The medical treatment of schizophrenia or depression is effective to varying degrees; however, it is associated with potentially serious side effects, particularly weight gain. Remedial strategies have been tested, including the use of probiotics to prevent or reduce unwanted weight gain in these patients. A recent study published in Translational Psychiatry discusses the effectiveness of probiotics and their use in reducing medication-induced weight gain.
The link between weight gain and mental illness
Severe mental illnesses are associated with abnormal weight gain, leading to a higher risk of obesity and associated metabolic disorders. This includes high cholesterol and sugar levels, both risk factors for cardiovascular disease (CVD). Obesity is also associated with an increased risk of cancer, diabetes, and fatty liver disease. Additionally, this condition often leads to poor compliance with medication protocols. While these risk factors may decrease the risk of metabolic complications, they also increase the likelihood that the patient will relapse or experience a worsening of their psychiatric disorder. The consequence could be a chronic psychiatric illness with lower quality of life and a shorter lifespan. Possible reasons for weight gain in mentally ill individuals may include low physical activity combined with poor eating habits, both of which contribute to unhealthy weight gain. Furthermore, antidepressants and antipsychotic medications are among the most common categories of psychopharmacological drugs, both of which lead to increased appetite, weight gain, and metabolic syndrome. The effect of these medications on brain circuits may increase a person’s appetite or decrease microbial diversity in the gut. Previous studies have shown that weight gain and cardiovascular damage are associated with lower gut microbial diversity. These effects cannot be easily corrected by reducing overall calorie intake or increasing exercise, unless the microbiome is also improved, as the available intake of food can be used more efficiently and stored with this abnormal microbial profile.
Mental health and the gut microbiome
Mental disorders often come with abnormal microbial patterns, such as fewer bacteria producing short-chain fatty acids (SCFAs), an increased number of lactic acid producers, and bacteria driving the metabolism of glutamate and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In patients with schizophrenia, genera Prevotella are more common, while Bacteroides and Haemophilus are present in lower amounts. Conversely, in depression, Alistipes and Parabacteroides are often more common and Prevotella values are lower. The lower the values of Clostridia and Firmicutes, the more severe the depression is likely to be. These effects may be partly attributed to the antibiotic effect of certain medications used in psychiatry, weight gain, or insulin resistance. In contrast, probiotics have been shown to improve metabolic parameters in obese individuals.
What did the study find?
In the current study, researchers reviewed studies published up to June 15, 2022, including patients with depression or schizophrenia, and investigated how weight measurements, metabolic parameters, and gut microbiota are related to the use of probiotics. Four of the reviewed studies used a probiotic formulation containing: Bifidobacterium, Lactobacillus, and Enterococcus, which were used in various combinations, all of which were well tolerated. In two studies using probiotics, the benefit of these agents in relieving weight gain due to the consumption of psychopharmacological drugs could not be demonstrated. One study included a composition of live-study Lactobacillus acidophilus, Bifidobacterium longum, and Enterococcus faecalis. Despite an initial reduction in weight gain, no differences were observed between the intervention and control groups. Another study used a combination of Bifidobacterium bifidum, longum and lactis, and Lactobacillus acidophilus; however, no difference in weight gain was observed. However, certain metabolic markers improved in the intervention group, along with reduced inflammation, as demonstrated by lower C-reactive protein (CRP) levels in the blood. Two studies used synbiotics, a combination of probiotics and prebiotics. These individuals did not experience as much weight gain as those treated otherwise. Interestingly, psychiatric health improved significantly in the intervention group during the study period. In one study, adding selenium to the probiotics boosted the extent of improvement. In another study, the gut microbiome was examined, and the addition of both fibers and probiotics changed the composition of the gut microbiome.
What are the implications?
The use of synbiotics led to less weight gain with better metabolic markers. This could be attributed to a change in the gut microbiome profile that processes food in a healthier way. Manipulating the diet may help reduce weight gain caused by psychopharmacological drugs. However, the effect may be enhanced by synbiotics. Augmenting with this combination during the use of psychopharmacological drugs could be a promising approach for further investigation. Due to the high tolerability and acceptance of probiotics, as well as their potential benefits in mental illnesses, they are commonly used as dietary supplements for mentally ill patients in treatment, particularly because they do not interfere with the effects of psychopharmacological drugs. Further research is needed to investigate the mechanisms by which synbiotics affect intestinal bacteria, weight gain, and metabolic dysregulation, as well as interindividual differences in the baseline and probiotic or medicinally altered gut microbiome. Chronic psychiatric illnesses should also be considered in future studies, as these pose a risk factor for side effects.
Journal Reference: Motteli, S., Vetter, S., Colla, M. & Hotzy, F. (2024). Are probiotics effective in reducing the metabolic side effects of psychopharmacological drugs? A comprehensive review of evidence from clinical studies. Translational Psychiatry. doi:10.1038/s41398-024-02735-z.