Researchers publishing in Probiotics and Antimicrobial Proteins have published the results of a clinical trial on the effects of a probiotic on inflammaging in older people.
The gut and systemic inflammation
The researchers begin this paper discussing their target of inflammaging, as this condition has been linked to multiple other age-related disorders, including Alzheimer’s [1]. Inflammaging has been found to have multiple causes, one of them being a change in gut bacteria [2]. The intestinal bacteria’s gradual transition from a younger to an older phenotype has been well-documented [3], but strategies for re-colonizing the human gut with probiotics have only been somewhat explored, with one trial demonstrating effectiveness against the age-related muscle loss known as sarcopenia [4].
Therefore, these researchers decided to perform a clinical trial of probiotics against inflammaging, with the endpoints being biomarkers of inflammation such as C-reactive protein (CRP). Because some compounds naturally found in berries have been previously found to have antioxidant [5] and anti-inflammatory [6] properties, berries were also included to determine if their effects could be complementary to probiotics.
Largely inconclusive results with bright spots
An active version of Lactiplantibacillus plantarum HEAL9 (LpHEAL9) was chosen as the probiotic for this study. Out of 187 screened subjects, 66 people had enrolled into it, with 22 being allocated to each group: placebo control, LpHEAL9, and LpHEAL9 with berries. The participants were all in their seventies, with a mean age of 73.2.
Unfortunately, this study did not meet its CRP endpoint. While there was a trend towards decreasing CRP in the LpHEAL9-only group, this result did not meet statistical significance, and other results also trended similarly. However, the LpHEAL9-only group had less of the inflammatory biomarker calprotectin in their feces, and this result was statistically significant. This group also appeared to have less of the inflammatory factor TNF-alpha, although this result did not quite reach statistical significance, and there were no differences in other serum biomarkers.
Some positive trends were found in cognition. The LpHEAL9-only group had trends towards better performance on one of the cognitive trail-making tests compared to either of the other groups, and the berries-included group appeared to perform slightly better on the other test; these results, too, did not reach statistical significance.
When examining a variety of other metrics, the researchers found a beneficial, statistically significant result in body pain, which was decreased in the group that included berries. There was also a harmful result: while over the course of the study, the systolic blood pressure of the placebo group was significantly reduced, this occurred to neither of the LpHEAL9 groups. Many other metrics, including most gastrointestinal metrics, did not have any statistically significant results. The bowel function of the LpHEAL9-only group was disrupted for the first three weeks, with an increase in bowel movements, but this returned to normal over time.
While these results are largely disappointing and suggest a lack of efficacy for this probiotic treatment against inflammaging-related conditions, the calprotectin result suggests that there are potential uses for LpHEAL9. In a previous study, a different strain of this bacterium, CJLP243, was also found to reduce calprotectin, and this significantly reduced diarrhea in a population that had elevated levels of this biomarker [7]. Calprotectin is also a key biomarker in determining inflammatory from non-inflammatory bowel syndromes [8].
These largely mixed results suggest that berry supplementation, in addition to probiotics, may be useful in decreasing overall pain, although this result will have to be confirmed with a separate study. While this particular probiotic may not be effective against inflammaging in general, this or other probiotics may be useful in treating inflammatory gut conditions.
Literature
[1] Franceschi, C., Bonafè, M., Valensin, S., Olivieri, F., De Luca, M., Ottaviani, E., & De Benedictis, G. (2000). Inflamm‐aging: an evolutionary perspective on immunosenescence. Annals of the new York Academy of Sciences, 908(1), 244-254.
[2] Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023). Inflammation and aging: signaling pathways and intervention therapies. Signal Transduction and Targeted Therapy, 8(1), 239.
[3] Mariat, D., Firmesse, O., Levenez, F., Guimarăes, V. D., Sokol, H., Doré, J., … & Furet, J. (2009). The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC microbiology, 9, 1-6.
[4] Qaisar, R., Burki, A., Karim, A., Iqbal, M. S., & Ahmad, F. (2024). Probiotics supplements Improve the sarcopenia-related quality of life in older adults with age-related muscle decline. Calcified Tissue International, 114(6), 583-591.
[5] McGhie, T. K., Walton, M. C., Barnett, L. E., Vather, R., Martin, H., Au, J., … & Kruger, M. C. (2007). Boysenberry and blackcurrant drinks increased the plasma antioxidant capacity in an elderly population but had little effect on other markers of oxidative stress. Journal of the Science of Food and Agriculture, 87(13), 2519-2527.
[6] Landete, J. M. (2011). Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health. Food research international, 44(5), 1150-1160.
[7] Jung, M., Jung, S., Kim, N., Ahn, H., Yun, H., & Kim, K. N. (2022). A randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of Lactiplantibacillus plantarum CJLP243 in patients with functional diarrhea and high fecal calprotectin levels. Nutrients, 14(2), 389.
[8] Menees, S. B., Powell, C., Kurlander, J., Goel, A., & Chey, W. D. (2015). A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS. Official journal of the American College of Gastroenterology| ACG, 110(3), 444-454.
