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. 2020 Mar 9;11(4):890–907. doi: 10.1093/advances/nmaa016

TABLE 1.

Examples of published literature evidence (from in vitro, animal, and human studies) of components within dietary patterns related to depression in humans or emotional behaviors in animals, which directly affect the host but also interact with the gut microbiota1

Dietary component Effect Summary Subject Ref.
Phytochemicals
 Cocoa polyphenols Affected mood In an RCT in adults, 500 mg supplement for 30 d increased self-rated calmness and contentedness compared with placebo. Human Pase et al. (183)
Altered microbial growth A 6-wk diet with 10% cocoa in rats caused a decrease in Bacteroides, Clostridium, and Staphylococcus genera in feces. Animal Massot-Cladera et al. (184)
In vitro digestion with 1 g cocoa powder/60 mL water. 38.6% of phenols were solubilized, and an increase in Bifidobacteria, Lactobacilli, and butyrate was found. In vitro Fogliano et al. (185)
Altered immune function A 6-wk diet with 10% cocoa in rats caused an altered toll-like receptor pattern and increased gastrointestinal immunoglobin A secretion. Animal Massot-Cladera et al. (184)
 Blueberry extract (anthocyanins) Affected mood and cognition In a BCT, in children and young adults, a single drink containing 253 mg anthocyanins increased positive but did not change negative affect scores using the “Positive and Negative Affect Scale” compared with a placebo drink. Human Khalid et al. (186)
A 5% blueberry drink given to rats for 8 wk protected against cognitive impairment during chronic mild stress. Animal Guo et al. (187)
Altered host metabolites Decreased plasma norepinephrine and dopamine concentrations, and brain concentrations of antioxidant compounds due to 8 wk of chronic mild stress were attenuated by a 5% blueberry drink. Animal Guo et al. (187)
Fiber (prebiotic)
 GOS, PDX, and FOS Attenuated stress-induced behaviors and mood, and gene expression in the brain Male rats were fed diets containing GOS + PDX for 4 wk and then underwent inescapable stressors. The prebiotic reduced stress-induced exaggerated freezing and deficit in escape latency, and attenuated c-fos mRNA in parts of the brain. Animal Mika et al. (188)
Male and female rats underwent early-life stress (maternal separation model). Prebiotic supplementation of GOS + FOS for 5 wk after the stress attenuated stress-induced deficits in spatial memory and locomotion, but not anxiety-like behaviors. Animal McVey Neufeld et al. (189)
RCT, patients with depression: 8 wk supplementation with 5 g GOS resulted in decreases in scores on the Beck Depression Inventory compared with placebo. Human Kazemi et al. (190)
Healthy volunteers given either FOS or GOS daily for 3 wk. Salivary cortisol awakening response and emotional bias (attention to negative information) were decreased after GOS but not FOS. Human Schmidt et al. (191)
Altered the gut microbiota Prebiotic diet of GOS + FOS increased Lactobacillus rhamnosus and also Lactobacillus spp. Animal Mika et al. (188)
44 elderly subjects, given 5.5 g/d GOS or placebo for 10 wk in a double-blind, placebo-controlled, crossover study. Increase in Bifidobacterium spp., Lactobacillus Enterococcus spp., Clostridium coccoides–Eubacterium rectale, and a decrease in Bacteroides spp., Clostridium histolyticum group, Escherichia coli, and Desulfovibrio spp. Human Vulevic et al. (192)
Altered immune function Increases in immune function, including reduced proinflammatory cytokines and increased anti-inflammatory cytokines, phagocytosis, and NK cell activity. Human Vulevic et al. (192)
 Wheat arabinoxylan May counteract effects of high-protein diet on the gut microbiota In pigs fed a 4-wk Western-type diet, added soluble fiber (wheat arabinoxylan) increased carbohydrate fermentation and reduced protein fermentation and fermentation products such as ammonia. Animal Williams et al. (193)
Vitamins/minerals
 Vitamin D Regulated gut physiological processes Vitamin D receptors in the gut regulate processes including epithelial barrier function and immune processes. Review Barbáchano et al. (194)
Associated with changes in the gut microbiota Plasma 25-hydroxyvitamin D and vitamin D supplementation in women in their 36th week of pregnancy were measured, and compared with fecal samples in their 1-mo-old infants. Increased concentrations of both were associated with decreased Bifidobacteriumspp. and Clostridium difficile and increased B. fragilis. Human Talsness et al. (182)
 Magnesium Dietary deficiency altered behavior 30 mice fed a magnesium-restricted diet for 6 wk had increased immobility in the forced swim test and increased hippocampal IL-6 compared with mice fed a normal diet. Animal Winther et al. (179)
Associated with changes in the gut microbiota The cecal gut microbiota was also altered, with cluster analysis showing significant differences between the diets.
 Vitamin A Associated with changes in the gut microbiota and the gut mucosal barrier A vitamin A–deficient diet in rats increased total bacteria, decreased Lactobacillus spp., and increased Escherichia coli. Mucin-producing goblet cells were altered and expression of toll-like receptors was increased. Animal Amit-Romach et al. (195)
Vitamin A deficiency in children aged 1–12 mo with persistent diarrhea showed significantly different gut microbiota than in those with normal serum vitamin A concentrations. Human Lv et al. (196)
Macronutrients
 ω-3 fatty acids Immunomodulatory The metabolic and inflammatory effects in wild-type mice fed a diet with a high ratio of ω-6 to ω-3 were able to be prevented with antibiotic treatment, or by cohousing mice with Fat-1 transgenic mice, which endogenously produce ω-3 fatty acids. Animal Kaliannan et al. (176)
Increased endogenous antimicrobial defenses Fat-1 mice were found to produce increased intestinal alkaline phosphatase, an endogenous antimicrobial compound, which reduced gut permeability and LPS production. Animal Kaliannan et al. (176)
Restored gut dysbiosis Fat-1 transgenic mice were found to be protected against gut dysbiosis and obesity caused by a Western-style diet after early-life antibiotic exposure. Animal Kaliannan et al. (197)
Supplementation of 100–250 mg/d ω-3 FA (80% EPA, 20% DHA) for 12 wk to female rats reversed stress-induced gut dysbiosis. Animal Pusceddu et al. (177)
Increased gut microbial metabolites (SCFAs) An 8-wk open label trial using an EPA/DHA supplement drink or capsule in adult males and females reversibly increased SCFA-producing bacteria including Bifidobacterium,Roseburia, and Lactobacillus. Human Watson et al. (198)
Deficiency affected mood as well as the gut microbiota An ω-3 FA–deficient diet in pregnant mice and their male offspring resulted in an elevated ratio of Firmicutes to Bacteroidetes in the offspring, along with altered behavior and immune function. Animal Robertson et al. (178)
Increased depressive behavior (immobility in forced swim test), decreased sociability (three chamber test), isolation-induced ultrasonic vocalizations in adulthood, and decreased memory (novel object recognition test) in both adolescence and adulthood. Increased contextual fear conditioning.
 High fat, particularly saturated fat Altered microbiota composition A high-fat diet in mice decreased Ruminococcaceae and increased Rikenellaceae compared with a carbohydrate diet. Animal Daniel et al. (199)
Increase in Firmicutes, particularly the family Erysipelotrichaceae, and decrease in Bacteroidetes in mice fed a high-fat diet. Animal Fleissner et al. (200)
Mice fed a low-fat diet who switched to a high-fat diet had a significant shift in microbiome composition within 1 d. Increased Firmicutes, particularly the Erysipelotrichi class, Bacilli, and decreased Bacteroidetes. Animal Turnbaugh et al. (201)
BALB/c mice fed a high-fat diet showed alterations in the gut microbiota including an increase in Firmicutes, particularly in the families Rumunococcaceae and Lachnospiraceae, a decrease in the Bacteroidetes phylum, and a resulting decrease in the ratio of Bacteroidetes to Firmicutes. Animal Pyndt Jørgensen et al. (202)
Altered anxiety-like behavior Mice fed a high-fat diet displayed less burrowing (anxiety-like) behavior, and displayed reduced memory in the Morris water maze test compared with mice fed a control diet. The diets were not isocaloric, and the high-fat diet mice also gained more weight. Animal Pyndt Jørgensen et al. (202)
 High-fat, high-sugar diet Altered microbiota composition A Western-style diet in humanized mice resulted in increased Erysipelotrichi class (mainly Clostridium innocuum, Eubacterium dolichum, and Catenibacterium mitsuokai genera) and Bacilli class (mainly Enterococcus spp. genera). The microbial shift occurred after only a single day. Animal Turnbaugh et al. (201)
 High-sugar diet Positive change in behavior when the gut microbiota was not altered A high-sucrose diet did not alter the gut microbiota in BALB/c mice compared with a control diet and did alter some behaviors, but in a positive direction (increased latency to immobility in the forced swim test, less goal-orientated burrowing, and less anxiety-like behavior in the triple test). Animal Pyndt Jørgensen et al. (202)
 Red meat Modified gut microbiota composition A comparison between a diet rich in red meat or whole grains (10-wk crossover trial) showed that increased red meat consumption increased the genera Clostridium spp. from the phylum Firmicutes. Human Foerster et al. (203)
Microbial metabolism of heme-rich meat increases oxidative compounds Comparison of meat types varying in heme content (beef, pork, chicken) in an in vitro digestion model showed that heme-rich meat caused higher concentrations of the nitrosoxide compound–derived DNA adduct O6-carboxymethylguanine. In vitro Vanden Bussche et al. (204)
Food additives
 Emulsifiers CMC and P80 Altered gut microbiota composition C57Bl/6J mice were given either CMC or P80 emulsifiers at 1% in their drinking water from weaning until 3 mo old. The gut microbiota was altered by the treatment. Interestingly the outcomes differed between males and females. In males, Firmicutes phylum and Oscillospria, Coprococcus, and rc4_4 genera were reduced, as well as reduced Dorea with P80, and reduced Bacteroides, Burkholderia, Clostridium, and Veillonella with CMC. In females, Bacteroides, Sphingomonadales, Sphingomonas, and Ruminococcus were reduced, and there was an increase in Anaeroplasma with P80, and the Proteobacteria phylum and Clostridium and Burkholderia genera with CMC. Animal Holder et al. (205)
Altered anxiety-like behavior Treatment with emulsifiers decreased sociability in the 3-chamber test in females only, and increased locomotion in the Elevated Plus Maze in males only. No difference found in forced swim test or light-dark box.

1BCT, blinded crossover trial; CMC, carboxylmethylcellulose; FOS, fructooligosaccharide; GABA, γ-aminobutyric acid; GOS, galactooligosaccharide; PDX, polydextrose; P80, polysorbate 80; RCT, randomized controlled trial.