How your diet and probiotics can improve vaccine effectiveness

Could your gut bacteria decide how well vaccines work? A new study reveals how diet and probiotics could hold the key to stronger, longer-lasting immune protection.

Study: Diet, microbiome, and probiotics establish a crucial link in vaccine efficacy. Image Credit: Helena Nechaeva / Shutterstock

A recent study published in the journal Critical Reviews in Microbiology reviewed how probiotics and diet modulate the gut microbiome to shape immune responses and vaccine efficacy.

Vaccines are critical to curb the spread of infectious diseases. Low vaccination rates below the threshold for achieving herd immunity lead to the (re-)emergence of preventable diseases. However, achieving herd immunity could prove challenging for highly infectious agents, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), measles virus, and influenza virus, due to viral evolution, heterogeneity in vaccine-induced immunity, and changing demographics.

Besides, the host microbiome influences immune system development and function. The gut microbiota could influence host vaccine response and immunocompetence. As such, a balanced gut microbial community (gut eubiosis) is vital for an optimal immune system and maximizing specific immune responses to vaccines. Therefore, the gut microbiome could be targeted to augment vaccine responses. Diet is a crucial determinant of the gut microbiota composition. Notably, the nutritional components of a diet can explicitly select microbes that utilize such nutrients or their metabolites. As such, modifying dietary constituents could modulate the composition of the gut microbiota and thereby alter vaccine responses. In the present study, researchers reviewed the evidence on the links between gut microbiota composition and vaccine responses, emphasizing how dietary interventions and probiotics shape this relationship.

Gut microbiota and determinants

The colonization of the gut was believed to start at birth, with a sterile fetal gastrointestinal (GI) tract before birth. However, recent studies indicate that the amniotic and placental microbial communities may initiate gut colonization in utero. During birth, the newborn comes in contact with the environment, shaping the neonatal microbiome. The gut microbiome remains vulnerable to environmental changes in the first two years of life.

The microbial community gradually matures and becomes stable in adulthood, particularly at the phylum level. Actinobacteria, Proteobacteria, Firmicutes, Fusobacteria, Verrucomicrobia, and Bacteroidetes are the predominant phyla of the gut microbiota. This composition does not change with acute perturbations; slight changes are usually rapidly restored. However, prolonged exposure to environmental hazards, modern lifestyle factors, and stress may lead to dysbiosis.

Besides, the mode of delivery influences neonatal gut microbiota composition. That is, vaginally delivered newborns have a higher predominance of Prevotella, Bifidobacterium, and Lactobacillus, while those born through cesarean section have a higher colonization of hospital-related opportunistic pathogens. Formula-fed infants show lower levels of beneficial Bifidobacterium compared to breastfed infants, underscoring the role of early nutrition.

Links between gut microbiome and vaccine responses

Various studies have reported prominent associations between the gut microbiome composition and vaccine efficiency in infants. For instance, a Nicaraguan survey found higher Proteobacteria levels in infants who did not seroconvert to rotavirus vaccine. Further, gut microbiome differences —including higher Bifidobacterium and Lactobacillus in responders— were reported between non-responders and responders to rotavirus vaccine in Ghanaian infants.

In addition, massive heterogeneity in responses to yellow fever, hepatitis B, influenza, and diphtheria-tetanus-pertussis vaccines have been observed in adults, especially in older people. Specifically, the predominance and diversity of commensal microbes decline with age, but the presence of opportunistic pathogens increases. Further, studies have illustrated associations between the gut microbiome and coronavirus disease 2019 (COVID-19).

A study observed significant changes in the gut microbiome composition in COVID-19 patients, with a higher abundance of opportunistic pathogens and a reduced abundance of commensal symbionts. A recent study found that specific gut microbes are associated with poor long-term immunogenicity after three CoronaVac doses. Further, short-chain fatty acid (SCFA)-producing microbes —which enhance B-cell metabolism and antibody production— were associated with prolonged antibody half-life after COVID-19 mRNA vaccination. However, some contradictory findings—such as infants with similar microbiomes showing differing vaccine responses—highlight the complexity of microbiome-immune interactions.

Dietary interventions and probiotics modulate gut microbiome and immune responses

Dietary patterns and constituents affect the function and composition of the gut microbiome. For instance, a protein-rich diet increases the Oscillibacter and Akkermansia muciniphila populations and decreases the Bifidobacterium and Lactococcus lactis populations. It also influences the clonal expansion of specialized intestinal T cells and protects against food allergy.

A Mediterranean or vegetarian fiber-rich diet —particularly with fibers like inulin and pectin— promotes the growth of SCFA-producing microbes, which, in turn, could modulate immune responses. These dietary patterns, shaped by cultural and regional habits, uniquely influence microbial communities. Further, higher fat intake correlates with lower gut microbial diversity and elevated abundance of Clostridium bolteae and Eubacterium rectale. A high-fat diet also promotes lipopolysaccharide-producing microbes, alters intestinal cytokines, and increases gut permeability, impairing mucosal immune defense. Animal-based foods, such as red meat and lard, may worsen dysbiosis, though fish oil (rich in omega-3 fatty acids) shows protective effects.

Importantly, dietary micronutrients like vitamin D, zinc, and iron also modulate gut health and vaccine responses. For example, excessive iron intake may promote dysbiosis, while zinc and vitamin D deficiencies are linked to impaired immunity.

Probiotics —especially strains like Bifidobacterium longum and Lactobacillus rhamnosus GG— exhibit robust immunomodulatory and adjuvant responses by regulating host T cells, chemokines, cytokines, antibody secretion, and mucosal immunity. The supplementation of prebiotics and probiotics can boost immunity and potentially increase the effectiveness of vaccines. A meta-analysis found beneficial effects of probiotics on vaccine response, with robust responses for oral vaccines though outcomes vary by strain, dosage, and host factors.

Concluding remarks

Together, gut microbiome composition is a critical immune health determinant. Evidence underscores the importance of gut eubiosis in enhancing vaccine response throughout life. Older adults and infants are at a higher risk of gut dysbiosis and altered vaccine responses, warranting special attention. Notably, the interactions of other gut microbes, such as fungi (e.g., Candida), protozoa, archaea (e.g., Methanobrevibacter), and viruses (e.g., bacteriophages), remain unexplored. Interlinking the microbiome, diet, vaccines, and probiotics will provide new research opportunities for precision vaccination strategies.