Changes in the gut microbiota are associated with inflammatory diseases, prompting researchers to investigate whether targeted interventions can help manage these conditions. However, evidence suggests that microbiota-based therapies may need to be tailored to individual patients rather than applied through a one-size-fits-all approach.

The gut microbiota consists of trillions of microorganisms that live in the intestine and play a key role in maintaining physiologic balance. Under normal conditions, it helps maintain the integrity of the intestinal barrier, modulates immune responses, and produces beneficial substances such as short-chain fatty acids (SCFAs), which have anti-inflammatory effects.

When dysbiosis occurs, this balance is disrupted, and the intestinal barrier can become more permeable. This can stimulate immune cells in the intestinal mucosa to release inflammatory molecules and allow bacterial components to enter the bloodstream, potentially triggering a systemic inflammatory response.

Speaking with El Médico Interactivo, part of the Medscape Professional Network, José Antonio Cornejo García, PhD, senior researcher in the Allergy Research Group, Biomedical Research Institute of Malaga and Nanomedicine Platform (IBIMA-Plataforma BIONAND) in Malaga, and Marina Pérez Gordo, PhD, director of the Department of Basic Medical Sciences at the School of Medicine, Facultad de Medicina, Universidad San Pablo-CEU in Madrid, Spain, said, “We know that inflammatory diseases are associated with alterations in the gut microbiota. Certain patterns of dysbiosis recur across different diseases, such as reduced microbial diversity, lower production of SCFAs, and disruption of the intestinal barrier. However, we cannot conclude that dysbiosis causes these diseases. Rather, it appears to be part of a complex system in which multiple factors interact, including genetics, the environment, and each individual’s immune response.” Against this background, therapeutic modulation of the microbiota aims to restore microbial diversity and promote an environment that supports immune tolerance.

These specialists are the authors of a review describing the main strategies currently being investigated to modify the microbiota, including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). However, “the level of evidence supporting each of these strategies varies widely, and many are still in the early stages of research,” Cornejo García and Pérez Gordo noted, citing several examples.

In multiple sclerosis, some trials of probiotics have shown improvements in certain inflammatory and clinical parameters, whereas FMT has shown promising results in normalizing intestinal permeability in pilot studies.

Studies on rheumatoid arthritis have found that some conventional treatments, including methotrexate and anti-TNF agents, can partially modify dysbiosis. However, it is not yet known whether these changes directly contribute to the control of inflammation. Evidence of FM remains largely anecdotal, with only a single published case.

Research on eye diseases has also produced promising results, particularly with probiotics and certain postbiotics for dry eye. In food allergies, some probiotics and synbiotics, including the combination of Bifidobacterium breve and fructooligosaccharides in infant formulas, have been shown to modify the microbiota and promote a profile more closely associated with tolerance. However, the evidence remains insufficient to establish general recommendations because of differences in study design, strains used, and timing of administration.

Taken together, these findings suggest that future microbiota intervention trials should move toward personalized modulation with the aim of modifying specific functions of the microbial community while taking individual characteristics into account.

The researchers also emphasized that such interventions should be considered from the early years of life. This is one of the most consistent findings in the reviewed literature. “The early colonization of gut microbiota is critical for health, particularly during the first 2 years of life, when the first interactions with external stimuli occur and the intestinal and immune systems develop. Disruptions during this early period, such as the use of antibiotics during pregnancy or the first year of life, have been associated with a higher subsequent risk of developing asthma and other atopic conditions,” the researchers said.

One finding that they considered particularly interesting, based on the CORAL cohort study and reported in their review, was that vertical transmission from mother to baby appears to play a greater role in the development of allergies than horizontal environmental exposure. This was observed during the social restrictions of the COVID pandemic, which significantly reduced environmental microbial exposure, yet the prevalence of allergies did not change significantly.

Healthy Microbiota

The researchers also discussed factors associated with maintaining healthy microbiota. Cornejo García and Pérez Gordo noted that, although the article synthesizes associations reported in scientific literature rather than serving as a lifestyle guide, it offers several relevant insights.

Generally, greater microbial diversity is associated with better intestinal barrier protection against pathogens and reduced inflammation. The review also identified dietary patterns associated with microbiota that promote a less inflammatory environment.

For example, a diet higher in fiber and lower in animal products is associated with a higher proportion of SCFA-producing bacteria, which play a protective role against airway inflammation. Similarly, a diet rich in fiber and lean protein is associated with a lower risk for diabetic retinopathy. A low-glycemic index diet has also been associated with a lower risk for macular degeneration. In contrast, antibiotic use during pregnancy and early childhood has been consistently associated with a higher risk for childhood asthma.

The study aims to provide an up-to-date overview of the evidence linking microbiota with inflammatory diseases while identifying the direction in which research should move.

Challenges

“One of the main challenges highlighted by the study is precisely to move beyond the description of disease-associated microbiota alterations toward the identification and validation of reproducible and clinically relevant biomarkers. To achieve this, it will be necessary to standardize both analytical protocols and interventions while, at the same time, integrating microbial information with metabolic, proteomic, epidemiological, and clinical data,” they noted.

The broader goal is to advance personalized and precision medicine, in which a patient’s microbial and metabolic profiles can help assess the risk, guide treatment, and monitor the response.

This approach is consistent with one of the objectives of the REI/RICORS Inflammatory Diseases Network, the organization behind the study, which is working to develop a common framework for standardizing biomarker analysis and validation and facilitating the incorporation of these biomarkers into clinical practice.

Cornejo García and Pérez Gordo reported having no relevant conflicts of interest.

This article was translated from El Médico Interactivo.