In a recent study published within the Nature Communications Journal, researchers explored the role of food regimen in controlling the structure and performance of the gut via chemical environment modulation.

To check this, they investigated the consequences of host food regimen supplements, especially fiber, in altering the harmful impacts of antibiotic-induced gut dysbiosis (AID).

Study: Fiber supplementation protects from antibiotic-induced gut microbiome dysbiosis by modulating gut redox potential. Image Credit: TatjanaBaibakova/Shutterstock.com

Background

The study utilized in vivo murine models and next-generation sequencing approaches to elucidate their observations’ chemical and mechanical underpinnings.

Their results revealed that dietary fiber could modulate gut bacterial metabolism, safeguarding against AID via a redox-driven mechanism.

Moreover, fiber helped conserve a majority of helpful gut bacteria and hasten their recovery after the antibiotic course in comparison with other dietary regimes and probiotic supplements.

AID and food regimen

For the reason that discovery of penicillin in 1928, antibiotics have played a vital role in treating microbial diseases. Nevertheless, given their mode of motion, antibiotics often cause collateral damage to the helpful gut microbiome, leading to antagonistic conditions, including antibiotic-induced gut dysbiosis (AID).

Dysbiosis is a typical and sometimes severe ailment, leading to inflammatory bowel disease, infection, aberrant immune function, and metabolic disorders.

Research has explored the consequences of probiotic supplements and oral drug adsorbers to counteract AID. Still, these approaches may increase gut disequilibrium (for probiotics) or reduce antibiotic efficacy, prompting the necessity for alternative AID therapies.

Studies have found that food regimen can have a major effect on predictable biochemical reactions occurring within the gut. The precise carbon source in food can influence which electron acceptors reach the gut microbiota.

Western diets, traditionally wealthy in sugar, are rapidly absorbed in hosts’ digestive tracts. This leads to limited carbon reaching the gut, which microbes are forced to compete for, altering their mode of motion to focus on carbon within the intestine’s mucosal lining damaging the gut.

Recent work has suggested that modifying metabolism may protect gut microbiota from antibiotic stress. In vivo, murine models have shown that repressing microbial metabolism reduces antibiotic susceptibility.

Studies specializing in the role of food regimen on AID have found that dietary fibers, including Xanthan gum, can reduce antibiotic impacts on gut microbiome richness post-antibiotic treatment.

Conversely, Western diets wealthy in sugars and fat have been shown to exacerbate AID. Nevertheless, the mechanisms underlying the associations between food regimen and AID remain hypothetical and vague.

In regards to the study

The current study uses next-generation metagenomic and metatranscriptomic sequencing to analyze gut microbiota composition and performance in high resolution.

Researchers then combined this data with sensitive chemical measurements of the gut environment to elucidate the enrichment of observed metabolic pathways.

4-week-old C57BL/6 mice (female, all with AID) were divided into case and control cohorts. The controls were fed a modified food regimen utilizing glucose because the exclusive carbon source. In contrast, the cases were fed a food regimen devoid of glucose but wealthy in seven dietary fibers (inulin, pectin, dextrin, levan, arabinoxylan, beta-glucan, and cellulose).

Glucose is a rapidly absorbed monosaccharide expected to induce carbon stress on the gut microbiome. At the identical time, the fiber cocktail is slow digesting, expected to achieve and be bacterially processed within the gut.

Each cohorts were fed their respective diets for every week before being administered a course of the antibiotic amoxicillin.

Longitudinal 16S rRNA sequencing of murine feces was used to discover the optimal time of fiber supplementation on recovery post-antibiotic treatment.

Metatranscriptomic and metagenomic sequencing of cecal contents on days one and five post-treatment was employed to broaden the gut microbiota’s taxonomic and functional resolution. Metatranscriptomic sequencing was moreover used to find out alterations in metabolic functions within the gut.

The HMP Unified Metabolic Evaluation Network (HUMAnN3.0) database and the MaAsLin2 R package were used to analyze diet-associated changes in biochemical processes along the bioenergetic scale, disentangling metabolism, and bioenergetics.

Linear discriminant analyses were used to discover pathway-level metabolic signatures. Researchers finally measured the chemical redox potential in murine cecal contents to elucidate the physiological manifestation of observed metatranscriptomic and metagenomic alterations.

Study findings

The current study found that a high-fiber food regimen conveys protection against antibiotics and, subsequently, AID before, during, and post-antibiotic treatment. In any respect stages, a high-fiber food regimen resulted in lower microbiome diversity loss and improved recovery post-treatment.

“These observations imply that superb modification to food regimen can affect microbiome recovery post-antibiotic treatment. From a translational perspective it is especially helpful that supplementation on the time of antibiotic administration is as effective as prior to treatment.”

Metatransciptomic and metagenomic sequencing revealed that fiber directly reduces AID symptoms, while a glucose-rich food regimen exacerbates the condition. Intestinal histopathology and bacterial load were consistent within the case-cohort on day five post-antibiotic treatment, elucidating the protective effects of fiber.

In contrast, control mice consumed the glucose food regimen depicted significant reductions of their alpha diversity on each day one and, to a more considerable extent, day five of treatment. The glucose food regimen was further observed to shift gut microbial species composition, increasing Proteobacterial load. Previous work has found associations between Proteobacteria and AID, implying the worsening of the condition.

Metatranscriptomic evidence showed that high-fiber diets resulted in gut microbiomes shifting their metabolic pathways to those assigned to fatty-acid metabolism, dormancy, and carbon fixation. In contrast, high-glucose diets moved pathways to those involved with respiratory metabolism.

“Basically, energetic metabolism is related to increased susceptibility while metabolic dormancy confers protection. This further adds to the information displaying that glucose supplementation promotes an aerobic inflammatory GI environment.”

Biochemical process analyses revealed that fiber in food regimen may increase fermentative metabolism and buffer the redox potential of the gut. In contrast, the glucose food regimen depicted an upregulation within the transcription of pathways involving nitrate and oxygen as terminal electron acceptors.

These results imply that fiber can promote protective fermentative metabolism by reducing gut redox potential, thereby protecting against damaging respiratory metabolism related to antibiotic treatment.

Conclusions

In the current study, researchers used murine AID models consumed high-glucose and high-fiber diets to analyze the effect of modifiable diets on AID post-antibiotic treatment. These results were merged with metatranscriptomic and metagenomic sequencing to elucidate the functional and histopathological changes these diets confer on gut microbial assemblies.

This study reveals that high-fiber diets can conserve gut microbiota richness and alter their biochemical pathway associations to those favoring fermentation and dormancy, conferring protection against the antagonistic effects of AID post-antibiotic treatment.

In contrast, glucose-rich diets were found to cut back microbiome alpha diversity and shift biochemical pathways to those favoring oxidative respiration, damaging the gut lining and exacerbating AID.

“This work makes essential strides in linking changes in diet-induced redox potential and resulting microbial activity to differential antibiotic susceptibility. The following essential steps are to ascertain causation between changes in redox potential and antibiotic susceptibility within the context of the host. Future studies can goal investigation towards the consequences of food regimen directly on host cell metabolism because it pertains to microbiome changes and determine if the observed differences translate to male mice.”