tract. However, it was not until 2001 that the World Health Organization formally defined probiotics as “live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host” .
The ability of probiotics to impart health benefits has prompted increased scientific interest for several decades. Evidence from animal and human studies has demonstrated potentially favorable benefits of probiotics, including modulating the number and diversity of beneficial gut microbiota [5, 6]; reducing symptoms associated with various GI disorders [7, 8]; improving blood cholesterol levels and blood lipid profile [9, 10]; removal of mycotoxins ; reducing blood pressure and hypertension ; improving blood glucose tolerance and diabetes control [13, 14]; and enhancing mental state and cognitive function .
The translation of these health benefits in the public forum has led to increased demand for probiotic products/supplements over the last decade. This has prompted a rapid increase in the development of new probiotic-containing foods and supplements for the consumer market . While research has demonstrated positive effects of probiotic consumption on several health outcomes, the majority of the published literature is in populations with underlying pathologies. Evidence supporting the health-promoting effects of probiotics in healthy adults is limited and less consistent [17, 18]. Despite this, probiotic manufacturers promote the use of their product to a broader consumer market than those with specific health conditions. Whether probiotic supplementation conveys benefit in healthy individuals is questionable. Therefore, this study aimed to review the literature on the health effects of probiotic consumption in “healthy adults.” The results of this review may guide the decision-making of consumers, researchers, and manufacturers regarding probiotic supplementation.
Due to the number of outcomes included and the wide variety of studies varying in study design, experimental setting, and dependent measures (e.g., immune response to different viruses or a different population of older and younger adults), a systematic review was not performed. However, a systematic approach was employed to search and review the relevant literature. The online databases PubMed (MEDLINE), Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library (Central) were searched from 1990 through to August 2017. The reference lists of included studies were also manually searched for relevant studies. Following a PICOS (population, intervention, comparison, outcome, setting) approach, the online literature search used a combination of the following basic and MeSH (medical subject headings) terms: “healthy volunteers” or “healthy adults” as the population; “probiotics”, “lactobacillus”, or “bifidobacterium” as the intervention; “placebo” or “control” as the comparison; “controlled trials” or “non-controlled trials” as the study design. During the preparation and presentation of this review, the PRISMA guidelines were followed .
Study eligibility and selection
Studies were included if they (1) were experimental trials, (2) included adults, aged 18 years and older, (3) used live bacteria (probiotics), (4) included healthy adults, and (5) had accessible full-text publications in English. Healthy adults were defined as individuals with no reported status of the chronic or acute diseases, including cardiovascular disease (CVD), obesity (body mass index (BMI) ≥ 30 kg/m2), liver disease, diabetes, chronic GI problems, autoimmune disease, cancer, psychological disorder, etc. Adults who reported having symptoms consistent with the common cold, who were overweight (BMI 25–29.9 kg/m2) or smokers, were not excluded. Studies were excluded if probiotic treatment was mixed with other ingredients, or if pregnant women or both healthy and unhealthy adults were included as participants in one group.
The searched literature was initially screened by reviewing titles and abstracts. The full text of all relevant records was then reviewed. Two researchers were involved in the screening process and review of the literature. Eligible articles were only included when agreement was reached between the two researchers. In the case of any disagreement, a third reviewer was involved.
Data collection and synthesis
Eligible literature was classified based on the most prominent themes that emerged from the literature search. Studies with similar outcomes were grouped if more than three trials were classified in the relevant group [gut microbiota changes, immune system response, lipid profile and CVD risk, GI discomfort, and female reproductive health]. In each group, methodology characteristics and outcomes were extracted. A narrative synthesis was used to review the effect of probiotics consumption on outcomes in each classification. The Cochrane Handbook for Systematic Review of Interventions  was followed as a guideline to review literature.
Forty-five studies were included in the overall review. A summary of the review process and study selection criteria is presented in Fig. 1.
Gut microbiota colonization
The proposed health benefits of probiotics are often initially measured at the gut microbiota level . Changes in the concentration and composition of intestinal microorganisms would suggest that probiotics are effective, at least in terms of colonization . In all, 15 studies from the literature search were included in this classification group. Findings from these studies are summarized in Table 1. Of the 15 studies include, 14 suggested that probiotic supplementation is likely to increase the fecal count of specific bacterial strains administered in healthy adults. However, changes in the total count, diversity, and composition of gut microbiota were only reported in three studies [6, 21, 22]. It also appears that changes in the gut microbiota of healthy adults following probiotic supplementation are temporary and return to pre-treatment levels within 1–3 weeks once supplementation has ceased [23, 24].
No obvious conclusions regarding the effects of dose, duration or strain of probiotics on changes in gut microbiota can be made based on the studies included in this review (Table 1). In order to transition through the GI tract and colonize the gut, probiotics need to be viable (i.e., contain adequate live bacteria) and resistant (i.e., survive) to stomach acidity and bile salts [25, 26]. Some probiotic strains of the Bifidobacterium and Lactobacillus species such as B. animalis lactic, L. acidophilus johnsonii [27, 28], and L. casei Shirota  are reported as being resistant to low pH environments, thus appear to have good survival rates. In addition, L. acidophilus, B. longum, and B. infantis have demonstrated good resistance to bile salts [30, 31]. Encapsulation and microencapsulation manufacturing techniques have provided more efficient ways of delivering probiotics and preserving their viability . Although these methods may improve the survival of bacteria, they do not guarantee colonization of the probiotic bacteria in the intestine. The type of bacteria and the GI environment  also influence bacterial colonization. However, colonization may not necessarily be required for changes in the gut microbiota . The passage of probiotic bacteria (e.g., bifidobacteria) itself through the gut may be sufficient to reduce colonies of pathogenic bacteria by reducing their adhesion and competitive nature .
An ideal environment modulating the colonization of probiotics is one with adequate food to support the growth of healthy bacteria and reduce competition . The host’s diet is an important determinant of gut microbiota biodiversity. Fermentable carbohydrate supports the growth and colonization of selective bacteria in the gut. The term “prebiotics”  is used in reference to these fermentable fibers that resist gastric acidity and are able to stimulate the growth and activity of beneficial bacteria in the gut . Although commercially available (i.e., inulin, fructo-oligosaccharides, and galacto-oligosaccharides), these fibers are abundant in natural foods such as fruits and vegetables . Evidence suggests that prebiotic consumption can improve the fecal count of beneficial bacteria (especially bifidobacteria) [37, 38] and maintain gut health.
When gut microbiota dysbiosis exists (e.g., diarrhea), prebiotics alone may not be able to return gut microbiota to its equilibrium. Despite skepticism about the influence of probiotics on the gut microbiota of healthy adults, probiotics have proven beneficial effects when dysbiosis exists [7, 39]. Aging is also associated with a relative dysbiosis in gut microbiota. Reductions in bifidobacteria count, diversity, and an increase in pathogenic bacteria are observed in the elderly [40, 41]. Lahti et al.  reported that probiotic supplementation in healthy elderly adults could improve this age-related dysbiosis (Table 1). Overall, it seems that probiotic supplementation in healthy adults can lead to an increase in the colonization of specific probiotic strains. However, this increase may be transient and return to baseline after supplementation stops. Further studies need to focus on the sustainability of probiotic colonization in gut microbiota.
Immune system response
Probiotics have been proposed to improve intestinal defense mechanisms against pathogenic microorganisms, enhance the immune system, and reduce the likelihood of respiratory infections [42, 43]. Sixteen studies from the literature search were included in this classification group, with findings summarized in Table 2. Eight studies reported the effect of probiotic consumption on common respiratory infections such as cold and flu. All of the three studies reporting on the effect on the common cold support a beneficial effect of probiotic supplementation at increasing immunity against the common cold in healthy adults (albeit in a limited number of studies; Table 2). Reductions in the incidence [44, 45], duration [44, 46], and symptoms [44, 46] associated with common cold are commonly observed in healthy adults when a probiotic intervention is administered.
In contrast, the effect of probiotic supplementation on immune responses against influenza infection in healthy adults is less consistent [43, 47, 48]. In vitro exposure of T cells collected from 10 individuals (supplied with probiotics for 30 days) to the influenza A virus showed a significant increase in TNF-α . This suggests enhancement of T-cell responses to a respiratory tract infection. These findings are supported in a larger study (n = 465 participants supplemented with probiotics for 150 days), which indicated a significantly reduced risk of respiratory illness . However, these findings are in contrast with the results of several other studies indicating that probiotic supplementation had no influence on the incidence [47, 48, 50] or severity [47, 48] of the flu.
The effect of probiotics on immune function of healthy adults are summarized in Table 2. Ten studies reported improvement in the immune function by activating T lymphocytes, including cytotoxic plus and T helper cells (CD8+ and CD4+) after probiotic consumption [46, 51, 52], increase natural killer (NK) cell activity [45, 51, 53, 54], reduce the pro-inflammatory cytokines interleukin (IL)-12, IL-6, and IL-4 [51, 53, 55], and increase anti-inflammatory cytokines IL-10 [53, 56]. However, there is no consistent and clear relationship between the effects observed and the dose, duration, and type of probiotic strains administered. Overall, it appears that probiotic supplementation in healthy adults can improve immune function and the immune response to common cold infections. However, the immune response to influenza infection and the effective duration, dose, and type of probiotics supplementation require further investigation.
Lipid profile and CVD risk
Elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), low levels of high-density lipoprotein cholesterol (HDL-C), increase in BMI, blood glucose, and pro-inflammatory markers are major risk factors of CVD . The potential of probiotics to support a reduction in inflammation markers in healthy adults has been discussed in the previous section. The effect of probiotic consumption on changes to blood lipid profile has been investigated in several systematic reviews and meta-analyses [9, 58,59,60]. Collectively, findings from these reviews and meta-analyses suggest an improvement in blood lipid profile, especially in total cholesterol (TC) and LDL-C levels. However, these studies included both healthy and unhealthy adults (including conditions such as hypercholesterolemia, CVD, diabetes, and obesity). Thus, conclusions regarding the influence of probiotics on the blood lipid profile of healthy adults cannot be reliably determined from this work.
A summary of results from the present review of literature for the effect of probiotic consumption on blood lipid profile of healthy adults is presented in Table 3. Of the 14 studies (15 trials, 1 study with 2 separate arms ), 7 reported no significant changes in the concentration of various blood lipid profile markers following probiotic consumption [18, 55, 61,62,63,64]. Three studies reported a significant reduction in TC [61, 65,66,67]. Reductions in TG [67,68,69,70], LDL-C [61, 65], and an increase in HDL-C [66, 67] were also reported. Furthermore, in 1 study, 6 weeks of probiotics treatment in healthy adults who were heavy smokers  demonstrated improvements in markers of oxidative stress (F2-isoprostanes) and the pro-inflammatory marker IL-6, supporting the cardio-protective effect of probiotics. Despite this, to date only a small number of individual studies have demonstrated benefits of probiotics and the collective evidence is not inclusive for the beneficial effect of probiotics consumption on blood lipid profile of healthy adults.
Changes in BMI were reported in six studies (Table 3). Of these, four reported no significant changes [18, 55, 66, 70] and one reported a significant increase in BMI after probiotic supplementation . One of the studies assessed the BMI increase after 4 weeks of high-fat diet and reported a lower increase in BMI in the probiotic group compared to placebo . Due to a low number of studies included and inconsistent results, a conclusion cannot be reached for the effect of probiotics on BMI of healthy adults. Seven studies also reported changes in fasting blood glucose (FBG) and insulin levels. Of these, four reported no significant changes in FBG or insulin levels [55, 64, 70, 71], two reported a reduction in FBG and insulin level [62, 67], and one reported an increase in FBG after probiotic supplementation in healthy adults . Similar to BMI, the evidence is inconclusive for the beneficial effect of probiotics on FBG and insulin level in healthy adults.
Although underlying mechanisms of the effect of probiotics on lipid profile are not completely understood, the cholesterol binding and assimilation ability of probiotics and their ability to deconjugate bile salt (to reduce its solubility and absorbability) are proposed as the potential mechanisms of action . Bacteria in the gut also have the ability to produce short-chain fatty acids (SCFAs; such as acetate, butyrate, and propionate) through fermentation of dietary fibers . SCFAs are shown to lower hepatic cholesterol synthesis and regulate cholesterol metabolism . Both lactobacilli and bifidobacteria are able to produce SCFAs. Recently proposed next generation of probiotics such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also shown to have a high SCFA-producing ability from dietary fibers [74, 75].
Although constipation is often considered as a symptom of a health condition, irregularities in bowel movement, evacuation disorder, abdominal discomfort, and bloating may occur in response to aging and changes in dietary, lifestyle, and psychological factors in otherwise healthy individuals [76, 77]. These changes also influence the bacterial flora of the intestine. A diet high in fat, for example, is known to cause dysbiosis in gut microbiota . Aging has also been associated with a decrease in the number and diversity of bifidobacteria . Benefits of probiotic supplementation in the treatment and management of many types of diarrhea and constipation have been reported in unhealthy populations [7, 8]. Table 4 summarizes the evidence of the effect of probiotics consumption on GI health of healthy adults. Of the four studies included (six trials, two studies had two arms [61, 76]), an improvement in the bowel movement, defection frequency, and stool consistency was reported in five studies [61, 76, 77]. One study did not observe improvements in the colonic transit time or bowel movement . However, this study had the shortest duration of supplementation among the identified trials. Overall, it appears that probiotic supplementation may be effective at improving stool consistency, bowel movement, and reducing irritation caused by abdominal bloating. The relevant mechanisms of probiotics in this action remain unclear. However, fermentation of non-digestible carbohydrates and production of SCFA and carbon dioxide, removal of other intestinal gases , and the anti-inflammatory effect of probiotics have been suggested  as potential mechanisms.
Female reproductive system health
From birth until after puberty, lactobacilli are the predominant microorganisms populating the vaginal microbial environment . However, after puberty the microbial environment changes due to menstruation, hormonal changes, intercourse, infections, and hygiene . This often results in a vaginal environment that is not predominant in lactobacilli bacteria for the majority of women , increasing susceptibility to urogenital infections such as urinary tract infection and bacterial vaginosis . The effect of probiotic supplementation on maintaining female reproductive health is summarized in Table 5. Four studies (five trials, one study had two arms ) have examined the effects of oral supplementation or vaginal suppositories with lactobacilli as a means of improving the vaginal environment. Among these, four trials have suggested there was a significant increase in the level of vaginal lactobacilli [81, 84,85,86]. Supplementation with L. acidophilus, L. rhamnosus, or L. fermentum increased vaginal lactobacilli levels in healthy women [81, 84,85,86]. The increase in vaginal lactobacilli population seems to prevent and reduce the incidence of vaginal infections in otherwise healthy adult women .
Effect of probiotics on psychological health
Although the focus of this review thus far has been on physiological health outcomes, it is important to acknowledge that probiotics consumption may also influence psychological health—an essential domain of overall well-being. Conceptualization of the brain-gut axis has introduced a link between psychological health and gut microflora [87, 88]. Psychological distress can reduce the number and diversity of intestinal microorganisms by changing intestinal transit time, acidity, mucus secretion, stress hormones, and immune response . Conversely, the gut microbiota can influence a hosts’ nervous system (gut-brain axis) by producing signaling molecules (e.g., polypeptides) and modulating neuronal signaling mechanisms . A recent meta-analysis of five randomized controlled trials examining the effect of probiotics supplementation on depression score suggests that probiotics supplementation can induce a significant reduction in depression scale score . Although the reduction observed in the subgroup of individuals with major depressive symptoms (−0.73, 95% confidence interval (CI): −1.37 to −0.09, ρ = 0.03) was greater than their healthy counterparts (−0.25, 95% CI: −0.47 to −0.03, ρ = 0.03), the meta-analysis suggests probiotic consumption can reduce depression symptoms in healthy adults . Similarly, a recent systematic review and meta-analysis of seven randomized controlled trials indicate a significant improvement in subclinical symptoms (including reduced stress, depression, and anxiety; 0.34; 95% CI: 0.07 to 0.61, ρ = 0.01) can be achieved in healthy adults following probiotic supplementation . Both studies reported including trials with good methodology quality and low risk of bias. Collectively, evidence from these studies suggests that probiotic supplementation may improve psychological symptoms in healthy adults.
Demand for probiotic food and supplements has increased over the past few decades. Globally, the probiotic market is expected to have up to an 8% compound annual growth rate increase from 2014 to 2020 . This prompts continued interest in research regarding the health benefits of probiotics. Although consumption of probiotics has beneficial effects on several health outcomes, the majority of findings are related to populations with specific health conditions or disease. This raises an important question as to whether the health benefits provided by probiotics are limited to individuals with underlying pathologies. Thus, in the current review, we explored the effects of probiotics consumption in otherwise healthy adults. Overall, results from this review suggest that probiotics supplementation in healthy adults generate an improvement in gut microbiota. However, despite gut microbiota changes occurring with probiotics, these changes appear to be limited to a transient increase in the bacterial count of the specific strain administered. This implies that supplementation with probiotics may need to be an ongoing process in order to maintain gut microbiota changes in healthy adults. Gut microbiota is sensitive to multiple factors, such as lifestyle, aging, and disease. Even in apparently healthy individuals, changes in diet quality and alcohol intake can significantly affect gut symbiosis. A diet poor in fruit and vegetable intake (as a good source of prebiotics) may not provide the food required for probiotic survival and maintenance. This may explain the constant need for probiotic food and supplements to maintain gut symbiosis and health. Furthermore, in older adults with age-related dysbiosis, probiotic supplementation appears to improve and reduce dysbiosis.
The transient effect of probiotics on gut microbiota may also be explained by the viability of probiotic microorganisms. Evidence suggests that viability of probiotics could differ from the number of viable cells declared on the product label . Although drying processes during probiotic production may have a negative impact on viability, different drying methods (air-drying, freeze-drying, and spray-drying) have diverse effects on probiotic strains in terms of both viability and functionality . Although viability is acknowledged as a prerequisite for the health benefits of probiotics, few interventions have reported the viability of probiotics during the period of supplementation. Evidence suggests that non-viable probiotic strains may also confer some positive health outcomes  however, this requires further investigation.
The current review also suggests that probiotic consumption in healthy adults may improve immune function, particularly in response to common upper respiratory infections; reducing their incidence and/or symptom severity. This is particularly important since improved immune function via probiotics may reduce the antibiotic needs in infections, thus reduce the risk of antibiotic resistance —one of the greatest global threat of present decade . Probiotics may enhance the immune response by activating T lymphocyte cells, increasing NK cell activity and anti-inflammatory cytokines (e.g., IL-10), and reducing pro-inflammatory cytokines (e.g., IL-12 and IL14). These findings are in agreement with a recent meta-analysis (including both healthy and unhealthy populations) indicating that probiotic consumption may have a protective effect against the common cold . As gut microbiota is typically considered the first line of defense against pathogenic microorganisms in the intestine, maintaining symbiosis through regular consumption of probiotics foods and/or supplements is essential. This is particularly important in older adults, where age-related decreases in immune function  may increase vulnerability to a variety of infections.
The present review did not find sufficient evidence to support a blood lipid profile lowering effect of probiotics in healthy adults. These findings are in contrast with several systematic reviews and meta-analyses suggesting probiotic consumption facilitates improvements in blood lipids [9, 58,59,60]. This disagreement is likely due to the inclusion of both healthy and unhealthy (participants with a high baseline level of blood lipids) populations, hence a greater opportunity for improvements in lipid profiles was afforded in these previous reviews. Similarly, BMI, FBG, and insulin level of healthy adults were not significantly affected by probiotic consumption in the present review. These findings, however, are in contrast to previous systematic review and meta-analysis of the effect of probiotics on BMI  and FBG . This can be explained by the inclusion of participants with underlying pathologies (obese or diabetic). For example, Nikbakht et al.  included trials with high and normal FBG participants with an overall significant effect of probiotics consumption on FBG reduction. However, their subgroup analysis results showed no significant changes in participants with normal FBG level. This can explain the findings of the current review reporting no significant effect of probiotics on FBG of healthy adults.
The current review also found some evidence for the effect of probiotics as a means of relieving abdominal discomfort and improving bowel movement irregularities in healthy adults. Although probiotics have been reported as beneficial for these conditions , definitive conclusions cannot be made and further research is required to clarify these findings in healthy adult populations. Probiotic consumption also appears to offer some benefits in maintaining female reproductive health by improving the lactobacilli count of the vaginal environment to prevent urogenital infections. Again however, the low number of eligible studies included in this review suggest that further investigation is required to support any dietary guidance provided for these conditions.
Although the effect of probiotics supplementation on psychological symptoms of healthy adults was not reviewed in-depth in this paper—as this has already been done elsewhere—results of recent meta-analyses suggest improvements in depression, stress, and anxiety following probiotic supplementation [89, 90]. However, in most studies included in these meta-analyses, changes in gut flora were not reported. Furthermore, psychological symptoms are typically measured using subjective self-reported scales and questionnaires, with different scales often administered across studies. Thus, it is important to consider these limitations when translating the findings. Nevertheless, probiotic supplementation may confer psychological benefits in healthy individuals and further exploration of these effects is warranted.
To our knowledge, the present review is first to assess the evidence for a range of health-related outcomes of probiotic consumption in healthy adults. However, the present study does have some limitations. First, it was not possible to employ a complete systematic review approach due to the differences in study design, participant characteristics, and dependent measures included in this review. Therefore, it limited the potential of the review to assess the methodological quality and bias risk of included studies. However, of the 45 studies included in this review, the majority were randomized (n = 38), included blinding (n = 32) and had similar control or placebo groups (n = 38). Second, the low number of studies included in the review of GI health and female reproductive health outcomes limits the conclusions that can be drawn from these research areas. Also, probiotic characteristics are strain-specific and due to variations in the probiotic strains used in the included studies, a conclusion cannot be made on the effective strains.
With ongoing increases in the manufacturing and marketing of probiotics to the general public there is a need for the benefits of probiotics to be better understood. Although this review suggests that healthy adults (and in particular, older adults) may achieve some health benefits from the consistent use of probiotics, probiotic supplementation may have a similar fate to multivitamins. That is, they may be effective in specific cases or conditions. More research on the probiotic use is necessary to develop a stronger body of evidence for their efficacy across both healthy and unhealthy population groups. Additionally, interventions with follow-up periods are required to assess the sustainability of probiotic use and their effect in healthy adults. Until further research is conducted, the benefits and feasibility of probiotic consumption in healthy adults remain uncertain and it would be prudent to advise consumers that supplementation with probiotics may be more effective in specific population groups and those with underlying pathologies.
About this article
Survival of L. casei DG® (Lactobacillus paracasei CNCMI1572) in the gastrointestinal tract of a healthy paediatric population
European Journal of Nutrition (2018)