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Probiotic research on metabolic syndrome, digestive health, and immune health.
Probiotic dietary supplement research is now exploring applications for metabolic syndrome, in addition to digestive health and immune health.
Dietary supplement research over the last several years has increasingly highlighted the potential of probiotics-various bacterial organisms which, when administered orally to humans, interact with the host in a way that influences the health and well-being of a number of body systems and processes. It’s clear that the overall balance of the gastrointestinal flora is a direct, major determinant in digestive health and disease. It is also clear that the bacterial inhabitants of the digestive tract have a major influence on local and systemic immune function. Several estimates suggest that upwards of 70% of the human immune system resides in the digestive tract, so it follows that there is ample opportunity for the microbial inhabitants of the intestines to interact and influence overall immune function.
Beyond digestive health and immune function, however, strong emerging research indicates that probiotic organisms can have a major influence in several other areas of interaction with the host. An exciting area of developing interest is the influence that certain probiotic organisms have on metabolic health. As metabolic syndrome is becoming an increasing public health burden, it is apparent that creative and effective measures are needed to combat the increasing prevalence of metabolic dysfunction, including insulin resistance, abdominal obesity, and liver health issues.
Preliminary studies in animals have highlighted the important potential benefits that specific organisms confer on several parameters related to metabolic health. Initial studies in humans are now confirming these effects, although additional research is needed to investigate the specific benefits probiotic organisms may provide in these areas.
While research on probiotics now spans several decades, this article aims to highlight some recent developments on the clinical front in the areas of digestive health, immune health, and the emerging area of metabolic health. Also highlighted are challenges that remain in fully harnessing the vast therapeutic promise that probiotic organisms hold for enhancing human health.
In the area of digestive health, research over the last several years has indicated benefits with probiotic supplementation, especially as it relates to common digestive symptoms, irritable bowel syndrome (IBS), and even inflammatory bowel conditions.
A recent study (Journal of Clinical Gastroenterology, July 2011) conducted by Dr. Tamar Ringel-Kulka’s group at the University of North Carolina assessed the effectiveness of a combination of two probiotic strains, Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07, in individuals with functional bowel disorders (including IBS) displaying a non-constipation subtype. In this eight-week study, participants were randomized to receive the probiotic combination (2×1011 CFU/day in two divided doses) or placebo. A major endpoint of the study revolved around the improvement in abdominal bloating. Significant improvements were noted in abdominal bloating and overall bloating severity at both four weeks and eight weeks compared with the placebo group. These changes were similar in the subgroup of participants with IBS.
A recent double-blind, placebo-controlled trial conducted in Italy by a group of researchers led by Dr. Simone Guglielmetti at UniversitÃ degli Studi di Milano in Milan and published in 2011 in the journal Alimentary Pharmacology and Therapeutics looked at the impact of daily supplementation with 1×109 CFU of the probiotic strain Bifidobacterium bifidum MIMBb75, compared to placebo, in 122 patients with IBS. After four weeks of supplementation, the probiotic improved IBS symptoms, including pain/discomfort, distension and bloating, and urgency. The global assessment of IBS symptoms was reduced significantly compared to placebo, while quality of life scores also improved significantly in the probiotic group. In addition, 47% of the group of patients on the probiotic reported adequate relief of symptoms at the end of the four weeks, whereas only 11% of those in the placebo group reported similar satisfaction.
The benefits of probiotics translate to a broad range of age groups, including children. As an example, a multicenter study published in the journal Pediatrics (December 2010) coordinated by Dr. Ruggiero Francavilla’s research group at the University of Bari in Italy included 141 children with functional abdominal pain. Children were given 3×109 CFU Lactobacillus GG (LGG), or placebo, twice daily for eight weeks and followed for an additional eight weeks. The primary outcome measure was overall pain, while an intestinal permeability test was also conducted at entry and at the end of the trial to assess gut barrier function. LGG supplementation resulted in a significant decrease in the frequency and severity of abdominal pain compared to the placebo group, with the differences compared to placebo still being significant at the end of the eight-week follow-up, indicating the persistence of beneficial effects of the probiotic strain even after supplementation had been discontinued. LGG also significantly improved intestinal permeability scores. No such improvement was seen with placebo. Thus, in children with functional abdominal pain, including as a result of IBS, LGG reduced abdominal pain and improved gut barrier function. The researchers noted that the improvements in gut barrier function may have led to the reductions in severity and frequency of abdominal pain.
Given that a large percentage of the human immune system resides in the digestive tract, and given the intimate interaction of microbes with various immune structures, it is clear that these interactions largely influence immune function. Several recent studies point to the ability of various probiotic organisms to enhance and improve the host response to viral infections, including the cold and flu virus.
A recent human study led by Anna Berggren of Probi Ltd., a Swedish research company specializing in probiotic development, and published in the European Journal of Nutrition (April 2011), investigated the effects of a combination of two specific probiotic strains on strengthening the immune response to the common cold. In the study, 272 subjects were supplemented with 1×109 CFU/day of a combination probiotic supplement containing Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2, or a placebo, for 12 weeks. The incidence of acquiring the common cold virus was significantly reduced from 67% in the placebo group to 55% in the probiotic group. Moreover, the number of days individuals suffered with cold symptoms was significantly reduced from a mean of 8.6 days in the placebo group to a mean of 6.2 days in the probiotic group. Total symptom scores were also significantly lower in the group supplemented with the probiotic combination than in the placebo group.
In another study, two trademarked probiotic strains, Bifidobacterium animalis ssp. lactis (BB-12) and Lactobacillus paracasei ssp. paracasei(L. casei 431), were studied separately in relation to placebo for their ability to augment the human immune response to the influenza vaccine. In a randomized, placebo-controlled study led by Giuliano Rizzardini from the Department of Infective Diseases at Luigi Sacco Hospital in Milan, Italy, and published in the British Journal of Nutrition (March 2012), 211 participants consumed either 1×109 CFU/day BB-12 (capsule) or L. casei 431 (dairy drink), or matching placebos, daily for six weeks. Two weeks into the regimen, individuals received a seasonal flu vaccine. Samples for analysis were taken at baseline and after six weeks to assess changes in antibodies, cytokines, and other immune parameters. In comparison to the placebo, both probiotic-supplemented groups showed increases from baseline in several vaccine-specific IgG immunoglobulins. In addition, significantly greater increases in vaccine-specific secretory IgA in salivary samples were seen in both probiotic groups as compared to placebo. Supplementation with either of the probiotics was deemed to be an effective way to augment systemic and mucosal immune responses associated with the seasonal flu vaccine, indicating the ability of both probiotic strains to modulate immune parameters.
Emerging research on probiotics suggests that certain organisms may play important roles in supporting optimal metabolic health parameters. As the incidence of metabolic syndrome in the general population approaches staggering numbers, it is essential to identify effective dietary and lifestyle measures that can benefit metabolic parameters. Research in animals, and now in humans, suggests that specific strains of probiotic organisms can impact markers of insulin resistance, visceral fat, and liver health, all of which are strongly linked to metabolic syndrome.
A Japanese research group affiliated with the Technology and Research Institute of Snow Brand Milk Products in Japan conducted a novel study to examine anti-obesity effects associated with supplementation of the probiotic strain Lactobacillus gasseri SBT2055. In the study published in the European Journal of Clinical Nutrition (June 2010), 87 individuals with BMI scores between 24.2 and 30.7 kg/m2 and increased abdominal visceral fat were randomly assigned to consume fermented milk containing the probiotic strain (5×1010 CFU/100 g of fermented milk), or fermented milk without the probiotic strain, daily for 12 weeks. In the group consuming the probiotic-fortified drink, abdominal visceral fat and subcutaneous fat areas decreased significantly by an average of 4.6% and 3.3%, respectively, from baseline levels. Significant decreases were also seen in body weight, waist circumference, and hip circumference in the probiotic group. In the control group (fermented milk only), none of these parameters showed significant differences. The results suggest that L. gasseri SBT2055 has a beneficial influence on several metabolic parameters.
Further trials have investigated the benefits of probiotic supplementation in patients with nonalcoholic fatty liver disease (NAFLD). A research group based at the University of Valladolid in Spain conducted a pilot clinical trial published in the European Review for Medical and Pharmacological Sciences (September 2011) in which 30 patients diagnosed with NAFLD were enrolled and randomized to supplementation with a daily probiotic mixture containing 5×108 CFU/day of Lactobacillus bulgaricus and Streptococcus thermophilus, or a placebo pill. The endpoints examined were changes in liver enzyme levels as indicators of liver function. In the probiotic group, significant decreases were seen in the liver enzymes ALT, AST, and GGT, following three months of supplementation. No such decreases were evident in the placebo group, indicating that supplementation with this probiotic mixture for three months improved liver function in patients with NAFLD.
Probiotic organisms clearly hold the promise of a broad therapeutic potential for a multitude of areas associated with human health. As further research is conducted, it is apparent that the number of areas impacted by probiotics is likely to grow; however, significant additional research is required to provide definition of the benefits conferred by specific species and selected strains.
First, it seems clear from the research that not all strains within a species provide identical benefits. While it is true that certain genera, Lactobacilli and Bifidobacterium being two of the most well-known, are present in large numbers in the digestive tract, they are not interchangeable from a therapeutic standpoint when administered orally. It is increasingly likely that strain selection will be an important factor in any potential benefits associated with a probiotic.
Secondly, not all species within a genus are hearty enough to survive gastric and bile acids when administered orally and thus will not be able to colonize the human digestive tract in an efficient enough manner to confer a benefit on the host.
Thirdly, issues remain with respect to optimal dosing. Some research suggests that high concentrations of bacteria are needed to confer health benefits; however, there are also studies showing that low doses of probiotics can also be effective. Clarity is needed with respect to ideal dosing and will require additional investigation.
Finally, there is the issue of combining probiotic strains and species and administering them simultaneously. While it is likely that certain combinations have additive benefits, it may also be true that other combinations are not beneficial. When it comes to supplementing with multiple strains, well-researched combinations are likely to provide consistent measurable benefits. Research also clearly shows that supplementation with single strains may be adequate and effective, and administration of multiple strains may not always be indicated.
Addressing these issues through well-conducted studies will serve to better define the therapeutic reach of these organisms and lead to the development of targeted strains that confer desired benefits.
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