What is Lactobacillus rhamnosus

Lactobacillus rhamnosus GG (named after the first initials of the last names of two Tufts University researchers, Barry Goldin and Sherwood Gorbach) was the first strain lactic acid producing bacteria belonging to the genus Lactobacillus to be patented in 1989 thanks to its ability to survive and to proliferate at gastric acid pH and in medium containing bile, and to adhere to gut cells ¹. Lactobacillus rhamnosus GG (ATCC 53103) was originally isolated from fecal samples of a healthy human adult ². Lactobacillus rhamnosus is a gram positive, anaerobic bacterium that exhibits the capacity to transport and metabolize carbohydrates and thereby helps in maintaining the epithelial-layer gut integrity ³. Recently, a study demonstrated that Lactobacillus rhamnosus GG-administration alleviates gut inflammation and improved barrier function of intestine ⁴. Lactobacillus rhamnosus GG was identified as a potential probiotic strain because of its resistance to acid and bile, good growth characteristics and adhesion capacity to the intestinal epithelial layer ⁵. Probiotics are organisms (bacteria and yeasts) that are taken to improve health. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” ⁶. According to the Dietary Supplement Health and Education Act (DSHEA) of 1994, nutritional supplements, including probiotics, are considered food rather than drugs ⁷. They are not regulated for clinical application, which results in so-called health claims rather than disease-based claims. The DSHEA requires that dietary supplements meet current good manufacturing practices, but unfortunately, there are substandard products that meet this threshold. Ever since, Lactobacillus rhamnosus GG has been one of the most widely studied probiotic strains, used in a variety of commercially available probiotic products. The beneficial effects of Lactobacillus rhamnosus GG strain have been studied extensively in clinical trials and human intervention studies ². Furthermore Lactobacillus rhamnosus GG is able to produces both a biofilm that can mechanically protect the mucosa, and different soluble factors beneficial to the gut by enhancing intestinal crypt survival, diminishing apoptosis of the intestinal epithelium, and preserving cytoskeletal integrity.

Lactobacillus rhamnosus probiotic

The microbiome is the collection of all microbes, such as bacteria, fungi, viruses, and their genes, that naturally live on our bodies and inside us. Although microbes require a microscope to see them, they contribute to human health and wellness in many ways. They protect us against pathogens, help our immune system develop, and enable us to digest food to produce energy. Some microbes alter environmental chemicals in ways that make them more toxic, while others act as a buffer and make environmental chemicals less toxic. The intestinal microbiome is composed of microbes that reside in the gut and may be altered by diet, lifestyle, exposure to toxins, and antibiotic use ⁸. There is a relationship between disease, health, the immune system, and changes in the microbiota ⁸. Probiotics have an important role in the maintenance of immunologic equilibrium in the gastrointestinal tract through direct interaction with immune cells ⁹. The microbiome diversity is likely important in health maintenance, and it is likely that broad-spectrum probiotics may increase the effectiveness of treatment. The mechanisms of action of probiotics are complex and likely differ by species ¹⁰. Government regulation of probiotics in the United States is complex. Depending on a probiotic product’s intended use, the U.S. Food and Drug Administration (FDA) might regulate it as a dietary supplement, a food ingredient, or a drug. Dietary supplements are regulated by the U.S. Food and Drug Administration’s Center for Food Safety and Applied Nutrition ¹¹. If the probiotics are considered to be drugs for therapeutic purposes, then the product is regulated by the U.S. Food and Drug Administration using Current Good Manufacturing Practices and Investigational New Drug approval processes ¹².  Many probiotics are sold as dietary supplements, which don’t require FDA approval before they are marketed. Dietary supplement labels may make claims about how the product affects the structure or function of the body without FDA approval, but they aren’t allowed to make health claims, such as saying the supplement lowers your risk of getting a disease, without the FDA’s consent. If a probiotic is going to be marketed as a drug for treatment of a disease or disorder, it has to meet stricter requirements. It must be proven safe and effective for its intended use through clinical trials and be approved by the FDA before it can be sold.

Probiotic bacteria are proposed to benefit human health mainly by three general mechanisms of action ¹³. Firstly, certain probiotics can clearly exclude or inhibit pathogens, either through direct action or through influence on the commensal microbiota ¹⁴. A second mechanism is the capacity of certain probiotic strains to enhance the epithelial barrier function by modulating signaling pathways, such as nuclear factor-κB (NF-kB), Akt and mitogen- activated protein kinase (MAPK)-dependent pathways, which lead to for example the induction of mucus ¹⁵ or increased tight junction functioning ¹⁶. Thirdly, most probiotic strains can also modulate host immune responses, exerting strain-specific local and systemic effects ¹⁷. Many of the interactions between probiotic bacteria and intestinal epithelial and immune cells are thought to be mediated by molecular structures, known as microbe- associated molecular patterns, which can be recognized through specific pattern recognition receptors such as Toll-like receptors ¹⁸. Even though many experimental in vitro data and experiments in animal models validate these mechanisms for probiotic strains in general and for Lactobacillus rhamnosus GG in specific, most published in vivo data in humans pay less attention to mechanisms of action ².

Lactobacillus rhamnosus benefits

Lactobacillus rhamnosus GG is one of the most widely used probiotic strains. Various health effects are well documented including the prevention and treatment of gastrointestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms. However, not all intervention studies could show a clinical benefit and even for the same conditions.

Lactobacillus rhamnosus GG has been shown to colonize the gut of newborns significantly better than adults ¹⁹. Interestingly, prenatal supplementation with Lactobacillus rhamnosus GG (1.8×10¹⁰ colony forming units [CFUs] in capsules, daily from 36th week of gestation) has been reported to change the composition of the neonates microbiota, promoting a beneficial profile dominated by bifidobacteria ²⁰, although the overall microbial diversity did not seem to have changed ²¹. Others showed that postnatal application of Lactobacillus rhamnosus GG (10⁹ CFU daily, lyophilized powder mixed with breast milk) appears to affect neonatal intestinal colonization patterns causing a higher species diversity compared to placebo ²², although the analysis was not done at detailed level. How exactly Lactobacillus rhamnosus GG could promote the colonization of bifidobacteria in vivo remains to be further explored.

Given its excellent intestinal mucus adherence capacities, Lactobacillus rhamnosus GG has also been often selected as candidate probiotic for the prevention and treatment of gastrointestinal infections and diarrhea, although the efficacy is not uniformly proven. Three subsequent meta-analysis studies have discussed the use of Lactobacillus rhamnosus GG for the treatment of acute diarrhea in children ²³, ²⁴, ²⁵. Overall, the current data suggest that Lactobacillus rhamnosus GG can reduce the duration of diarrhea with 1.05 days, particularly in children from geographical Europe, treated with a high dose of Lactobacillus rhamnosus GG (≥10¹⁰ CFU/day). Lactobacillus rhamnosus GG (10⁹ CFU daily in fermented milk product) was also shown to reduce the risk of acquiring nosocomial gastrointestinal infections when administered daily in hospitalized children ²⁶. Undernourished Peruvian children showed a lower incidence of diarrhea when treated with Lactobacillus rhamnosus GG (>10¹⁰ CFU daily, lyophilized powder mixed with liquid cherry gelatin). Effects were the largest in non-breastfed children ²⁷. However, long-term consumption of milk containing Lactobacillus rhamnosus GG (10⁸ CFU daily) in children attending day care centers in Finland could not show an effect on the incidence of gastro-intestinal symptoms ²⁸. It is important to note that the unsuccessful trial tested a 100-fold lower daily concentration, although other factors such as probiotic formulation and study subject heterogeneity could of course also play a role ². A recent meta-analysis concluded that Lactobacillus rhamnosus GG treatment can also reduce pain frequency and intensity in children with abdominal pain-related disorders, particularly among irritable bowel syndrome (IBS) patients ²⁹. However, it is important to mention that the clinical effects were significant but moderate ²⁹, which is not unexpected if you consider the large subject heterogeneity in IBS patients.

In other conditions, Lactobacillus rhamnosus GG effects were better stratified. For instance, oral supplementation with Lactobacillus rhamnosus GG (6 × 10⁹ CFU with human milk) has been shown to prevent enteric colonization by Candida species in preterm neonates in a randomized study ³⁰, although the underlying mechanisms need to be explored. Two pilot studies also showed promising results for Lactobacillus rhamnosus GG treatment (respectively 10¹⁰ CFU in skim milk and 1.2 × 10⁹ CFU in lyophilized powder daily) of recurrent Clostridium difficile induced colitis in children ³¹, ³², but this should be repeated in larger trials. Furthermore, application of a commercial yoghurt with Lactobacillus rhamnosus GG to renal patients during 8 weeks has been shown to succeed in clearing vancomycin-resistant enterococci in all patients in an double-blind, randomized, placebo-controlled trial ³³. A larger single-blind, randomized, placebo-controlled trial focused on children (3 × 10⁹ CFU daily, dissolved in water or milk) and could show a significant difference between the treated and the control groups only after three weeks ³⁴. The mechanism of clearing of this vancomycin-resistant enterococci remains to be explored, but the SpaCBA pili of Lactobacillus rhamnosus GG share some sequence identity (30-40%) with the pili of Enterococcus faecalis and Enterococcus faecium ³⁵. Clearly, experiments with non-GMO pili deficient variants of Lactobacillus rhamnosus GG would be highly interesting to study their role in the gastro-intestinal and pathogen exclusion effects of Lactobacillus rhamnosus GG.

Although many intervention studies with Lactobacillus rhamnosus GG are targeting the gastrointestinal, it is also interesting to investigate extra-intestinal effects of Lactobacillus rhamnosus GG. For instance, Lactobacillus rhamnosus GG has been shown to reduce oral counts of Streptococcus mutans, a bacterium correlated with caries formation, respectively in yogurt, milk and lozenges ³⁶. Especially long-term consumption of Lactobacillus rhamnosus GG containing milk (5-10 × 10⁵ CFU) appears to be able to reduce tooth decay development in children ³⁷. Of note, there was no effect of short-term consumption of Lactobacillus rhamnosus GG (4×10⁸ CFU daily) on the acidogenicity of plaque nor on caries formation in adults, although it should be noted that Lactobacillus rhamnosus GG was administered in a tablet, which might not be the best formulation ³⁸. Importantly, Lactobacillus rhamnosus GG appears not to ferment sucrose to a significant level ³⁹, indicating that it is itself not cariogenic, a property which is sometimes attributed to lactobacilli due to lactic acid production.

Others have investigated the effect of Lactobacillus rhamnosus GG consumption on respiratory health. For instance, Hojsak and colleagues ²⁶ showed that fermented milk containing Lactobacillus rhamnosus GG was efficient in reducing the risk on respiratory tract infections (RTIs) that lasted longer than three days in hospitalized children. Also, preterm infants treated daily with 10⁹ CFU Lactobacillus rhamnosus GG in capsules starting within one week after birth, appear to have significantly lower incidence of respiratory tract infections and rhinovirus-induced episodes in the first 2 months ⁴⁰. Furthermore, capsulated Lactobacillus rhamnosus GG (10⁹ CFU) was shown to protect hospitalized patients against ventilator-associated pneumonia, mainly when caused by Gram-negative pathogens like Pseudomonas aeruginosa ⁴¹. Moreover, in cystic fibrosis patients colonized with Pseudomonas aeruginosa, long-term Lactobacillus rhamnosus GG treatment (6×10⁹ CFU daily, in oral rehydration solution) significantly decreased the incidence of pulmonary exacerbations and increased body weight ⁴². Unfortunately, this study did not evaluate Pseudomonas aeruginosa colonization status after Lactobacillus rhamnosus GG treatment. Clearly this area requires further research, because probably a combination of Lactobacillus rhamnosus GG’s antipathogenic and immune modulating capacities determines its potential in respiratory tract infections ².

Acute infectious diarrhea

Probiotics are effective for acute infectious diarrhea caused by bacteria, but there are inconsistent results for the effectiveness of probiotics for diarrhea caused by viruses. A Cochrane review of 63 randomized controlled trials and quasi-randomized controlled trials included 8,014 infants, children, and adults with acute infectious diarrhea. The researchers found that probiotics significantly reduced the mean duration of diarrhea (25 fewer hours); decreased the risk of diarrhea lasting four or more days by 59%; and led to approximately one fewer stool on day 2 ⁴³. For patients with acute infectious diarrhea, probiotics should be started at the onset of symptoms and although there is no evidence to support length of treatment, researchers suggest continuing for one to two weeks following the resolution of symptoms. A meta-analysis of 12 randomized controlled trials with 5,171 participants found a 15% relative decrease in the risk of traveler’s diarrhea with probiotic use ⁴⁴. For prevention of traveler’s diarrhea, probiotics should be started two days before travel and continued throughout the trip.

A meta-analysis of 17 randomized controlled trials in 2,102 children comparing Saccharomyces boulardii probiotic vs. control for the treatment of acute diarrhea showed a significant reduction in the duration of diarrhea with probiotic use (20 fewer hours) ⁴⁵. Another meta-analysis of eight randomized controlled trials involving 1,229 children found that Lactobacillus reuteri administration reduced the duration of diarrhea (25 fewer hours) and increased the cure rate on days 1 and 2 ⁴⁶. However, an randomized controlled trial of 646 children with acute watery diarrhea caused predominantly by rotavirus found no significant difference between the group that received Lactobacillus rhamnosus GG probiotics and the control group in the daily frequency of stools, duration of diarrhea, vomiting, or length of hospital stay ⁴⁷. A meta-analysis of two randomized controlled trials in 201 children with diarrhea from rotavirus found a significant reduction in diarrhea in those treated with Lactobacillus rhamnosus GG vs. placebo (two fewer days) ⁴⁸.

Antibiotic-associated diarrhea

Probiotics are effective for the prevention and treatment of antibiotic-associated diarrhea in children and adults, and the prevention of Clostridium difficile–associated diarrhea in children and adults; however, there are conflicting results for Clostridium difficile infection. Patients should start probiotics on the first day of antibiotic treatment and continue for one to two weeks following completion of antibiotic therapy. To simplify the treatment regimen, patients may take probiotics at the same time as antibiotics. A Cochrane review of probiotics for the prevention of antibiotic-associated diarrhea in children (23 studies with 3,938 participants) reported that children treated with probiotics vs. control were less likely to have antibiotic-associated diarrhea (absolute risk reduction = 11%; number needed to treat = 10) ⁴⁹. The Cochrane review review found that Lactobacillus rhamnosus GG or Saccharomyces boulardii at 5 to 40 billion colony-forming units (CFUs) per day was effective, with rare adverse events. In an randomized controlled trial of 333 hospitalized children receiving antibiotics, diarrhea prevalence was lower in children receiving Saccharomyces boulardii probiotics compared with oral rehydration (absolute risk reduction = 21%; number needed to treat = 5). There was also a reduced risk of antibiotic-associated diarrhea, including Clostridium difficile–associated diarrhea and culture-negative diarrhea (absolute risk reduction = 15%; number needed to treat = 7), as well as significantly lower stool frequency, higher recovery rate, and shorter mean duration of diarrhea (2.3 vs. 9.0 days) ⁵⁰.

A meta-analysis of 63 randomized controlled trials with 11,811 children and adults that compared probiotics with placebo or no treatment reported a significant reduction in the risk of antibiotic-associated diarrhea (number needed to treat = 13) ⁵¹. A meta-analysis of adult inpatients showed a reduction in antibiotic-associated diarrhea (15 randomized controlled trials; 2,296 patients; number needed to treat = 11) and a reduction in Clostridium difficile infection (nine randomized controlled trials; 1,099 patients; number needed to treat = 14) among patients randomly assigned to probiotics vs. placebo ⁵². A Cochrane review of 23 randomized controlled trials reported that probiotics significantly reduced the risk of Clostridium difficile–associated diarrhea vs. placebo (absolute risk reduction = 3.5%; number needed to treat = 29) ⁵³. This review did not find a significant difference in Clostridium difficile infection with probiotics compared with placebo ⁵³. A meta-analysis of 20 randomized controlled trials with 3,818 adults and children demonstrated a significantly decreased risk of Clostridium difficile–associated diarrhea (number needed to treat = 30) ⁵⁴. A meta-analysis of two low-quality randomized controlled trials including 495 children and adults found no significant effect of yogurt vs. placebo to prevent antibiotic-associated diarrhea ⁵⁵.

Helicobacter pylori infection

There are inconsistent results on the effectiveness of probiotics as an adjunct to antibiotic therapy to improve Helicobacter pylori eradication rates. A meta-analysis of nine randomized controlled trials involving 1,163 children and adults found that using Lactobacillus-containing probiotics as an adjunct to antibiotics increased the H. pylori eradication rate compared with control (number needed to treat = 10) ⁵⁶. However, a meta-analysis of 21 randomized controlled trials with 3,452 adults found that probiotics as an adjunct to antibiotics did not improve the eradication of H. pylori infection (odds ratio = 1.44) compared with placebo ⁵⁷.

Allergic diseases

The potential immunomodulatory effects of Lactobacillus rhamnosus GG that have yet received most attention include its widely discussed effects against allergic disease. In a study published in The Lancet, Kalliomäki and colleagues ⁵⁸, ⁵⁹, ⁶⁰ showed that the combination of prenatal maternal (2-4 weeks) and postnatal pediatric (6 months) Lactobacillus rhamnosus GG treatment (10¹⁰ CFU daily, capsules or in water) in families with a history of atopic disease, significantly lowered the risk of eczema at the age of 2, 4 and 7. However, allergic rhinitis and asthma tended to be more common in the Lactobacillus rhamnosus GG treated group and no significant differences were found in incidence of cow milk allergy. Moreover, Kopp and colleagues ⁶¹ could not repeat the beneficial results against eczema using a similar protocol and concentration. The reason for these different outcomes is unknown, however it is thought that the different genetic background of the tested populations (Finnish versus German) might play a role. Also, the German trial had more infants with older siblings, which could be a potential cofounder ⁶¹. In addition, it seems that different probiotic products have been used for these studies, so that also differences in probiotic formulation, and for instance pili presence, cannot be ruled out.

Atopic dermatitis in children could not be treated by Lactobacillus rhamnosus GG in three independent trials, using a daily concentration of 5×10⁹ CFU/100 ml formula ⁶², 5×10⁹ CFU in milk ⁶³ or 10¹⁰ CFU in milk ⁶⁴. However, in these trails there was a consistent but not significant effect of Lactobacillus rhamnosus GG in the IgE-sensitized subgroup. Two other trials also reported that treatment (5×10⁹ CFU daily in milk) was efficient in IgE-sensitized infants, but not in non-IgE-sensitized infants ⁶⁵, ⁶⁶. This is probably a good example that patient stratification is important to identify potential responders, but more research is necessary to determine the effect of Lactobacillus rhamnosus GG in IgE-sensitized infants.

Related to food allergy, it was reported that administration of capsulated Lactobacillus rhamnosus GG (5×10⁹ CFU) in infants with cow’s milk allergy augments IFN-γ production in stimulated peripheral blood mononuclear cells, thus possibly providing beneficial TH1 immunomodulatory signals ⁶⁶. Infants acquire more oral tolerance when hydrolyzed casein formula was administered in combination with Lactobacillus rhamnosus GG (10⁷ CFU/ 100 mL) than with the formula alone ⁶⁷. In milk-hypersensitive adults, Lactobacillus rhamnosus GG (2.6×10⁸ CFU daily in milk) has been shown to reduce the immunoinflammatory response by reducing the expression of specific receptors such as the complement receptors CR1 and CR3 ⁶⁸.

Lactobacillus rhamnosus administration in cancer patients

The most important effect of Lactobacillus rhamnosus GG, observed in cancers patients is linked to the reduction of acute or chronic diarrhea associated with chemotherapy and radiotherapy in cancer patients ⁶⁹. Diarrhea affects the quality of life of patients as well as the anti-cancer treatment efficacy. Such patients experiencing diarrhea cannot tolerate the standard dose of therapy and need many adjustments in its dose and frequency. This side effect may also require hospitalization caused by the electrolytes loss. Acute or chronic diarrhea is observed among cancer patients treated with pelvic radiation therapy and/or with common antineoplastic agents. In detail, microvascular apoptosis and sclerosis of the vessels may occur during radiation therapy as results radiation-induced gut toxicity ⁷⁰; while direct epithelial damage may be produced by chemotherapy ⁷¹. Drugs used to stop diarrhea, such as loperamide, were not useful to restore the gut microflora. While the appropriate use of probiotics has been shown to be active and safe ⁶⁹. For instance, Osterlund et al. ⁷² reported interesting results in the phase 3 randomized study on cancer patients. The authors considered the combination of radio- and chemo-therapy and radiation therapy alone. The Lactobacillus rhamnosus GG was administered as 1–2 capsules/die (10¹⁰ CFU) for 24 weeks during any anti-cancer treatment. The reports for diarrhea episode of grades 3 and 4 were 15% lower for those receiving Lactobacillus rhamnosus GG than the control group, suggesting that Lactobacillus rhamnosus GG supplementation may be a well-tolerated product able to ameliorate the compliance to the common cancer therapies ⁷².

Recently a meta-analysis of 11 randomized and placebo controlled studies evaluating the efficacy and safety of probiotics for prevention of chemo- and radiotherapy-induced diarrhea in people with abdominal and pelvic cancer was published. The study reported a potential beneficial effect of probiotics in the prevention of chemoradiotherapy-induced diarrhea with rare adverse events ⁶⁹.

Lactobacillus rhamnosus GG as a vaccine adjuvant

Another perhaps more elegant way to investigate the immunomodulatory effects of Lactobacillus rhamnosus GG is by studying its capacity to ameliorate humoral responses to vaccines when applied as an adjuvant. One study showed that the immunogenicity of an oral rotavirus vaccine was significantly ameliorated when mixed with 5×10¹⁰ CFU of Lactobacillus rhamnosus GG ⁷³. Lactobacillus rhamnosus GG in milk (10¹⁰ CFU daily, 1 week before vaccination, 4 weeks after) was also shown to increase the poliovirus neutralizing antibody titer with a fourfold increase in poliovirus-specific IgA in adults receiving an oral vaccine against polio 1, 2 and 3 ⁷⁴. Moreover, Lactobacillus rhamnosus GG treatment (10¹⁰ CFU in a capsule, daily, 28 days starting at vaccination) increased protection rates after an oral life attenuated influenza vaccine. The effect was viral strain-dependent as antibody titers against H1N1 and B strains were low for placebo and Lactobacillus rhamnosus GG-treated groups. For the H3N2 strain, Lactobacillus rhamnosus GG increased protection significantly ⁷⁵. However, there was no influence on the effect of an oral Salmonella Typhi Ty21a oral vaccine (4×10¹⁰ CFU daily, 7 days) ⁷⁶. In addition, a recent study even showed that maternal supplementation with Lactobacillus rhamnosus GG (1.8 × 10¹⁰ CFU daily) from 36 weeks gestation until delivery reduces vaccine-specific immune responses for tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7) vaccines in infants at high risk of developing allergic disease ⁷⁷, indicating that the timing of administration is important if one desires an adjuvant effect and that Lactobacillus rhamnosus GG might not always be the best choice for these purposes. Moreover, van Baarlen et al. ⁷⁸ showed other lactobacilli such as Lactobacillus plantarum WCFS1 show a more clear modulating of the NF-κB pathway.

Lactobacillus rhamnosus dosage

A Cochrane review found that a dosage of 5 billion colony-forming units or greater per day was significantly more effective than a lower dosage ⁴⁹. However for disease specific dosage see Lactobacillus rhamnosus benefits section above.

• Usual adult dose for general use as dietary supplement is 1 capsule per day
• Usual adult dose for general use concurrently with antibiotics is 1 capsule twice a day throughout antibiotic therapy and for one week after antibiotic therapy
• Usual adult dose for general use for traveling is 1 capsule twice daily throughout the trip. It is best to start 2 to 3 days prior to travel.
• Usual Pediatric Dose for Dietary Supplement is one-half to one capsule per day. Open the capsule and stir the contents into a cool drink or mix into baby food or applesauce.

Lactobacillus rhamnosus side effects

The use of Lactobacillus rhamnosus GG in a wide variety of clinical trials without serious adverse events confirmed its safety. Common side effects of Lactobacillus rhamnosus may include stomach bloating or gas. Lactobacillus rhamnosus GG has been administered to, among others, low birth weight infants ⁷⁹, pregnant women ⁸⁰, HIV- infected patients ⁸¹ and patients with a mechanical ventilator ⁴¹. To support the safety of Lactobacillus rhamnosus GG, it was shown that despite increasing Lactobacillus rhamnosus GG consumption in Finland and Sweden respectively, the rate of Lactobacillus bacteremia remained constant ⁸².

However, case reports show that probiotic therapy is to be discouraged in certain groups of patients. In a review concerning the safety of probiotics, it was concluded that adverse effects of probiotics were correlated with (i) impaired intestinal barrier function, (ii) immune compromised state and (iii) central venous catheter ⁸³. Indeed, cases specifically reported for Lactobacillus rhamnosus GG show that these risk factors might play a role. For instance, a number of infants treated with Lactobacillus rhamnosus GG for short gut syndrome associated with intestinal friability seemed to manifest sepsis with Lactobacillus rhamnosus GG-like bacteria ⁸⁴ and an ulcerative colitis patient was diagnosed with Lactobacillus rhamnosus GG bacteremia ⁸⁵, although these identifications were not done at a detailed genomic level. Nevertheless, in patients with a seriously compromised integrity of the barrier function of the intestine, the administration of specific Lactobacillus rhamnosus GG molecules is probably a better strategy than living Lactobacillus rhamnosus GG cells, because of the risk for translocation of the bacteria from the intestines into the blood ². The long-term effects of probiotics are largely unknown, and additional randomized trials are needed to address this question ⁸⁶.

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