Lactobacillus rhamnosus LGG®
Lactobacillus rhamnosus GG (LGG®) is a very well-known probiotic strain. Its properties have been explored in approximately 800 studies and 200 clinical trials. It is classified as a strain from the Lactobacillus rhamnosus species. It is very robust and has a high survival rate through gastric juices, with good adhesion to intestinal epithelial cells. Lactobacillus rhamnosus GG® strain also stimulates intestinal epithelial cell proliferation, and enhances secretion of protective mucins which protect the integrity of the gut epithelium, therefore making it ‘hardier’ against the effects of pathogens, antibiotics and negative dietary factors. Lactobacillus rhamnosus GG® is known mainly for its ability to enhance and support immune function, and for its positive effects on digestion (Mack D.R. et al., 2003), (Mack D.R., et al., 1999), (Lee, 2009).
Lactobacillus rhamnosus LGG – Safety and Survival
Lactobacillus rhamnosus LGG is a strain commonly found in food supplements, both as a stand-alone and combined ingredient.
There are studies, such as the one performed by DebMandal, M. et al (2015), which have demonstrated the strains’ ability to survive a broad pH range; pH 3-7, in vitro. Indicating a good survival potential through gastric challenges.
Safety and tolerability data from a 6 year cohort study was retrieved and analysed by Manzoni et al., 2011. The study had administered 3 billion CFU L. rhamnosus LGG to very low birth weight infants from the 4th day of life for a 4-6 week duration. On assessment, Manzoni et al., (2011), reported ‘no adverse effects or intolerances putatively attributable to LGG occurred’, concluding that Lactobacillus rhamnosus LGG is ‘microbiologically safe and clinically well tolerated’.
While this particular demographic is routinely advised to seek medical advice before supplementing, this study acts to demonstrate safety and tolerability, even in a vulnerable group for an extended period of time, which goes further to imply safety and tolerability in the general, healthy population for which food supplements are intended.
Smith, T. et al (2013). Reported an improved health related quality of life score by participants receiving a 2 strain supplement, including L. rhamnosus LGG for upper respiratory related symptoms, compared to placebo.
Lactobacillus rhamnosus GG® and Diarrhoea
A collection of different studies suggest that LGG® may help to alleviate diarrhoea symptoms caused a variety of factors, including antibiotic-associated diarrhoea, and travellers’ diarrhoea.
Antibiotic-associated diarrhoea can be a particular issue for those who are receiving aggressive antibiotic treatment for Helicobacter pylori infection. This pathogen is also notoriously difficult to eradicate, and so one triple-blind, placebo-controlled study assessed the efficacy of two different probiotics and one probiotic combination in preventing side effects associated with anti-Helicobacter pylori triple therapy, and also for their ability to improve the overall eradication rate of the pathogen. A total of 85 Helicobacter pylori positive, asymptomatic patients were randomly placed into four groups to receive either one of the probiotic supplements or placebo, both during treatment and for a seven days after triple therapy treatment had ended.
The subjects in Group 1 received a supplement containing Lactobacillus GG®; those in Group 2 received a supplement containing the probiotic yeast, Saccharomyces boulardii; those in Group 3 received a supplement containing a combination of Lactobacillus spp. and Bifidobacteria, and participants in Group 4 received a placebo supplement. All subjects filled in a symptom questionnaire every week for a period of four weeks. In all probiotic-supplemented groups, there was a significantly lower incidence of diarrhoea, and overall tolerance of the medication was significantly better than in the placebo group. There was no difference between probiotic groups and placebo in terms of theHelicobacter pylori eradication rate (Cremonini F, et al, 2002).
An earlier pilot study monitored the effects of probiotic therapy on 120 volunteers who had been diagnosed with H. pylori infection. The subjects were randomised to receive the standard triple therapy for one week, alongside a supplement containing either the probiotic LGG®, or a placebo. Both probiotic and placebo supplements were taken during the triple therapy and for a week afterwards. The common side effects of triple therapy - typically bloating, diarrhoea and taste disturbances -were significantly reduced in the group taking L. rhamnosus GG® compared to the placebo (Armuzzi A. et al., 2001b).
Lactobacillus rhamnosus GG® has also been tested for its ability to alleviate antibiotic-associated diarrhoea symptoms in children. In a randomised, double-blind, placebo-controlled trial, which used 200 children aged between 6 months and 10, all being treated with oral antibiotics, the subjects were either given a supplement containing LGG® or a placebo. The results were encouraging: twenty-five children in the placebo group developed diarrhoea symptoms compared to just seven in the LGG®-treated patients (Vanderhoof J.A. et al., 1999).
Travellers’ diarrhoea can be an extremely unpleasant hazard of foreign travel in under-developed countries, due to increased exposure to pathogens such as Escherichia coli and Salmonella. The potential of probiotics to offer protection against the incidence of travel-associated diarrhoea has been the subject of considerable scientific interest.
Further relevant studies: Armuzzi A. et al., (2001) Armuzzi A, et al (2001b), Arvola, T. et al., (1990), Cremonini F. et al., (2002), Fox M.J., (2015), Korpela K. et al., (2016), Manley K. et al., (2007), McFarland L.V., (2015), Oksanen P.J. et al., (1990), Vanderhoof et al., 1999).
Lactobacillus rhamnosus GG® and Diarrhoea in Children
Prolonged diarrhoea symptoms can be particularly serious in infants, and so some of the studies in this area of research have focused specifically on the alleviation of loose stools in children. Diarrhoea symptoms in children often occur in a hospital setting, compromising the recovery of patients who have been hospitalised for other reasons.
A polish trial was conducted on 81 hospitalised children aged between one month and three years, to see if prophylactic probiotics would help to prevent them from developing nosocomial diarrhoea (that is, diarrhoea originating in a hospital setting). The children were randomised to either take a dose of LGG® twice daily or a placebo. The results showed that administration of the probiotic significantly reduced the risk of diarrhoea in the infants, in particular, rotavirus gastroenteritis (Szajewska H., et al., 2001).
Two studies in India comprising of 235 and 559 children suffering with persistent diarrhoea in a hospital setting, and assessed the effects of differing strengths of probiotic supplements on their symptoms. The children were randomised to be given different strengths of Lactobacillus rhamnosus GG® or a placebo, for a minimum period of 7 days. It was found that all doses of LGG® (60 million, 10 billion, and 1 trillion) were equally effective at decreasing the duration and frequency of the diarrhoea in the children (Basu et al., 2009a, Basu et al., 2007b).
Further relevant studies: Ahmadi E. et al., (2015), Basu et al., (2007c), Canani et al., (2007), Guarino et al., (1997), Shornikova et al., (1997), Szajewska et al., (2007), Szajewska H., (2013).
Also relevant: see all strains which have been researched for diarrhoea (in all ages).
Lactobacillus rhamnosus GG® and Irritable Bowel Syndrome (IBS)
Irritable Bowel Syndrome (IBS) is a collective term used to describe a group of common chronic digestive symptoms, including bloating, cramps, diarrhoea and constipation. The exact cause of the condition is not known, but some people find that lifestyle factors, stress, and certain foods exacerbate symptoms. Pharmaceutical treatments have only limited success, and so the use of probiotics is being explored as a possible natural adjunct to conventional treatments (Pedersen N., 2014).
To test this potential, 123 patients who had been diagnosed with IBS were recruited to be part of an un-blinded trial. The patients were randomised into three groups: one group was told to take a supplement containing the probiotic strain LGG®, another group was instructed to follow a low FODMAP diet, and a control group was instructed to follow a standard Danish diet for six weeks. To monitor any changes in their symptoms, participants were required to complete IBS severity score system (IBS-SSS) and IBS quality of life (IBS-QOL) questionnaires each week. It was found that both the low FODMAP diet and probiotic supplement offered beneficial effects compared to a normal diet without probiotics for patients with IBS (Pedersen N., 2014).
Functional abdominal pain (FAP) is a common symptom of IBS and has no reliable cure; it can be severe and causes considerable distress, particularly in children. A double-blind, randomised, controlled trial studied 104 children who fulfilled the Rome II Criteria for IBS, or who suffered from functional abdominal pain or functional dyspepsia (FD). The patients were given either a supplement containing L. rhamnosus GG®, or a placebo supplement. By the end of the trial, the frequency of abdominal pain was significantly alleviated in the L. rhamnosus GG® group compared to the placebo group (Gawronska et al., 2007).
Lactobacillus rhamnosus GG® and Immunity
Although the mechanisms are not fully understood, it is believed that probiotic microorganisms may have modulating effects on the actions of pro-inflammatory and anti-inflammatory cytokines (Schultz M. et al., 2003). Lactobacillus rhamnosus GG® has been used in studies which have indicated that it has some notable ability to modulate the immune system.
In order to demonstrate the effect of Lactobacillus rhamnosus GG® on the cellular immune response to intestinal microorganisms in ten healthy volunteers, an open, non-blinded, non-controlled study was conducted. For the purposes of the study, the 10 adult participants were given a supplement containing 2 billion live cultures of the strain Lactobacillus rhamnosus GG®, every day for five weeks. Both stool and blood samples were taken prior to the study, and also after the last dose of the probiotic. To monitor the effects on immune function, pro- and anti-inflammatory cytokines (IL-10, IL-4, IL-6, IFN-gamma, TNF-alpha) were measured, as well as T-lymphocyte activation. After the probiotic treatment, the action of T-lymphocytes was increased in response to isolated and heat-inactivated intestinal microorganisms. Additionally, it was seen that there was decreased secretion of TNF-alpha, IL-6 and in part IFN-gamma cytokine secretion by PB cells, whereas the secretion of anti-inflammatory IL-10 and in part IL-4 cytokine secretion was increased at the end of the study (Schultz M. et al., 2003).
Further studies have been conducted to explore the effects of LGG® on genetic expression patterns in the small bowel mucosa. As part of the study process, 6 male adults with endoscopically proven oesophagitis were given Esom*****ole for a month, along with a supplement containing either Lactobacillus rhamnosus GG®, or a placebo. Biopsies of the duodenum were taken before and after this treatment. Microanalysis revealed regulation of particular genes: up-regulating 334 genes and down-regulating 92 genes, most of which are involved in immune response, inflammation, cell growth, cell differentiation, cell adhesion and signal. It was concluded therefore that this strain is associated with the complex genetic expression in the small bowel (Di Caro S. et al., 2005).
L. rhamnosus GG® has also been studied alongside vaccines, to see how the body’s immune system responds to a vaccine with probiotic intervention. The results of this can been seen in two different studies, where supplementation with LGG® appeared to be associated with an improved immune response to both influenza and polio vaccines. The positive effects were believed to be due to LGG® increasing levels of neutralising antibodies and antigen-specific IgA mucosal antibodies (de Vrese M. et al., 2005), (Davidson L.E. et al., 2011).
Further relevant studies: Hatakka et al., (2001), Hojsak et al., (2010a), Hojsak et al., (2010b), de Vrese M. et al., (2005).
Lactobacillus rhamnosus GG® and Allergies
An allergy is classed as an inappropriate immune response to a benign factor that, under normal circumstances, the body would not recognise as harmful. It is believed that certain beneficial bacteria may positively influence and balance this immune system dysregulation, and consequently this is an expanding area of probiotic research. Lactobacillus rhamnosus GG® is one of the strains which has been studied for its ability to help regulate immune system responses.
One related study attempted to demonstrate that Lactobacillus rhamnosus GG® may have a positive effect on the oral immune response. The research team recruited 38 patients, all with a known allergy to birch pollen, and divided them into two equal groups of 19, a treatment group and a control group. Participants in both groups began taking a supplement five and half months before the birch pollen season began; those in the treatment group received a supplement containing LGG®, and those in the control group were given a placebo. The results showed that, after 5 months of supplementation, increased allergen specific IgA levels in saliva were observed in the probiotic treatment group. The authors concluded that LGG® showed immune-stimulating effects in the oral mucosa, and that taking a probiotic may help to support those with allergy symptoms (Piirainen L, et al., 2008).
Allergies symptoms tend to run in families, a predisposition known as atopic sensitivity. Some studies have attempted to determine whether probiotic intervention during the perinatal period could reduce the risk of some of these diseases, but more research is needed to confirm this effect. However, after examining the data from four double-blind, randomised, placebo-controlled trials which took place between 1997 and 2012, a team of scientists concluded that ‘perinatal probiotic administration is safe and may have the long-term effect of decreasing allergy prevalence’.
The study authors examined data from a combined total of 303 mother-infant pairs (placebo group: n = 140; probiotic group: n = 163) included in the analysis. They noted that studies 1 and 4 used Lactobacillus rhamnosus GG® alone in the probiotic treatment group; study 2 used both Lactobacillus rhamnosus GG® and Bifidobacterium lactis BB-12 ® in the probiotic group, whereas study 3 used two kinds of probiotic combinations: Lactobacillus rhamnosus LPR with Bifidobacterium longum BL999, or Lactobacillus paracasei ST11 and Bifidobacterium longum BL999. Outcomes were measured in terms of asthma, allergic rhinitis, and food allergy symptoms.
The results found that the children who received supplements containing the combinations of other probiotics showed no notable improvements in their allergy symptoms, compared to their control (placebo) groups. However, in the 133 children who received LGG® either as a single strain or combined with other probiotics, a significantly decreased occurrence of allergic disease (59 of 133, 44.4%) was noted, compared to the children in the corresponding placebo groups (79 of 140, 56.4%) (Lundelin K. et al., 2017).
Further relevant studies: Cosenza L. et al., (2015), Fooland, (2014), Harb H. et al., (2013), Isolauri et al., (2000), Kalliomaki et al., (2003), Kalliomaki et al., (2007), Marschan et al., (2008), Pohjavuori et al., (2004), Rinne et al., (2005), Viljanen et al., (2005a), Viljanen et al., (2005b), Viljanen et al., (2005c).
Lactobacillus rhamnosus GG® and Ulcerative Colitis
Ulcerative colitis is one form of inflammatory bowel disease (IBD). Crohn's disease (CD) and ulcerative colitis (UC), are chronic disorders which are collectively referred to as ‘inflammatory bowel diseases’ (IBD). IBD is becoming increasingly common in Western Europe where it affects approximately 50 people in every 100,000. The exact causes of the conditions are unknown, though it’s believed that genetic factors leading to inappropriate function of the gastrointestinal immune response are key triggers in the development of IBD (Zocco M.A. et al., 2006). Probiotics are receiving considerable attention from scientists in order to fully explore their ability to positively influence immune responses in IBD, and most of the world's best, most well-researched, probiotics, as featured in this database, will have been used in studies focusing on this outcome.
To test this potential in the LGG® strain, 187 patients with ulcerative colitis were randomised to receive either a probiotic supplement containing LGG®, the drug mesalazine (an anti-inflammatory), or a combination of LGG® and mesalazine. The aim of the study was to prompt and evaluate a sustained remission for the patients. Overall, the results indicated that there was no difference in the relapse rate at either six or twelve months among the three groups. However, the treatment with Lactobacillus rhamnosus GG® was as effective as mesalazine alone, in prolonging a relapse-free time. The researchers concluded therefore that Lactobacillus rhamnosus GG® seems to be an effective and safe method for maintaining remission in patients with ulcerative colitis (Zocco MA. et al, 2006).
Also relevant: see all strains in the database which have been researched for IBD.
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Information on this strain was gathered by Joanna Scott-Lutyens BA (hons), DipION, Nutritional Therapist; and Kerry Beeson, BSc (Nut.Med) Nutritional Therapist.