Written by Taylor Woosley, Staff Writer. Two-month co-supplementation of inulin and L. rhamnosus significantly reduced hs-CRP (p=0.020) and TNF-α (p=0.032) levels in subjects, while also decreasing scores relating to the Beck Depression Inventory (p=0.001). 

depressed womanCoronary artery disease (CAD) is one of the most common cardiovascular illnesses and is the leading cause of death globally1. Depression and anxiety disorders are frequently associated with CAD, with chronic inflammation thought to contribute to the etiopathogenetic process of depression and atherosclerosis2. The pathophysiological mechanism underlying the association between depression and heart disease have not been proven, but there is evidence that endothelial dysfunction inflammatory activation and neuroendocrine dysregulation in depression might mediate the increased risk3. Additionally, disruptions to the gut microbiome have been correlated with several neuropsychiatric disorders, including depression4.

The use of prebiotics and probiotics have garnered substantial interest of late to produce beneficial effects on health without the addictive properties of several currently available treatments for those with depression5. Probiotics are preparations of microorganisms that can improve gut microbial balance, while prebiotics are nondigestible compounds that are metabolized by gut microorganisms to ultimately benefit the host6. The composition of the intestinal flora in patients with depression differs from that in healthy people, which may be the result of elevated levels of oxidative stress and inflammatory processes which increases levels of pro-inflammatory cytokines like IL-6 and TNF-α7. Past research has shown that use of prebiotics and probiotics can suppress inflammation and modulate the immune system, as well as reduce intestinal permeability8.

Moludi et al. conducted a double-blind, four-arm parallel randomized controlled trial to evaluate the effects of inulin (prebiotic), the probiotic (L. rhamnosus), and their co-administration on the Beck Depression Inventory (BDI) score, anxiety, and quality of life (QOL), as a primary outcome. Additionally, secondary outcomes included chronic inflammation and endotoxemia in adults with CAD. Subject inclusion consisted of being between 18-85 years old with CAD. Study exclusion included having a medical history of using immunosuppressive or anti-inflammatory drugs and a history of using pre- or pro-biotics at least two months prior.

Subjects (n=96) were randomly allocated to one of four groups: (1) prebiotic group (one sachet containing 15 g inulin per day) (n=24), (2) probiotic group (one capsule contained 1.9 x 109 colony-forming unit (CFU) of L. rhamnosus per day) (n=24), (3) co-supplemented group (both inulin and L. rhamnosus) (n=24), (4) placebo group (a sachet and a capsule filled with maltodextrin) (n=24). Phone calls were made every two weeks to confirm study compliance and the intervention was taken for two months. Dietary intake was assessed using a 24-hr recall at weeks 0 and 8 of intervention. Blood samples were collected after 12 hours of fasting to test for interleukin (IL)-10, tumor necrosis factor-alpha (TNF-α), and lipopolysaccharides [(LPS), a marker of gut permeability] using enzyme-linked immunosorbent assay (ELISA) kits. Further measurements such as high sensitivity (hs-CRP) levels, lipid profiles, and fasting blood sugar were also obtained. The Beck Depression Inventory-II (BDI-II) was used to categorize patients into two groups: depressed or non-depressed. QOL was measured using the MacNew questionnaire and anxiety was measured by Spielberger state-trait anxiety inventory form Y (STAI-Y).

After the invention, ANCOVA analysis was used to compare the four groups’ differences and adjusted confounders and baseline biomarkers/psychological questionnaires using Sidak’s method. There was no statistically significant difference in the history of depression, sex, physical activity, and education levels in the four study groups (p>0.05). Significant findings of the study are as follows:

  • Regarding inflammatory markers, after adjustment for baseline levels and confounding factors, a significant reduction in LPS and TNF-α levels in the probiotic group compared with placebo was noted (p=0.014, p=0.030, respectively).
  • The probiotic-inulin co-supplementation significantly decreased serum hs-CRP (−1.69 ± 0.66 vs. +0.82 ± 0.39 mg/dL, P = 0.020), LPS (−22.02 ± 5.40 vs. +0.31 ± 0.18 (EU/L), P = 0.047), and TNF-α (−25.05 ± 7.41 vs. +0.79 ± 0.71 (ng/L), P = 0.032) concentration compared to placebo.
  • BDI and STAI-trait scores significantly decreased in probiotics groups (p=0.001, p=0.006, respectively) compared to baseline. Furthermore, adding inulin to the probiotic amplified the improvement of psychological outcomes more than either the prebiotic or probiotic alone. The probiotic-inulin co-supplementation significantly decreased BDI (−11.52 ± 0+3.2 vs. +2.97 ± 0.39, P = 0.001), STAI-state (−17.63 ± 3.22 vs. −0.60 ± 0.33 mmol/L, P = 0.021), and STAI-trait (−24.31 ± 7.41 vs. −1.45 ± 0.66, P = 0.020) scores compared to placebo.

Significant results of the study show that co-supplementation of inulin and L. rhamnosus decreased inflammatory markers, depression scores, and anxiety scores in CAD patients. Further research should continue to explore the use of prebiotics and probiotics to improve inflammation and depression scores in subjects. Study limitations include the short intervention period and lack of information and testing around gut microbiota analysis.

Source: Moludi, Jalal, Hamed Khedmatgozar, Seyed Mostafa Nachvak, Hadi Abdollahzad, Mehdi Moradinazar, and Ali Sadeghpour Tabaei. “The effects of co-administration of probiotics and prebiotics on chronic inflammation, and depression symptoms in patients with coronary artery diseases: a randomized clinical trial.” Nutritional neuroscience 25, no. 8 (2022): 1659-1668.

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Posted December 1, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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