Dietary intervention restores gut microbiome and offers protection against chronic diseases

Study finds that a non-industrialized diet improves gut health, reduces disease risk, and enhances microbiome interactions linked to cardiometabolic benefits.

Food products representing the MIND diet created to reduce dementia and the decline in brain health.Study: Cardiometabolic benefits of a non-industrialized-type diet are linked to gut microbiome modulation. Image Credit: monticello/Shutterstock.com

In a recent study published in Cell, researchers investigated the effects of a microbiome restoration strategy in healthy adults.

Background

Humans have complex microbiomes in the gastrointestinal (GI) tract that contribute to host development, health, and fitness. This symbiosis has evolved in conditions distinct from modern industrialized societies over millions of years.

Lifestyle factors hallmarks of industrialization cause nutrient undersupply to the gut microbiota and constitute hurdles to symbiont transmission.

While these factors have substantially contributed to a higher life expectancy through food security and infectious disease prevention, they are linked to a higher risk of noncommunicable diseases (NCDs). This has led to hypotheses that the increase in NCDs might be due to disruptions in host-microbiome symbiosis.

Industrialization has led to a decrease in gut microbiome diversity and fiber fermentation, an increase in pro-inflammatory microbes, and a loss of immunomodulatory and fiber-degrading microbes.

Studies in mice have demonstrated that Western diets resulted in the starvation and extinction of commensal microbes. As such, there is a strong rationale to restore gut microbiota and redress the effects of industrialization.

The study and findings

In the present study, researchers investigated the effects of a microbiome restoration strategy in healthy Canadians.

The strategy comprised a bacterium rarely present in industrialized microbiomes, i.e., Limosilactobacillus reuteri, and a non-industrialized microbiome restore diet. Two bacterial strains were isolated from Germany (DSM 20016T) and rural Papua New Guinea (PB-W1).

The restore diet was designed based on foods consumed in Papua New Guinea that were available in Canada, such as rice, cabbage, cucumber, etc., and foods rich in stachyose and raffinose.

A randomized controlled feeding trial was conducted in healthy adults to evaluate the effects of the microbiome restoration strategy. Subjects were randomized to consume the restore diet or their usual diet for three weeks.

After a washout period of three weeks, participants were crossed over to the other diet for another three weeks, followed by an additional three-week washout period. Further, participants were randomized to receive a placebo or an L. reuteri inoculum (of either strain) on day 4 of each diet period. Of the 41 subjects randomized, only 30 completed the intervention and were included in analyses.

Fiber intake doubled during the restore diet, on average, compared to the usual diet, while saturated fats reduced significantly; energy intake did not significantly differ. Supplementation of L. reuteri had no detectable impact on safety-related measures; the restore diet increased creatine levels and reduced the estimated glomerular filtration rate (eGFR), albeit within normal ranges.

The restore diet increased the daily number of bowel movements, softened stool consistency, and increased GI symptoms, such as flatulence, abdominal tension, and stomach ache. L. reuteri was detectable in fecal samples two days after administration by quantitative polymerase chain reaction (qPCR) and culture.

Both strains were undetectable by 12 to 17 days post-administration. The restore diet increased the abundance of PB-W1 only. PB-W1 cell numbers were significantly higher than DSM 20018T four and eight days post-administration.

The restore diet reduced alpha diversity within four days, which was sustained throughout the diet period; it also significantly altered the gut microbial community, assessed based on beta diversity differences between baseline and treatment points.

Further analyses revealed that the alpha diversity indices and inter- and intra-individual beta diversity differences returned to baseline levels by the end of the washout period or shortly after the initiation of the usual diet; this meant that the restore diet resulted in transient, reversible effects on the gut microbiome.

The restore diet increased short-chain fatty acid (SCFA) and acetate levels and reduced fecal pH, branched-chain fatty acids (BCFAs), and the BCFA-to-SCFA ratio.

In addition, untargeted metabolomics was performed to profile plasma metabolites. No significant metabolite shifts were detected between inoculum groups four days post-administration.

However, the restore diet had a significant global effect when metabolite shifts were compared to the usual diet. The restore diet significantly altered 31 metabolites, 90% of which are produced/modified by the microbiome or coproduced by the host and microbiome.

Next, the team investigated the effects of the restoration strategy on NCD risk markers. The restore diet decreased fecal calprotectin and plasma levels of total cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, C-reactive protein (CRP), and fasting glucose.

There was an increase in insulin sensitivity, with improvements in insulin resistance, mainly driven by the reduction in fasting glucose.

Conclusions

Together, the results offer vital insights into microbiome restoration. The researchers were able to reintroduce L. reuteri PB-W1 in one participant. A single dose of L. reuteri had no detectable impact on microbiome ecology, chronic disease risk markers, and plasma metabolome.

The restore diet decreased microbiome diversity, and the effects on microbiome composition and functional features varied highly among participants.

Moreover, the restore diet beneficially altered various plasma metabolites, many of microbial origin, which are implicated in NCDs. It also had several cardiometabolic benefits, such as weight loss and decreases in fasting plasma glucose, LDL, and CRP.

Notably, microbiome features with established roles in NCD pathology were redressed by the restore diet, several of which predicted cardiometabolic benefits.

Journal reference:
Tarun Sai Lomte

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.

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