Rob Fancher, NDTR, FSP, Dietetic Intern • Sodexo New Bedford Campus

September 4, 2018
 Learning objectives
 Ice breaker
 Background Information
 Rationale for research
 Overview of current research
 Probiotic consumption effects
 Conclusions
 Applications for practice
 Future research
 Questions
Objective 1
Participants will be able to
explain the evidence-based
associations between probiotics
and their effects on markers of
neuropsychiatric disorders
Objective 2
Participants will be able to make
evidence-based recommendations
to patients/clients in regards to
probiotic food consumption and/or
supplementation and its relationship
to mental health
How do you yogurt?

Other fermented foods?

Microbiome – what is it?
“The ecological community of commensal, symbiotic, and pathogenic organisms that
literally share our space” – Joshua Lederberg, Molecular Biologist

Roles:
Nutrient metabolism
• Fermentation of CHO -> SCFA
• Suppress inhibition of lipoprotein lipase
• Microbial proteinases & peptidases
• Synthesis of vitamin K & most B vitamins
• Breakdown of polyphenols -> portal vein
Xenobiotic & Drug metabolism
Antimicrobial protection & Immunomodulation
Integrity of gut barrier
Microbiome – what is it? (continued…)

Factors that influence microbiota composition:

Age
Diet
Antibiotics
Prebiotics, Probiotics, “Synbiotics”

Contraindications to supplemental probiotics:

Immunocompromised/Critically ill – Chemo/XRT, HIV/AIDS
Neonates*
Saccharomyces - Central venous catheters
Gut-Brain Axis – what is it?
Link between central and enteric nervous systems
Neural, Endocrine, Immune, Humoral signals
Neuropsychiatric Disorders <-> Gut-Brain Axis
Hypothalamic-Pituitary-Adrenal Axis
Response to stressors
Tryptophan -> Serotonin
GABA – gamma aminobutyric acid
Intestinal permeability
epithelial barrier
“leaky gut syndrome” – unrecognized
IBS, IBD
Fermented foods Probiotics help the gut What else are they good for?

• Thousands of years • Constipation • Mood

• Rising in popularity • Diarrhea • Depression
• Variety of options • IBD • Anxiety
• Colon Cancer • Severe illness
• H. pylori
Do supplements work?
Study Study Design Sample Size/ Population Characteristics Mental Health Results
Study Duration Parameters
-General health
-Iran questionnaire (GHQ)
Randomized, double-blind, n= 70 ++GHQ, DASS
Mohammadi et al. (2016) -Generally healthy -Depression anxiety and
placebo-controlled 6 weeks --HPA axis
petrochemical workers stress scale (DASS)
-HPA axis (secondary)
-Leiden Index of Depression
-Netherlands Sensitivity (LEIDS-r)
Steenbergen et al. Randomized, triple-blind, n= 40 ++LEIDS-r
-Generally healthy -Beck Depression Inventory II
(2015) placebo-controlled 4 weeks --BDI-II, BAI
-No psych/neuro disorders (BDI-II)
-Beck Anxiety Inventory (BAI)
Ongoing, randomized,
n= 75 -Behavior patterns
Pärtty et al. double-blind, placebo- -Finland ++ADHD, AS, Neural
6 months with 13 year -Psych eval w/ dxs
(2015) controlled, prospective -Infants pathways
follow-up -Fecal analysis
cohort
-Beck Depression Inventory ++BDI, Insulin,
Randomized, double-blind, n= 40 -Iran
Akkasheh et al. (2016) (BDI) Antioxidants
placebo-controlled 8 weeks -Major depressive disorder
-Metabolic status --FPG, Lipids
-U.S.A., Maryland -Positive and Negative
Randomized, double-blind, n= 58 ++GI Fxn
Dickerson et al. (2014) -Schizophrenia, moderately Syndrome Scale (PANSS)
placebo-controlled 14 weeks --PANSS score
severe psychotic symptoms -GI Fxn (secondary)
• Randomized, DB, PC trial - Generally healthy petrochemical workers
• Yogurt and Capsule groups, 6 weeks
• 100g/d probiotic yogurt + placebo capsule
• 100g/d conventional yogurt + probiotic capsule
• 100g/d conventional yogurt + placebo capsule

• Usual intake and physical activity, no additional probiotics/synbiotics

• Significant improvement of GHQ in both probiotic groups (p = 0.007, 0.001; yogurt, capsule)
• Significant improvement of DASS in both probiotic groups (p = 0.02, 0.006)
• No effect on HPA axis
• Randomized, TB, PC trial – Generally Healthy Adults
• No neuro/psych disorders

• Cognitive reactivity to sad mood

• 2g Freeze-dried probiotic powder, dissolved in water or
lukewarm milk, 4 weeks
• Significant reduction in reactivity to depression,
aggressive and ruminative thoughts
• Mostly female groups
• No control for consumption of other
probiotics/fermented foods
• No stool confirmation
• Randomized, DB, PC prospective cohort – Secondary study
• Neuropsychiatric disorders later in childhood
• ADHD, Asperger's Syndrome
• 4 week pre-birth supplementation, 6 months post-birth -> mother ->
breastmilk OR directly to child if formula-fed
• Fecal samples 3 wk, 3, 6, 12, 18, 24 mos, 13 yrs
• ADHD or AS in 6/35 placebo group, none in probiotic group at 13 yrs (p =
0.008)
• Log cells/g lower in those with ADHD/AS up to 24 months
• No significant difference in fecal samples at 13 yrs
• Randomized, DB, PC trial
• Major depressive disorder (MDD)
• Probiotic capsules, 8 weeks
• Usual intake and physical activity, no additional supplements or medications
• Significantly decreased BDI total score in probiotic group (p = 0.001)
• Significant decreases in Serum Insulin, HOMA-IR, and hs-CRP concentrations (p = 0.03)
• Significant increase in GSH (p = 0.02)
• No sig. change in FPG, HOMA-B, Lipid profiles, TAC
• Randomized, DB, PC trial
• Schizophrenia or Schizoaffective disorder
• Outpatient tx
• Moderately severe psychotic symptoms

• Probiotic tablet, 14 weeks

• Psych symptom eval every 2 wks, GI fxn weekly
• No significant effect on PANSS score
• Less likely to report severe difficulty moving bowels (p = 0.003)
Study Study Design Sample Size/ Population Characteristics Mental Health Results
Study Duration Parameters
-General health
-Iran questionnaire (GHQ)
Randomized, double-blind, n= 70 ++GHQ, DASS
Mohammadi et al. (2016) -Generally healthy -Depression anxiety and
placebo-controlled 6 weeks --HPA axis
petrochemical workers stress scale (DASS)
-HPA axis (secondary)
-Leiden Index of Depression
-Netherlands Sensitivity (LEIDS-r)
Steenbergen et al. Randomized, triple-blind, n= 40 ++LEIDS-r
-Generally healthy -Beck Depression Inventory II
(2015) placebo-controlled 4 weeks --BDI-II, BAI
-No psych/neuro disorders (BDI-II)
-Beck Anxiety Inventory (BAI)
Ongoing, randomized,
n= 75 -Behavior patterns
Pärtty et al. double-blind, placebo- -Finland ++ADHD, AS, Neural
6 months with 13 year -Psych eval w/ dxs
(2015) controlled, prospective -Infants pathways
follow-up -Fecal analysis
cohort
-Beck Depression Inventory ++BDI, Insulin,
Randomized, double-blind, n= 40 -Iran
Akkasheh et al. (2016) (BDI) Antioxidants
placebo-controlled 8 weeks -Major depressive disorder
-Metabolic status --FPG, Lipids
-U.S.A., Maryland -Positive and Negative
Randomized, double-blind, n= 58 ++GI Fxn
Dickerson et al. (2014) -Schizophrenia, moderately Syndrome Scale (PANSS)
placebo-controlled 14 weeks --PANSS score
severe psychotic symptoms -GI Fxn (secondary)
• 4/5 studies show statistically significant benefits on symptoms of various
neuropsychiatric disorders
• Both food and supplemental forms
• Adjuvant therapy
• May not be effective for more severe illness
• Limiting factors/variables
• More research required
 Mild-Moderate Early Intervention in Severe Illness
Depression, Anxiety Children
May not help
May help improve or May help prevent improve symptoms
prevent symptoms ADHD, AS
• Generally safe to recommend either food-based or
supplemental probiotics
• Yogurt – individualized response in those with lactose
intolerance
• Dose/genus/species combination
1-10 billion CFUs

uBiome SmartGut™
Prescribed, Insurance – OON coverage ™
uBiome Explorer™
$89, $199, $399
• Other foods such as kimchi, sauerkraut in relation to mental health
• Larger sample sizes, longer duration
• Control for antibiotic use
• Combinations of strains
• synergy vs competition
Thank you!!
• Jandhyala, S. M., Talukdar, R., Subramanyam, C., Vuyyuru, H., Sasikala, M., & Reddy, D. N. (2015, August 07). Role of the normal gut
microbiota. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528021/
• Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015, April-June). The gut-brain axis: Interactions between enteric microbiota,
central and enteric nervous systems. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/
• Regulatory Oversight and Safety of Probiotic Use - Volume 16, Number 11-November 2010 - Emerging Infectious Diseases journal - CDC.
(2011, March 08). Retrieved from https://wwwnc.cdc.gov/eid/article/16/11/10-0574_article
• Mohammadi, A. A., Jazayeri, S., Khosravi-Darani, K., Solati, Z., Mohammadpour, N., Asemi, Z., . . . Eghtesadi, S. (2015). The effects of
probiotics on mental health and hypothalamic–pituitary–adrenal axis: A randomized, double-blind, placebo-controlled trial in
petrochemical workers. Nutritional Neuroscience, 19(9), 387-395. doi:10.1179/1476830515y.0000000023
• Steenbergen, L., Sellaro, R., Hemert, S. V., Bosch, J. A., & Colzato, L. S. (2015). A randomized controlled trial to test the effect of
multispecies probiotics on cognitive reactivity to sad mood. Brain, Behavior, and Immunity, 48, 258-264. doi:10.1016/j.bbi.2015.04.003
• Pärtty, A., Kalliomäki, M., Wacklin, P., Salminen, S., & Isolauri, E. (2015). A possible link between early probiotic intervention and the risk of
neuropsychiatric disorders later in childhood: A randomized trial. Pediatric Research, 77(6), 823-828. doi:10.1038/pr.2015.51
• Akkasheh, G., Kashani-Poor, Z., Tajabadi-Ebrahimi, M., Jafari, P., Akbari, H., Taghizadeh, M., . . . Esmaillzadeh, A. (2016). Clinical and
metabolic response to probiotic administration in patients with major depressive disorder: A randomized, double-blind, placebo-controlled
trial. Nutrition,32(3), 315-320. doi:10.1016/j.nut.2015.09.003
• Dickerson, F. B., Stallings, C., Origoni, A., Katsafanas, E., Savage, C. L. G., Schweinfurth, L. A. B., … Yolken, R. H. (2014). Effect of Probiotic
Supplementation on Schizophrenia Symptoms and Association With Gastrointestinal Functioning: A Randomized, Placebo-Controlled
Trial. The Primary Care Companion for CNS Disorders, 16(1), doi:10.4088/PCC.13m01579