The probiotic LGG works by making resident gut bacteria produce anti-inflammatory products.

How do probiotics work? Do they do anything or am I flushing money down the toilet? Lactobacillus rhamnosus GG (LGG), one of the most common probiotics available, can improve a variety of digestive disorders [1, 2], psychiatric disorders [3], and atopic dermatitis [4] in infants and children. LGG does not “move in” and establish residence in the gut [5]. It simply passes through. Findings from this study by Eloe-Fadrosh et al. suggests that probiotic bacteria may not need to take up residence in the human gut to be helpful, but that these effects are variable among individuals.

Gut microbiome diversity in elderly patients during LGG probiotic study.
Gut microbiome diversity in elderly patients during LGG probiotic study. Bacterial community diversity did not significantly change in the presence of the probiotic (Day 28). PD = phylogenetic diversity. For additional details see original paper: Eloe-Fadrosh, et al, 2015. MBio

Claire Fraser’s research group at the University of Maryland, Institute for Genome Sciences and colleagues at the Massachusetts General Hospital for Children examined samples from an open label study (people knew they were taking a probiotic) to assess safety of the probiotic LGG [6] in healthy, elderly patients. Fecal samples of 12 healthy adults (7 females and 5 males) ages 65 to 80 were collected prior-to, during, and one month after taking the LGG probiotic twice daily. The number of different types of bacteria and genetic activity of the microbiome was compared within and between individuals across time.

So why and how does the probiotic LGG work when it doesn’t stay in the gut? LGG seems to increase the activity of the genes for movement and adhesion in helpful gut bacteria that already reside in the gut [7]. In the presence of LGG, the helpful bacteria, increase their movement and stickiness to the gut, and produce anti-inflammatory compounds, including butyrate. Butyrate is an important short-chain fatty acid produced by bacteria that feeds human colon cells, has anti-inflammatory properties [8], and makes it easier for helpful bacteria to penetrate the human gut mucus lining. The resident gut microbiome gene activity increased when patients were taking the probiotic. When the probiotic was stopped, the gene activity it increased also stopped.

Gene activity levels increase while LGG is consumed. Profiles of 4 individuals over the course of the study: before, during, and after the probiotic LGG.
Gene activity levels increase while LGG is consumed. Profiles of 4 individuals over the course of the study: before, during, and after the probiotic LGG. The heights of the bars represent amount of gene activity. Different bar color represents the particular genes. For additional information see the original paper Eloe-Fadrosh, et al. 2015 mBio

This study also found that the response to LGG varied between people. Differences in gene activity between people suggest that context matters. Different human genomes or microbiome communities may influence probiotic benefits. Environmental influences, such as human host diet and exercise, could also change probiotic activities. That finding in itself may explain why the results of probiotics both in clinical trials and personal experiences are so varied. As has been found in other studies, a patient’s digestive system microbiome diversity was specific to that person [9, 10]. Patients could be identified by their unique bacterial strains, which was a novel finding of this study [7]. Non-bacterial members of the microbiome also were found to contribute to the genetic activity in one group of patients, suggesting that other microbes may be important in the digestive system microbiome.

So how does LGG work? The bottom line is that it may trigger the helpful bacteria already present in your gut to make chemicals that are beneficial to your gut health. It depends on what your current microbiome community is and perhaps your genetic makeup. When thinking of restoring a disrupted microbiome, we generally think of adding helpful bacteria back to our disturbed ecosystem to restore a balance. Think about eating yogurt after taking antibiotics or why the fermented food movement has generated so much attention. You are thought to be reseeding your beneficial bacterial garden after hoeing out the “weeds”. But perhaps probiotics may also benefit by interacting with the resident microbiome. In another gardening analogy – perhaps it’s like beneficial insects that pollinate the plants. These insects may not take up residence in the garden, but they interact in a helpful way to the garden ecosystem.

Like all ecosystems, whether between macroorganisms or microorganisms, interactions between the residents and transients are key. Certainly, we at only at the beginning in understanding how probiotics function in the dynamic and complex human digestive system microbiome.

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REFERENCES

  1. Sindhu, K. N. C., T. V. Sowmyanarayanan, A. Paul, S. Babji, S. S. R. Ajjampur, S. Priyadarshini, R. Sarkar, K. A. Balasubramanian, C. A. Wanke, H. D. Ward, et al. 2014. Immune Response and Intestinal Permeability in Children With Acute Gastroenteritis Treated With Lactobacillus rhamnosus GG: A Randomized, Double-Blind, Placebo-Controlled Trial. Clinical Infectious Diseases 58:1107-1115.
  2. Pärtty, A., R. Luoto, M. Kalliomäki, S. Salminen, and E. Isolauri. 2013. Effects of Early Prebiotic and Probiotic Supplementation on Development of Gut Microbiota and Fussing and Crying in Preterm Infants: A Randomized, Double-Blind, Placebo-Controlled Trial. The Journal of Pediatrics 163:1272-1277.e2.
  3. Partty, A., M. Kalliomaki, P. Wacklin, S. Salminen, and E. Isolauri. 2015. A possible link between early probiotic intervention and the risk of neuropsychiatric disorders later in childhood – a randomized trial. Pediatr Res.
  4. Foolad, N., E. A. Brezinski, E. P. Chase, and A. W. Armstrong. 2013. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids. JAMA Dermatol 149:350-5.
  5. Ismail, I. H., F. Oppedisano, S. J. Joseph, R. J. Boyle, R. M. Robins-Browne, and M. L. K. Tang. 2012. Prenatal administration of Lactobacillus rhamnosus has no effect on the diversity of the early infant gut microbiota. Pediatric Allergy and Immunology 23:255-258.
  6. Hibberd, P. L., L. Kleimola, A.-M. Fiorino, C. Botelho, M. Haverkamp, I. Andreyeva, D. Poutsiaka, C. Fraser, G. Solano-Aguilar, and D. R. Snydman. 2014. No Evidence of Harms of Probiotic Lactobacillus rhamnosus GG ATCC 53103 in Healthy Elderly—A Phase I Open Label Study to Assess Safety, Tolerability and Cytokine Responses. PLoS ONE 9:e113456.
  7. Eloe-Fadrosh, E. A., A. Brady, J. Crabtree, E. F. Drabek, B. Ma, A. Mahurkar, J. Ravel, M. Haverkamp, A.-M. Fiorino, C. Botelho, et al. 2015. Functional Dynamics of the Gut Microbiome in Elderly People during Probiotic Consumption. mBio 6.
  8. Furusawa, Y., Y. Obata, S. Fukuda, T. A. Endo, G. Nakato, D. Takahashi, Y. Nakanishi, C. Uetake, K. Kato, T. Kato, et al. 2013. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504:446-450.
  9. Segata, N., S. Haake, P. Mannon, K. Lemon, L. Waldron, D. Gevers, C. Huttenhower, and J. Izard. 2012. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biology 13:R42.
  10. Costello, E., C. Lauber, M. Hamady, N. Fierer, J. Gordon, and R. Knight. 2009. Bacterial community variation in human body habitats across space and time. Science 326:1694 – 1697.

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