The gut microbiota is closely related to good health; thus, there have been extensive efforts dedicated to improving health by controlling the gut microbial environment. Probiotics and prebiotics are being developed to support a healthier intestinal environment. However, much work remains to be performed to provide effective solutions to overcome individual differences in the gut microbial community. This study examined the importance of nutrients, other than dietary fiber, on the survival of gut bacteria in high-health-conscious populations. We found that vitamin B1, which is an essential nutrient for humans, had a significant effect on the survival and competition of bacteria in the symbiotic gut microbiota. In particular, sufficient dietary vitamin B1 intake affects the relative abundance of Ruminococcaceae, and these bacteria have proven to require dietary vitamin B1 because they lack the de novo vitamin B1 synthetic pathway. Moreover, we demonstrated that vitamin B1 is involved in the production of butyrate, along with the amount of acetate in the intestinal environment. We established the causality of possible associations and obtained mechanical insight, through in vivo murine experiments and in silico pathway analyses. These findings serve as a reference to support the development of methods to establish optimal intestinal environment conditions for healthy lifestyles.

The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.

Besides promoting inflammation by mobilizing lipid mediators, group IIA secreted phospholipase A ₂ (sPLA ₂ -IIA) prevents bacterial infection by degrading bacterial membranes. Here, we show that, despite the restricted intestinal expression of sPLA ₂ -IIA in BALB/c mice, its genetic deletion leads to amelioration of cancer and exacerbation of psoriasis in distal skin. Intestinal expression of sPLA ₂ -IIA is reduced after treatment with antibiotics or under germ-free conditions, suggesting its upregulation by gut microbiota. Metagenome, transcriptome, and metabolome analyses have revealed that sPLA ₂ -IIA deficiency alters the gut microbiota, accompanied by notable changes in the intestinal expression of genes related to immunity and metabolism, as well as in the levels of various blood metabolites and fecal bacterial lipids, suggesting that sPLA ₂ -IIA contributes to shaping of the gut microbiota. The skin phenotypes in Pla2g2a ^–/– mice are lost (a) when they are cohoused with littermate WT mice, resulting in the mixing of the microbiota between the genotypes, or (b) when they are housed in a more stringent pathogen-free facility, where Pla2g2a expression in WT mice is low and the gut microbial compositions in both genotypes are nearly identical. Thus, our results highlight a potentially new aspect of sPLA ₂ -IIA as a modulator of gut microbiota, perturbation of which affects distal skin responses.

Objective: Food addiction is a multifactorial disorder characterised by a loss of control over food intake that may promote obesity and alter gut microbiota composition. We have investigated the potential involvement of the gut microbiota in the mechanisms underlying food addiction. Design: We used the Yale Food Addiction Scale (YFAS) 2.0 criteria to classify extreme food addiction in mouse and human subpopulations to identify gut microbiota signatures associated with vulnerability to this disorder. Results: Both animal and human cohorts showed important similarities in the gut microbiota signatures linked to food addiction. The signatures suggested possible non-beneficial effects of bacteria belonging to the Proteobacteria phylum and potential protective effects of Actinobacteria against the development of food addiction in both cohorts of humans and mice. A decreased relative abundance of the species Blautia wexlerae was observed in addicted humans and of Blautia genus in addicted mice. Administration of the non-digestible carbohydrates, lactulose and rhamnose, known to favour Blautia growth, led to increased relative abundance of Blautia in mice faeces in parallel with dramatic improvements in food addiction. A similar improvement was revealed after oral administration of Blautia wexlerae as a beneficial microbe. Conclusion: By understanding the crosstalk between this behavioural alteration and gut microbiota, these findings constitute a step forward to future treatments for food addiction and related eating disorders.

Effective and safe vaccine adjuvants are needed to appropriately augment mucosal vaccine effects. Our previous study demonstrated that lipopolysaccharide (LPS) from Peyer’s patch resident Alcaligenes stimulated dendritic cells to promote the production of mucosal immunity-enhancing cytokines (e.g., IL-6 and BAFF), thus enhancing antigen-specific immune responses (including IgA production and Th17 responses) without excessive inflammation. Here, we chemically synthesized Alcaligenes lipid A, the biologically active part of LPS, and examined its efficacy as a nasal vaccine adjuvant for the induction of protectively immunity against Streptococcus pneumoniae infection. Mice were nasally immunized with pneumococcal surface protein A (PspA) as a vaccine antigen for S. pneumoniae, together with Alcaligenes lipid A. Alcaligenes lipid A supported the generation of high levels of PspA-specific IgA and IgG responses through the augmentation of germinal center formation in the nasopharynx-associated lymphoid tissue and cervical lymph nodes (CLNs). Moreover, Alcaligenes lipid A promoted PspA-specific CD4⁺ Th17 responses in the CLNs and spleen. Furthermore, neutrophils were recruited to infection sites upon nasal infection and synchronized with the antigen-specific T and B cell responses, resulting in the protection against S. pneumoniae infection. Taken together, Alcaligenes lipid A could be applied to the prospective adjuvant to enhance nasal vaccine efficacy by means of augmenting both the innate and acquired arms of mucosal immunity against respiratory bacterial infection.

Alcaligenes spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that Alcaligenes-derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflammation. Lipid A is one of the components responsible for the biological effect of LPS and has previously been applied as an adjuvant. Here, we examined the adjuvant activity and safety of chemically synthesized Alcaligenes lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus Alcaligenes lipid A relative to those that were immunized with OVA alone. In addition, Alcaligenes lipid A promoted antigen-specific T helper 17 (Th17) responses in the spleen; upregulated the expression of MHC class II, CD40, CD80, and CD86 on bone marrow-derived dendritic cells (BMDCs); enhanced the production of Th17-inducing cytokines IL-6 and IL-23 from BMDCs. Stimulation with Alcaligenes lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, Alcaligenes lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that Alcaligenes lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination.