A prebiotic fiber alters the gut microbiome and improves mental health Original paper

In this randomized controlled trial, supplementation with the dietary fiber oligofructose increased levels of the gut bacteria Bifidobacterium and improved measures of depression, anxiety, and mood in adults with mild-to-moderate anxiety and stress.

The effect of two inulin-type fructans (ITFs), oligofructose (also called fructooligosaccharide) and 2’-fucosyllactose, on the gut microbiome and mood.

The primary outcome was Bifidobacterium microbiome counts. The secondary outcomes included microbial load and composition, depression symptomatology, anxiety symptomatology, mood, sleep quality, salivary cortisol, urinary metabolites, gastrointestinal sensations, and bowel habits.

92 adults (average age of 28; average BMI of 23.5 ; 67% women, 33% men) with mild-to-moderate anxiety and stress.

Stress was determined using the Patient Health Questionnaire-9 (PHQ-9) and anxiety status was determined using the State Trait Anxiety Inventory (STAI).

The researchers conducted a 5-week randomized controlled trial (RCT) involving 4 groups. Participants were randomized to take the following:

• Maltodextrin (10 grams/day), placebo group
• Oligofructose (8 grams/dday) plus maltodextrin (2 grams/day)
• 2’-fucosyllactose (2 grams/day) plus maltodextrin (8 grams/dday)
• Oligofructose (8 grams/dday) plus 2’-fucosyllactose (2 grams/day)

Stool samples were collected and analyzed for gut microbial load and composition. Mental health was assessed with various questionnaires: Beck Depression Inventory (BDI); for depression), STAI (for anxiety) versions Y1 and Y2, and Positive and Negative Affect Schedule (PANAS-SF, for aspects of mood). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Urine and saliva were collected to assess changes in urinary metabolites and cortisol awakening response. Bowel habits and gastrointestinal sensations were monitored with daily diary and Bristol Stool Form Scale completion for the last week of the intervention and the week before the intervention.

Dietary intake was monitored with 3-day food diaries administered at the beginning and end of the intervention.

All interventions increased Bifidobacterium counts as compared to placebo, and both interventions with oligofructose increased counts more than the intervention with 2’-fucosyllactose only. Only oligofructose alone increased Bacteroides compared to placebo.

Oligofructose, alone or in combination with 2’-fucosyllactose, reduced symptoms of depression and anxiety compared to placebo. All interventions improved mood state and decreased the cortisol awakening response when compared to placebo. Inverse correlations were reported between Bifidobacterium abundance and measures of depression, anxiety, negative affect, and cortisol awakening response.

Both interventions that included oligofructose increased stool consistency compared to 2’-fucosyllactose only, whereas the combination intervention increased stool frequency more than all other groups. There were no differences in gastrointestinal sensations, sleep quality, or urinary metabolites. Daily average fiber intake, excluding the fiber provided by the interventions, was 20 grams per day.

A higher intake of dietary fiber is associated with lower risk of some mental health disorders, such as depression.^[2][3][4] Dietary fibers are essentially carbohydrates that cannot be digested or absorbed by humans but can go on to be fermented by gut microbiota to varying degrees.^[5] If a type of fiber causes specific changes in gut microbial composition and/or activity, thereby improving the health of the host, they can be classified as prebiotics.^[6] Mental health disorders have been associated with an imbalanced gut microbial profile (i.e., dysbiosis), characterized by a decrease in beneficial bacteria and an increase in pathogenic and opportunistic bacteria. This is why prebiotics, as well as probiotics, have been suggested to benefit mental health via the gut-brain axis.^[7][8] Indeed, irritable bowel syndrome (IBS) has consistently been associated with mental health disorders. Substances that influence gut-brain signaling, including prebiotics, probiotics, synbiotics, and fermented foods, have been suggested as key intervention components for improved depression management, along with other dietary, medical, and psychological interventions.^[9]

Inulin-type fructans (ITFs) are some of the few dietary fibers that are accepted by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as prebiotics for their bifidogenic effect (i.e., ability to stimulate bifidobacteria) and beneficial effects on health.^[10] Inulin and ITFs, such as oligofructose, are naturally occurring polysaccharides found in foods such as wheat, onion, and asparagus that belong to a class of dietary fibers known as fructans (i.e., polymers of fructose).^[11] ITFs have consistently shown to promote Bifidobacterium, showing 2–fold to 4-fold increased abundance in 33 of 35 analyzed studies. In addition, ITFs have been shown to promote other beneficial bacteria (albeit less consistently), such as Lactobacillus and Faecalibacterium prausnitzii. Additionally, ITFs have been linked to a range of health benefits, including improvements in intestinal barrier function, insulin sensitivity, lipid profile, calcium and magnesium absorption, and satiety signaling.^[11][10] One noncontrolled study even reported that an increased intake of ITF-rich vegetables (15 grams/day) coincided with a decreased desire to eat sweet, salty, or fatty foods.^[12] However, any benefits may depend on the specific ITF because different chain lengths may have different effects, and the individual characteristics of the people eating them, like age.

Bifidobacterium is an inactive, spore-producing and gas-producing gram-positive bacterium that is consistently associated with mental health benefits and seems to increase with higher fiber intakes.^[7][8] These bacteria are known to ferment dietary fiber and are often the first microbiota to colonize the intestines of newborns, playing a key role in physiological development, including immune system maturation.^[13] Combinations of Bifidobacterium and Lactobacillus tend to be supplemented for depression management^[14] based on the fact that people with depression tend to have lower Bifidobacterium and Lactobacillus levels compared to controls without depression.^[15][16] Not only have several Bifidobacterium species demonstrated mental health benefits when given as supplements,^[8] but increases in Bifidobacterium are a commonly reported microbial change following the type of prebiotic interventions^[17] that have been linked to mental health benefits.^[7] Oligosaccharides appear to be preferentially metabolized by bifidobacteria because they have the enzymes necessary to break the specific linkages holding together the polysaccharides.^[18] Certain strains have also evolved specific metabolic capabilities to degrade human milk oligosaccharides (such as 2’-fucosyllactose) that are particularly important for the development of newborn intestinal microbiota and metabolic and immune systems.^[10] Interestingly, oligofructose is a subgroup of inulin that is often used to fortify foods with fiber and contribute a pleasant sweetness, flavor, and mouthfeel, especially for fat-reduced foods.^[11] It seems that oligofructose may be a food component that can enhance not only the taste but also the health effects of food.

Potential mechanisms behind the mental health benefits of Bifidobacterium

Adapted from Li et al. (2023) and Yang et al. (2023).

Although the associations between levels of certain bacterial genus and mental health benefits could be attributed to other factors or a combination of factors, there are several putative mechanisms by which prebiotics and probiotics may improve mental health. Bifidobacteria has been suggested to inhibit inflammatory signaling, reduce pathogenic bacteria and lipopolysaccharides, increase short-chain fatty acids, modulate neurotransmitter synthesis by stimulating the vagus nerve as well as producing neuroactive metabolites, and regulate the hypothalamus-pituitary-adrenal axis (HPA axis), a biological system that coordinates stress response.^[8][7][19] The link between inflammation and mood disorders via the gut-brain axis has been suggested as a new target for treatment strategies following animal studies,^[20][21] but mechanistic studies can be more difficult to conduct given the nature of the target outcomes involved in the gut-brain axis. Not many human studies have directly evaluated alterations in metabolic function or metabolite production (e.g., short-chain fatty acids) associated with ITF-induced changes in gut microbial composition.^[11] This may be because the limitations of these methods are still being worked out, such as where and when to sample (fermentation metabolites are mostly produced and used within the intestine, so stool samples are likely a poor measure) and method standardization and data integration.^[22] However, study quality is improving along with our understanding of the field, and the relevant variables involved are slowly becoming clearer.

A greater baseline fiber intake and lower baseline abundance of Bifidobacterium have been associated with a greater bifidogenic effect of ITF intervention.^{[23][24][25][26]} A higher habitual dietary fiber intake (39 gram/day) has been associated with a greater gut microbial response, especially an increase in Bifidobacterium, to an ITF intervention (50:50 inulin to fructo-oligosaccharide mix), when compared to low habitual dietary fiber intake (18 grams/day).^[26] In other words, a lower habitual fiber intake appears to favor a more stable gut microbial community that is more resistant to change. Despite the uncertainty of specific interactions and mechanisms within the gut-brain axis regarding fiber and mental health, the overall trend suggests that greater fiber intake (preferably from whole foods) improves mental health,^{[2][4][8][7][11]} but it should be combined with other psychological and medical intervention for optimal treatment.^[9]

At the phylum level, both interventions that included oligofructose increased Actinobacteria, whereas the only oligofructose intervention increased Bacteroides and Firmicutes, compared to placebo.

A 2021 meta-analysis of 33 randomized controlled trials reported improvements in blood glucose, serum insulin, and blood lipids after ITF interventions, with greater benefits in people with prediabetes and diabetes. Read the Examine Study Summary here.^[1]