Probiotics for ‘chemo brain’

Affordable and convenient probiotics may help prevent cancer-related cognitive impairment.

Chemotherapy-induced cognitive impairment or cancer-related cognitive impairment is also commonly termed “chemo brain” or “chemo fog”. The functions most impacted are memory, complex attention and processing speed.^1,2 These complications are becoming more concerning for people, as the number and life expectancy of cancer survivors are increasing due to, for example, better cancer screening 

Unfortunately, the mechanism(s) that cause chemotherapy-induced cognitive impairment are not well understood, so management options are limited.^1,2

Current management options are largely behavioural interventions that serve as a compensatory strategy for dealing or coping with the cognitive issues – for example, relaxation, cognitive rehabilitation (occupational therapy), brain-training programs and psychoeducation.¹ Other options look to optimise factors that can lead to subjective improvements, such as exercise, diet, sleep and reducing stress.¹ Pharmacological management – for example, modafinil and methylphenidate (central nervous system stimulants) or donepezil (acetylcholinesterase inhibitor) – has little evidence to support its use and is highly person-specific.¹

There is increasing work that proposes a link between gut microbiota with brain structure and function. Furthermore, dysbiosis of the gut microbes reportedly may lead to development of psychiatric and neurodegenerative conditions, which can be alleviated by probiotic supplementation that reduces the imbalance of the gut microflora.²

‘Probiotics are live, non-pathogenic yeasts or bacteria’,³ that when administered in adequate amounts, ‘confer a health benefit on the host’.⁴ These benefits are strain- and disease-specific, so effects reported for one preparation may not apply to another.^3,5 The use of probiotics is commonly associated with preventing and/or helping with conditions such as atopic dermatitis, or gut issues such as irritable bowel syndrome.⁵

Since chemotherapy also reportedly disrupts the gut microflora and triggers neuroinflammation, researchers set out to investigate whether probiotic supplementation would be of any benefit for chemotherapy-related cognitive impairment. A randomised, double-blinded, placebo-controlled study design was implemented, involving 159 patients with breast cancer (Stages I–III). In addition to standard chemotherapy, three probiotic capsules were taken twice daily, with each containing Bifidobacterium longum (≥1.0 x 10⁷ CFU/210 mg), Lactobacillus acidophilus (≥1.0 x 10⁷ CFU/210 mg) and Enterococcus faecalis (≥1.0 x 10⁷ CFU/210 mg).²

Compared to the placebo (n = 79), the probiotics group (n = 80) scored significantly better on most of the measures for the chemotherapy-related cognitive impairment. The incidence of chemotherapy-related cognitive impairment (primary outcome) was significantly lower in the probiotics group compared to placebo (35% vs 81%); with a relative risk of 0.43 (95% confidence interval = 0.34–0.51).²

Of the secondary outcome measures, no significant difference was noted with anxiety, depression, blood cell counts, liver and kidney function. However, at the time point of chemotherapy completion, probiotic supplementation significantly reduced blood glucose and low density lipoprotein (LDL) levels, changed (‘normalised’) faecal microbiota compositions, and modulated plasma metabolite changes.² A number of these metabolites were found to be negatively correlated with the occurrence of chemotherapy-related cognitive impairment. Further work in rats found probiotic supplementation to increase levels of one of these metabolites (p-Mentha-1,8-dien-7-ol), and exogenous administration of which significantly reduced ‘chemotherapy-induced long-term potentiation impairment, synapse injury, oxidative stress and glial activation in the hippocampus’.²

The findings from this study are exciting because if something as affordable and convenient as probiotic supplementation can help prevent the development of chemotherapy-induced cognitive impairment, it would make a world of difference to people receiving chemotherapy treatment. The authors have heralded the findings from this study as ‘proof of concept’, and more work is certainly required to better understand the use of different probiotics with different chemotherapy treatments, and in more diverse and larger cohorts of people – particularly given variations in gut microbiota (for example, due to differences in people’s genetics, environmental exposure and dietary choices).² Similarly, further insight into the relationship between changes in gut microbiota, and blood metabolites, blood glucose and LDL levels on chemotherapy- related cognitive impairment, would help with better understanding the clinical utility of probiotics in this space.

References 

1. Meadows M-E. Cognitive function after cancer and cancer treatment. Waltham (MA): Wolters Kluwer; 2023.
2. Juan Z, Chen J, Ding B, et al. Probiotic supplement attenuates chemotherapy-related cognitive impairment in patients with breast cancer: a randomised, double-blind, and placebo-controlled trial. Eur J Cancer 2022;161(2002):10–22.
3. Australian Medicines Handbook. Australian Medicines Handbook – Probiotics: Australian Medicines Handbook Pty Ltd; 2022.
4. Hill C, Guarner F, Reid G, et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11(8):506–14.
5. National Institutes of Health Office of Dietary Supplements. Probiotics fact sheet for health professionals Maryland (US): National Institutes of Health Office of Dietary Supplements; 2022 At: https://ods.od.nih.gov/factsheets/Probiotics-HealthProfessional/