also other central nervous system (CNS)
molecules that are implicated in th...
markers such as inflammatory cytokines.
Yet, it is important to note that w...
of 2

Polina Kapoustina 1st student scholarship

Published on: Mar 4, 2016

Transcripts - Polina Kapoustina 1st student scholarship

  • 1. NATUROPATHIC DOCTOR NEWS & REVIEWFebruary 2014 also other central nervous system (CNS) molecules that are implicated in the pathophysiology of depression. Desbonnet et al3 showed that Bifidobacteria infantis could modulate tryptophan metabolism, suggesting that the normal gut microflora can influence the precursor pool for serotonin (5-HT), a major neurotransmitter of the brain-gut axis and mood. Furthermore, by investigating behavior and brain mRNA expression of genes implicated in anxiety and stress reactivity, another study4 found that germ-free mice exhibited decreased serotonin receptor 1A (5HT1A) expression, which normally binds 5-HT, in the hippocampus. This research suggests that probiotics can affect mood chemistry and susceptibility to anxiety and depression at the CNS level. Probiotics not only affect mood and anxiety behavior in the long term, but also acutely; in fact, such behavior is observed as early as 7 to 8 hours after infecting mice with a gut pathogen.5 Possible mechanisms may be via the vagus nerve and enteric nervous system (ENS), as well as various inflammatory cytokines and hormones.6 It is interesting to note that stress is at the root cause of these physiological changes seen in anxiety. Chronic stress overload can lead to both gastrointestinal and mood disorders by disrupting the microflora balance.7 Yet, depression itself will also reduce one’s ability to cope with any sort of stress, and so the vicious cycle continues. The brain- gut axis is even more evidenced by the fact that 50% of irritable bowel disease (IBD) patients also present with mood disorders.8 Similarly, there have been positive results using antidepressants to treat IBD.9 Hence, the animal data suggests a bidirectional communication between the gut and the brain. The type of stress will be unique to each individual, and naturopathic doctors have an important role to play in helping patients identify it. Human Clinical Trials Clinical research has demonstrated evidence for probiotics as a preventive and adjuvant therapy for improving general mental health in both patients with stress-related psychiatric conditions and healthy subjects. The most recent research was presented at a conference session given by Tillisch in 2012.10 Tillisch discussed evidence that demonstrated diminished brain arousal in healthy women while taking probiotics and performing emotional tasks over a 4-week period (see Table 1). The diminished connectivity of the amygdala-centered network within the cortex suggests a role for probiotic supplementation in manipulating brain activity. Messaoudi et al performed 2 double- blind studies in 2011 examining the effect of probiotics on stress reactions. In the first study,11 healthy subjects with low stress were divided into probiotic and placebo groups. After 30 days, participants in the probiotic group showed improvements in mood, as measured through various stress scales, as well as lower urinary free cortisol (see Table 1). Messaoudi’s follow-up study12 further showed that even the least stressed subjects benefited from probiotics, as measured by lower scores on anxiety and depression scales, as well as sub-categories of “obsessive compulsive” and “paranoid- ideation.” Findings demonstrated the broad effect of microflora on the body and to modulate synaptophysin and PSD-95 protein – both signs of synaptic maturation – in the striatum of the forebrain during the sensitive period of synaptogenesis. If applicable to humans, there may be long- term consequences of developing mood disorders in adulthood if the infant gut flora is compromised. The prenatal period, specifically up to 6 weeks of age, is critical for this type of programming because of the ability of the microflora to modulate its development.1 Probiotic supplementation may potentially be able to reverse the excess HPA-axis responsiveness and the associated anxiety-like behavior. Commensal bacteria not only have the ability to influence the HPA axis, but relationship between the gut microflora and neurological function. Animal Studies One animal study1 showed that germ- free mice (gnotobiotic mice that have not been naturally colonized by microorganisms) exhibited an increased hypothalamic-pituitary-adrenal (HPA)-axis responsiveness to stress during adulthood. The mice had decreased sensitivity to the negative feedback of glucocorticoids, resulting in elevated adrenocorticotropic hormone (ACTH) and corticosterone levels – a stressful state resembling anxiety. Heijtz et al2 further demonstrated that the gut microflora of germ-free mice was able Polina Kapoustina, Phillip Rouchotas, ND, MSc The role of the gut in treating psychiatric conditions is not always considered, but current research on the use of probiotics in depression and related mood disorders has gained traction, both as an adjuvant therapy and a preventative measure. This research gives naturopathic physicians a strong foundation to present to their patients and educate them on how the health of their guts directly impacts the health of their minds and vice versa, encouraging them to be mindful of the mind-body connection. This review evaluates the current evidence and possible mechanisms explaining the S t u d e n t S c h o l a r s h i p – 1 s t P l a c e R e s e a r c h R e v i e w Probiotics and Psychiatry Must be coMpleted in full ad form client phone 14
  • 2. NATUROPATHIC DOCTOR NEWS & REVIEWFebruary 2014 markers such as inflammatory cytokines. Yet, it is important to note that with probiotics there is no risk of addiction or memory impairment, as is the case with psychoactive drugs, making a strong case for including probiotics in the protocol for anxiety and depression. Although plenty of questions remain, the benefit of using probiotics to treat behavior disorders is becoming increasingly more apparent. Naturopathic medicine has a critical role to play in implementing this evidence in clinical practice, as we integrate our understanding of stress-induced disease and the mind-body connection. mind. Hence, probiotic supplementation can have positive behavioral effects, even in a healthy population. Benton et al13 also conducted research on healthy subjects in England, investigating the effect of probiotics specifically on mood and memory. The supplementation influenced mood in subjects with the lowest baseline mood, with no improvement in memory (see Table 1). Rao et al14 were the only investigators examining a population with a specific diagnosis, in this case chronic fatigue syndrome (CFS), in which over 50% of patients present with anxiety. Mental health conditions and “functional somatic disorders” like CFS have higher incidence in developed countries. This may be due to a changing microbial environment in these countries, leading to an elevation of inflammatory cytokines, which at even low levels can produce anxiety and depression in otherwise healthy adults, as mentioned above.13 Rao found that after 8 weeks, there was a significant decrease in anxiety among those taking probiotics (see Table 1). It is interesting to note that there was a consequential rise in probiotic strains in the stool that were not supplemented in the subjects, indicating improvements in overall gut health.14 This body of research suggests that the brain-gut links proposed in animal studies are validated clinically. The action of gut microflora on the HPA axis and CNS messaging may indeed explain the radically positive results on mood, anxiety, and stress in the human studies outlined here. However, it is important to distinguish between direct and indirect consequences of probiotic supplementation in the studies. An example of an indirect effect on the CNS or ENS would be improved bowel movements due to the probiotic, which research has shown leads to improved mood.15 We cannot assume that probiotics directly affect the CNS, although animal studies do suggest possible mechanisms. In all of the studies discussed here, probiotic supplementation produced none of the side effects that would be expected with conventional antidepressants. Further investigation into dosing and probiotic strain is needed. Some of the research used a dairy beverage for delivering the probiotic formulations. It would be interesting to see the effects of higher-dose, pill-form probiotics. Moreover, most studies were done on healthy subjects, rather than patients with mental health diagnoses. Baseline mood was not always measured at the beginning of the study. To properly evaluate the results, it’s important to know if the subjects may have already been happy Benton13 did indeed divide subjects into 3 categories, according to baseline mood in the first 4 days of the study, using POMS scores. Overall, probiotics produce positive results on mood and anxiety in a healthy population, and may indeed be an option for adjuvant or preventative therapy. Conclusion We are on the cusp of a surge in research on probiotic applications in psychiatry. There are still trials to be done on populations with more serious mental health conditions, including identification of the proper flora strain(s) and dose for each condition; nonetheless, we are continually realizing the vital role of the gut on CNS functions. Future studies should evaluate the coadministration of probiotics with psychotropic drugs on a larger sample size, taking into account baseline physiological S t u d e n t S c h o l a r s h i p – 1 s t P l a c e R e s e a r c h R e v i e w Table 1. Effects of Probiotic Supplementation on Depression, Anxiety, Stress, and Mood – Human Trials Reference Method Outcome Tillisch; 201310 RCT; 36 healthy women, ages 18–55 years 125 g BID, 4 weeks Probiotic yogurt with Bifidobacterium lactis, Lactobacillus bulgaricus, Streptococcus thermophilus, and Lactococcus lactis OR non-fermented dairy OR no beverage Assessed with blood flow assessments (fMRI) while performing emotional tasks Probiotic group showed lower brain reactivity to an emotional task (p=0.004), compared to non-fermented dairy group and no beverage group. The probiotics group showed decreased connectivity of an amygdala-centered network with the insula, dorsal striatum, and lateral prefrontal cortex. Messaoudi; 201111 RCT; 25 subjects with urinary free cortisol levels <50 ng/mL at baseline (article addendum to study below), aka less-stressed subjects Lactobacillus helveticus and Bifidobacterium longum (3 x109 cfu) OR Placebo Subjects assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale (PSS), and 24-hour urinary free cortisol Anxiety and depression scores significantly improved, as in the general population. Three other sub-scores also improved: “obsessive compulsive,” “anxiety,” and “paranoid-ideation.” No side effects. Good safety profile. Messaoudi; 201112 RCT; 66 healthy subjects Once daily, 30 days Lactobacillus helveticus and Bifidobacterium longum (1.5 g; 3 x109 cfu) OR Placebo Subjects assessed with the HSCL-90, the HADS, the PSS, the Coping Checklist (CCL), and 24-hour urinary free cortisol Overall decrease in the scales measuring anxiety and depression, due to decrease in somatization and anger- hostility. Improvement in mood: significantly reduced psychological distress in volunteers (p<0.05). No group differences were observed in the PSS. Urinary free cortisol levels were significantly reduced by the probiotics (p<0.05). Benton; 200713 RCT; 124 physically healthy subjects, mean age of 62 years Once daily, 3 weeks Milk drink with Lactobacillus casei Shirota (6.5 x 109 cfu) OR Placebo Mood (questionnaire-based POMS) and cognition (Wechsler Memory Scale) measured at baseline and after 10 and 20 days of supplementation  Mood: Probiotics failed to influence mood in 5/6 POMS mood dimensions, but significance in the bottom third with the lowest baseline mood. Memory: Placebo group demonstrated better recall compared to probiotic group.   Rao; 200914 Pilot RCT; 39 patients with chronic fatigue syndrome (CFS) Once daily, 8 weeks Lactobacillus casei Shirota (24 billion cfu) OR Placebo Patients provided stool samples and were assessed with the Beck Depression and Beck Anxiety Inventories before and after the intervention. A significant decrease in anxiety among those taking the active LcS compared to the placebo (p = 0.01); no statistically significant changes in depression. A 73.7% increase in Bifidobacteria and Lactobacillus in treated group (vs 37.5% Bifidobacteria and 43.8% Lactobacillus in placebo group) (RCT – Randomized, controlled trial; fMRI – functional magnetic resonance imaging; POMS – Profile of Mood States) References1. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic-pitutary- adrenal system for stress response in mice. J Physiol. 2004;558(Pt 1):263-275. 2. Diaz Heijtz R, Wang S, Anuar F, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA. 2011;108(7):3047-3052. 3. Desbonnet L, Garrett L, Clarke G, et al. The probiotic Bifidobacteria infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43(2):164-174. 4. Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011;23(3): 255-264. 5. Goehler LE, Park SM, Opitz N, et al. Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain Behav Immun. 2008;22(3):354-366. 6. Graff LA, Walker JR, Bernstein CN. Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management. Inflamm Bowel Dis. 2009;15(7):1105-1118. 7. Logan A, Katzman M. Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses. 2005;64(3):533-538. 8. O’Mahony SM, Marchesi JR, Scully P, et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009;65(3):263–267. 9. Goodhand JR, Greig FI, Koodun Y, et al. Do antidepressants influence the disease course in inflammatory bowel disease? A retrospective case- matched observational study. Inflamm Bowel Dis. 2012;18(7):1232-1239. 10. Tillisch K, Labus J, Kilpatrick L, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013;144(7):1394-1401. 11. Messaoudi M, Lalonde R, Violle N, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr. 2011;105(5):755-764. 12. Messaoudi M, Violle N, Bisson JF, et al. Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes. 2011;2(4):256-261. 13. Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur J Clin Nutr. 2007;61(3):355-361. 14. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009;1(1):6. 15. Logan A, Katzman M. Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses. 2005;64(3):533-538. MUST BE COMPLETED IN FULL AD FORM CLIENT PHONE *These statements have not been evaluated by the Food and Drug Administration.The contents are not intended to diagnose, treat, cure or prevent any disease. ANTI-INFLAMMATORY™ FORMULA Learn more about Anti-Inflammatory™ formula, and view the full ingredients list at To order, call toll free (877) 686-7325 Anti-Inflammatory™ provides relief in both acute and chronic inflammatory conditions.* Formula includes: Bromelain to block certain pro-inflammatory metabolites that accelerate the inflammation process. Curcumin (Meriva®) to maintain a healthy inflammatory response with antioxidant and immunostimulatory effects. Serrapeptase and Protease to reduce inflammation by neutralizing the biochemicals of inflammation to levels where repair of injured tissue can take place. Polina Kapoustina is a 3rd- year student at the Canadian College for Naturopathic Medicine (CCNM). She is the founder of the CCNM Pediatrics Club ( and served as the VP Communications 2012-2013 in the National Medical Student Association (NMSA). She is also the Eastern Current representative at CCNM. Polina loves the outdoors and adventure sports. She is passionate about naturopathic medicine and can’t wait to start helping people get well! Philip Rouchotas MSc, ND
 has been a practicing naturopathic doctor since 2004. His areas of clinical focus include metabolic disorders (diabetes, high blood pressure, elevated cholesterol, overweight/obesity), autoimmune conditions (arthritis, IBD, chronic migraine, asthma, eczema, psoriasis, lupus), and psychiatric con- cerns (depression, bipolar, anxiety, ADHD, insomnia, schizophrenia). Philip serves as an associate professor at the Canadian College of Naturopathic Medicine, respon- sible for assimilation and delivery of the second-year cur- riculum in clinical nutrition. He is also the editor-in--chief of Integrated Healthcare Practitioners, a peer-reviewed journal reaching naturopathic doctors, chiropractors, and medical doctors across Canada. Philip graduated from CCNM in 2004, preceded by an honours undergraduate degree in nutritional sciences and a masters degree in nutritional sciences, both from the University of Guelph. 16

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