The shift toward plant- and fungal proteins is driven by environmental and public-health concerns, but wider adoption is constrained by poor sensory quality, limited techno-functionality, and variable nutritional performance. Fermentation has re-emerged as a versatile processing approach because it can improve flavor and texture while remaining compatible with clean-label food design. Yet the effects of fermentation designed for alternative proteins on host physiology remain largely unexplored. This chapter examines how fermentation modifies plant- and fungal-protein foods at multiple levels and how these changes may translate into health-relevant outcomes. After outlining the major chemical and physical transformations induced by fermentation, the chapter moves beyond the traditional focus on nutrients and bioactive metabolites to consider how fermentation-driven changes in flavor and food structure influence gastrointestinal signaling and digestion. Particular attention is given to how in situ production of exopolysaccharides (EPS) during fermentation reshapes matrix organization and governs the delivery of food components along the gastrointestinal tract, where they can be utilized by the host or serve as substrates for gut microbes in complex trophic chains. Accordingly, the gut microbiome provides a key interface for these processes by integrating both chemical and physical cues from foods after ingestion, while also mediating how these cues translate into physiological responses, thereby serving as a composite readout of food properties and host physiology. By highlighting what is known and where evidence is emerging, this chapter aims to support the future rational design of fermented plant- and fungal-protein foods for both product performance and health.

Segmented filamentous bacteria (SFB) describe morphologically similar gut commensals found in mammals, fish and birds. In mice, SFB intimately colonizes the ileal epithelium at the time of weaning and elicits a strong pleiotropic immune activation that fosters colonization resistance while augmenting disease severity in various disease models. SFB is therefore critical in both health and disease but information regarding SFB in humans remains limited. Here, we first identify and characterize a human SFB species with SFB-specific morphology, including the hook-like tip structure that mediates attachment, and unique genome features, including a starch and glycogen degradation module. This species, which we name Anisomitus miae and establish as the nomenclature type for the SFB genus, is within a SFB lineage common across Africa. We then bioinformatically identify, based on the 16S rRNA gene V3-V4 variable region sequence, four major, and two minor, human SFB lineages in forty-four countries distributed across all six inhabited continents. We provide evidence towards the co-colonization potential of the SFB lineages and their colonization dynamics, including a potent but short-lived colonization peak in children between one to five years of age. This study establishes the presence of multiple SFB species in the human population and SFB as a minor but wide-spread group of commensals in humans.

OBJECTIVE:This study investigates whether live Akkermansia muciniphila MucT supplementation can counteract obesity and metabolic dysfunctions induced by a high-fat diet (HFD) by modulating intestinal mucus production, secretion and composition. DESIGN:C57BL/6J mice were fed an HFD with or without live A. muciniphila MucT (2 × 108 CFU per day) supplementation or a control diet for 6 weeks. Body weight, fat mass gain and metabolic markers were measured. Intestinal mucus characteristics were assessed via gene expression analysis of mucins and analysed mucin glycosylation by tandem mass spectrometry (MS/MS). RESULTS:Mice receiving live A. muciniphila MucT exhibited reduced body weight gain and fat mass accumulation compared to HFD controls, without changes in muscle mass. A. muciniphila improved gut barrier integrity by increasing antimicrobial peptide expression in the jejunum and in the colon of HFD-fed mice. Furthermore, live A. muciniphila MucT influenced markers of goblet cell differentiation and restored the expression of mucin markers altered by HFD. Specifically, live A. muciniphila MucT counteracted HFD-induced mucin 3 (Muc3) expression depletion in the colon. Although the overall mucus thickness was not affected by live A. muciniphila MucT, the bacteria significantly modulated mucin glycans composition. Live A. muciniphila MucT did not change the gut microbiota composition. CONCLUSION:These findings highlight the protective effects of live A. muciniphila MucT against diet-induced metabolic dysfunctions by modulating adiposity, mucus layer composition, and glycan profiles. This reinforces its potential as a therapeutic strategy for metabolic disorders associated with gut microbiota alterations.

AIM:Plasma C-reactive protein (CRP) is widely used to assess neonatal infection, although mild, unexplained elevations are common in healthy newborns. We examined relationships between non-infectious CRP levels and neonatal factors, and early gut microbiota composition in term infants. METHODS:This study was conducted within the prospective Finnish HELMi birth cohort. We included 105 full-term infants with plasma CRP levels measured during the first four postnatal days. Perinatal data were retrieved from medical records. Faecal samples collected at 3 weeks underwent 16S rRNA gene sequencing. RESULTS:Initial CRP level was elevated (≥ 3 mg/L) in 57% of infants, with no diagnosis of an infection. CRP levels were not associated with maternal group B Streptococcus status, intrapartum antibiotics, early neonatal complications or delivery mode, except for higher levels on day three after spontaneous versus induced vaginal delivery. Gut microbiota composition at 3 weeks differed according to CRP status, with family Acidaminococcaceae being less prevalent when CRP was elevated. Birth mode, antibiotic exposure and umbilical artery pH in the asphyxia range (≤ 7.1) were associated with distinct microbial profiles. CONCLUSIONS:Mild CRP elevations in term newborns were associated with differences in early gut microbiota composition but poorly explained by perinatal clinical factors.

ABSTRACT To advance our understanding of the genomic stability of Akkermansia muciniphila, its type strain MucT was grown for over 1,000 generations at five different culturing conditions, followed by the isolation of single colonies and their subsequent genomic DNA sequencing, physiological, and functional analysis. Notably, not a single mutation was found in the genomes using our sequencing approach of the dozen strains isolated after growth for 1,000 generations in media containing porcine gastric mucin, either grown with or without shaking. Similarly, strains isolated from cultures grown in minimal medium containing high or low N-acetylglucosamine, or low N-acetylglucosamine containing 1% ox bile, exhibited very low mutation rates between 2.1 × 10−10 and 8.6 × 10−11 per nucleotide per generation. From these, a total of five unique strains were obtained that contained one or more nucleotide variations. Subsequent analysis and characterization revealed that two of the five strains included a G duplication in a nonanucleotide homopolymer G region in the gene with the locus tag Amuc_1413, resulting in a frameshift and a subsequent loss of mucin binding capacity. Analysis of published genomes of Akkermansia spp. confirmed the instability of this nonanucleotide G region in this Amuc_1413 gene, predicted to be involved in exopolysaccharide export. These findings provide valuable insight into the stability of the A. muciniphila genome and identify phase variation as a mechanism that can explain some of the earlier reported heterogeneity. We conclude that A. muciniphila MucT has large genomic stability under long-term culturing conditions and identified the Amuc_1413 protein as essential for mucus binding.IMPORTANCEAkkermansia muciniphila MucT has emerged as a next-generation beneficial microbe due to its capacity to improve gut barrier function in mouse models and humans. To assess the potential of A. muciniphila MucT for industrial applications, we studied the genomic stability by cultivating different growth conditions for over 1,000 generations. We found that the genome of A. muciniphila MucT is highly stable when grown on mucin medium and relatively stable when grown in industrial media. Additionally, we characterized the obtained mutants that identified phase variation as a mechanism operating in A. muciniphila, which allowed us to identify the gene with the locus tag Amuc_1413, encoding a protein involved in exopolysaccharide production, to be involved in mucus binding.

In a nationwide study (PREVENT) addressing the longitudinal development of 253 infants in Sweden (744 stool samples), we used deep metagenomic sequencing to determine the bacterial composition. We focused on the 200 fecal samples collected during the first 6 months of life from 146 infants who were predominantly breast-fed. Unsupervised analysis of these infants’ microbial gut composition revealed three distinct foundational community types: CT1 infants had high Bifidobacterium spp. levels, CT2 infants had only B. breve at low abundances but high Bacteroidota, and CT3 infants had virtually no Bifidobacterium spp. but elevated levels of pathobionts. Surprisingly, we observed a clear bimodal distribution of Bifidobacterium spp., the canonical taxa associated with early-life colonization. Sixty samples from predominantly (58%) vaginally-born infants did not contain any detectable gut Bifidobacterium genomes (<0.001%; confirmed by 16S rRNA amplicon sequencing and qPCR analysis). The remaining 140 samples showed high relative Bifidobacterium abundance (median 70%), notably including B. breve, B. longum subsp. longum and B. longum subsp. infantis. Infants lacking Bifidobacterium spp. showed crying after feeding and contained an unusual gut microbiota composition, dominated by known pathobionts such as Clostridium neonatale or Klebsiella michiganensis. The metagenome-based predicted functional capacity of the gut of infants lacking Bifidobacterium spp. showed an increased levels of potentially undesired genes involved in mucus degradation, sporulation processes, and flagella production, while the Bifidobacterium-colonized infants were enriched in starch degradation, glutamate transport, and aromatic amino acid production. Notably, we found that a pathway for the production of lactate derivatives of tryptophan and other aromatic amino acids with anti-inflammatory activity was more abundant in the latter group. Our results indicate that infants lacking Bifidobacterium spp. contain unusual gut microbiota architecture and functions that are associated with health issues. This pattern is more prevalent in PREVENT than observed in many other studies, underscoring the importance of early testing, while long-term follow-up and potential nutritional advice should be addressed in future studies.Clinical Trials NCT06285630.

Obesity and excess body weight in companion animals represent significant and growing health concerns. Accumulating evidence indicates that obesity-associated metabolic and inflammatory dysfunction may be mitigated through dietary modulation of host-microbiome interactions. In this controlled dietary intervention study, healthy Beagle dogs were fed a commercially available high-caloric, protein-, and lipid-enriched diet at three times their daily energy requirement for 8 weeks and orally supplemented with either pasteurized Akkermansia muciniphila MucT or a placebo. Supplementation reduced weight gain and attenuated the high-caloric diet-induced expansion of Peptacetobacter hiranonis and Collinsella spp. compared to controls. Pasteurized A. muciniphila-treated animals exhibited reduced circulating pro-inflammatory cytokines and a marked decrease in fecal calprotectin levels, indicative of reduced mucosal inflammation. Longitudinal modeling identified treatment-associated alterations in inflammatory markers, while integrative multi-omics factor analysis (MOFA) and redundancy analysis (RDA) revealed coordinated changes across inflammatory, metabolic, and bile acid profiles that distinguished placebo- and pasteurized A. muciniphila-treated animals under high-caloric feeding conditions. These changes were accompanied by normalization of circulating bile acid profiles, particularly reductions in microbiome-derived secondary bile acids and oxo-derivatives associated with metabolic dysfunction. Together, these findings provide integrative insight into the immune-metabolic effects of pasteurized A. muciniphila MucT in dogs under high-caloric feeding conditions and support its potential as a dietary intervention to mitigate obesity-associated dysfunction in companion animals. As this is an exploratory proof-of-concept study conducted in a limited number of animals under controlled feeding conditions, further validation in larger and more diverse companion animal populations is warranted.IMPORTANCEObesity in pet dogs is increasingly recognized not only as a condition of excess body fat but as a chronic inflammatory disorder with profound metabolic consequences. This study demonstrates that dietary supplementation with pasteurized Akkermansia muciniphila MucT can counteract the adverse effects of a high-caloric diet in dogs by reducing body weight gain, preventing inflammation, and restoring bile acid homeostasis. These results highlight the therapeutic potential of gut-targeted nutritional strategies for managing obesity in companion animals and introduce A. muciniphila MucT as a safe, effective postbiotic with translational relevance for pet health.

BACKGROUND AND AIMS:Compromised bowel function and altered gut microbiota may disrupt gut-liver axis in short bowel syndrome (SBS), contributing to the development of intestinal failure-associated liver disease (IFALD). We conducted a multi-omics study integrating data from gut microbiota and liver transcriptomes with serum bile acids and clinical data in pediatric SBS-IF. METHODS:Fifty-nine pediatric SBS-IF patients provided 177 fecal samples, 100 during parenteral nutrition (PN) and 77 after weaning off PN. Gut microbiota was analysed using 16 S rRNA amplicon sequencing and sequence-based prediction of functional profiles, liver transcriptome using bulk RNA sequencing of selected liver biopsies (n = 31), and serum bile acids with mass spectrometry and surrogates of intestinal integrity with ELISA (n = 67). Results were related to liver histopathology and clinical outcomes and compared to healthy controls. RESULTS:Besides markedly reduced richness and diversity of intestinal microbiota, unsupervised clustering on pathway abundances revealed five principal clusters dominated by Escherichia, Klebsiella, Lactobacillus, Veillonella, and Faecalibacterium spp. that are associated with different metabolic processes. Clusters were segregated by residual bowel length, serum citrulline, PN dependency, and intestinal anatomy. Faecalibacterium predominated (67%) after achieving enteral autonomy, whereas PN dependency, short remaining bowel, and low citrulline levels were linked to the Lactobacillus-dominant cluster. End-enterostomy was associated with the Klebsiella and Escherichia dominant clusters. The Lactobacillus-dominant cluster was characterized by overexpression of bile acid metabolism pathway genes, and associated with elevated serum unconjugated chenodeoxycholic acid, which correlated inversely with histological cholestasis (r = -0.435, P = 0.003) and portal inflammation (r = -0.507, P < 0.001). SBS-IF livers showed activation of bile acid metabolism including CYP7A1, alongside increased serum C4. CONCLUSIONS:Pediatric SBS-IF is characterized by distinct microbiota clusters linked to clinical phenotype and bile acid metabolism, highlighting contribution of gut-liver crosstalk to IFALD pathogenesis and providing avenues for early diagnostics. CLINICAL TRIALS REGISTRATION NUMBER:n/a.

Preclinical research suggests that the mucosal symbiont Akkermansia muciniphila prevents diet-induced obesity. In this randomized controlled trial, adults with overweight/obesity (n = 90) underwent an 8-week low-energy diet for ≥8% weight loss, followed by a 24-week healthy ad libitum diet with daily supplementation of pasteurized A. muciniphila MucT or placebo. The primary outcome was change in body weight during the maintenance period. Here we show that MucT led to lower body weight regain versus placebo at the end of the weight maintenance period (MucT: 1.2 ± 0.7 kg, placebo: 3.2 ± 0.4 kg, P = 0.012). Additionally, the MucT group had a greater net weight loss from baseline to end of maintenance than the placebo group (3.1 ± 0.7 kg, P = 0.009). Initial Akkermansia spp. abundance was associated with cardiometabolic response to MucT. No serious adverse events related to the treatment were observed. The relative short-term intervention and absence of groups receiving modified strains of MucT lacking active components are limitations that should be addressed in the future. Our findings suggest pasteurized A. muciniphila MucT as a strategy for weight loss maintenance. ClinicalTrials.gov: NCT05417360 .

Pasteurized Akkermansia muciniphila MucT was found to improve barrier function in preclinical models and a proof-of-concept study in obese and prediabetic adults. Here, we describe the results of a double-blind placebo-controlled multicenter (Ireland and Germany) trial in 142 adults with metabolic syndrome, with or without prediabetes. The primary endpoint of whole-body insulin sensitivity (Matsuda index) did not differ after 4-months of daily administration of capsules containing 30 billion cells of pasteurized A. muciniphila MucT compared to placebo in the intention-to-treat subjects. Subsequent exploratory analyses showed that 3-months intake of pasteurized A. muciniphila MucT already improved HOMA-based hepatic insulin sensitivity in prediabetic (12%; p = 0.05) and 63-y-or-older-age subgroups (p = 0.05) while increasing post-OGTT excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) over placebo (p < 0.01). Further analysis of the gut microbiota by deep metagenomic analysis showed minor effects of the intervention but revealed that the baseline microbial composition differed from that in matched healthy adults. We found that participants with low baseline Akkermansia gene counts experienced significant health improvements and GLP-1 excursion after 3-months of treatment with pasteurized A. muciniphila MucT over the placebo. These benefits included improved insulin sensitivity (as shown by Matsuda and HOMA-S indices) and GLP-1 excursion (post-OGTT) (p < 0.05), reductions in body weight (p = 0.06) and decreased trunk fat (p < 0.05). In conclusion, daily supplementation with pasteurized A. muciniphila MucT has the potential to improve health markers in overweight or obese normo- or dysglycemic adults with the most significant improvements in subjects with low baseline intestinal Akkermansia levels, who are apparently truly in need of this intervention. Clinical trial registration no.: NCT05114018 clinicaltrials.gov.

Purpose PREVENT 1 is a nationwide, prospective Swedish infant cohort established to characterise gut microbiome development during the first 2 years of life and to relate microbial trajectories to feeding, infections, growth and everyday well-being. The study integrates repeated infant stool sampling with shotgun metagenomics analysis with aligned parental questionnaires, stool photographs and infant cry recordings collected at three approximately 3-month intervals for each infant.Participants Families were recruited nationwide in Sweden from September 2023 through targeted digital channels. Eligible participants were term-born infants residing in Sweden and aged <1 year at enrolment. Baseline questionnaire data and stool samples were collected from 253 infants. Parents completed questionnaires covering socio-demographic characteristics and health, pregnancy and delivery, postnatal factors, infant environment, feeding and growth, infections and other health outcomes, gastrointestinal symptoms and everyday well-being.Findings to date Retention was high, with 248 families completing at least one follow-up questionnaire at Phase 2 and 243 at Phase 3. For stool samples, 250 infants provided at least two samples and 241 provided all three. At enrolment, 42.3% of infants were older than 7 months, 73.9% had weight-for-length z-scores in the normal range and exclusive breastfeeding at 4 months was reported for 58.9%.Future plans Three-phase sample and questionnaire data collection was completed in December 2024. Future analyses will examine microbiome features, resistome profiles and functional pathways in relation to antibiotic exposure, feeding, growth and infant health outcomes. Subject to ethical approval and participant consent, follow-up may include further stool collection and Swedish register linkage.Trial registration number NCT06285630.

Background Dysosmobacter welbionis is a recently discovered butyrate producer whose presence in stool correlates with improved metabolic health. Whether its abundance is reduced in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. Mechanistic insight into its butyrate production from myo-inositol, a dietary compound from fruits, beans, grains and nuts with metabolic benefits, is also limited.Objective To assess population-level distribution, relative abundance and strain diversity of D. welbionis in humans, and to elucidate its metabolic capacity to ferment myo-inositol into butyrate.Design We analysed several human cohorts for associations with liver health and evaluated D. welbionis J115T supplementation in a diet-induced steatosis mouse model. An antibody-guided anaerobic cell-sorting strategy enabled isolation of distinct strains. We combined 13C-labelled inositol isotopes with NMR, mass spectrometry, genomics and proteomics.Results We found that D. welbionis and two related species (D. hominis and D. segnis) are prevalent gut bacteria in the human gut. D. welbionis abundance was reduced in MASLD across two cohorts and inversely correlated with fibrosis score in a third cohort. Treatment with D. welbionis J115T improved glycaemia and hepatic steatosis in high-fat diet fed mice. We identified a non-canonical myo-inositol-to-butyrate fermentation pathway. 19 human strains were isolated, comparative genomics of 23 strains revealed an open pangenome (about 2100 core genes) including the full myo-inositol fermentation pathway.Conclusion D. welbionis possesses a unique, conserved route to convert dietary myo-inositol into butyrate, distinguishing it from other commensals and supporting its potential as a next-generation probiotic for metabolic and liver health.

The gut microbiome has been linked to colorectal cancer (CRC) development, with microbe-based classifiers distinguishing between CRC patients and healthy controls. However, there is a lack of studies addressing the utility of the microbiome in screening-relevant settings, including both precancers and CRC. In this Norwegian population-based study, we used fecal immunochemical test (FIT) leftovers from 1034 FIT-positive (i.e. positive for occult blood) screening participants for gut metagenome profiling using shotgun sequencing. Using comprehensive clinical, demographic, and lifestyle data, we modeled gut microbiome associations with CRC screening outcomes. Combining microbial profiles with quantitative FIT values improved detection of premalignant lesions beyond optimizing the FIT value alone, even after incorporating established CRC risk factors. Still, the FIT value maintained superior discriminative ability for CRC. We confirmed enrichment of bacteria such as Fusobacterium nucleatum and Peptostreptococcus stomatis in CRC. In contrast, other bacteria previously associated with the presence of CRC, including Hungatella hathewayi and Clostridium symbiosum, as well as pks-negative Escherichia coli, were enriched in those with no neoplastic findings, suggesting that in a FIT-positive population their presence may reflect other conditions causing intestinal bleeding rather than underlying neoplasia. Microbial profiles were predominantly associated with distal rather than proximal lesions. Together, our findings highlight the potential for microbial markers to improve FIT-based CRC screening, especially by differentiating those with premalignant lesions from those who test FIT-positive for other reasons.

Akkermansia muciniphila MucT was authorized by EFSA in 2021 to be commercialized as novel food in its pasteurized form, corresponding to what it is commonly referred to as a postbiotic. As for probiotics, which are commercialized as living cells, postbiotics also require their correct quantification during the production process. Here we describe the optimization of a flow cytometry-based protocol for the absolute counting of pasteurized A. muciniphila cells in high cell density and standardized industrial batches. Protocol optimization required a sample preparation set-up and the choice of the appropriate diluent for the efficient rehydration of freeze-dried cells to limit cell aggregates. The developed quantification protocol allowed a more efficient cell counting with a lower standard deviation and coefficient of variation (CV) as compared with microscope-based quantification. The optimized protocol was successfully applied in a mass balance calculation over the production process, a standard validation in every industrial process for microbial biomass production that starts from high cell density batches to achieve standardized batches with the target cell dosage. Finally, the inter-laboratory trial, carried out among six independent laboratories using a ring test design, revealed good accuracy and precision of the optimized quantification protocol with an average CV ranging between 12.3 and 24.1 % and a Z score max of 2.64. In conclusion, our study revealed that developed flow cytometry protocol is a fast, reliable, reproducible and accurate method for the enumeration of the pasteurized A. muciniphila MucT that could be applied with minor modifications to other postbiotics.

The human gut microbiota undergoes rapid development during early life. Sibling presence has been associated with altered infant microbiota composition and accelerated maturation, but distinguishing direct microbial transmission between siblings from confounding by maternal reproductive history (parity) remains challenging. We analysed >5,000 faecal samples from >800 mother-father-infant triads in the Finnish HELMi birth cohort to characterise microbiota patterns that could inform underlying mechanisms. While sibling presence was associated with accelerated microbiota maturation and modest compositional differences, infants who both had siblings (or both lacked siblings) were no more similar to each other than mixed pairs. Instead, infants with siblings exhibited non-specific convergence with adult microbiota profiles and contributed fewer unique genera to their family metacommunities (infant–mother–father triads). Multi-child families harboured smaller but compositionally distinct metacommunities. These patterns challenge simple models of direct sibling transmission and suggest that multiple factors associated with family structure may jointly influence infant microbiota development, though specific mechanisms remain unclear. ### Competing Interest Statement The authors have declared no competing interest.

Dietary proanthocyanidins (PACs) are polyphenols that promote a healthy gut microbiome. PACs are notable for their rich catechol moieties with high affinity for iron, enabling them to interfere with pathogens' iron uptake. PACs selectively increase the abundance of Akkermansia muciniphila, a symbiont known for supporting metabolic and immune health. We discovered that A. muciniphila MucT utilizes distinct iron-acquisition systems to take up iron sequestered by PACs, supporting its metabolic activity. Integrative proteomics and transcriptomics revealed that A. muciniphila has an active catechol-type siderophore-mediated iron uptake (Fe3+) system, involving membrane ATP-binding cassette transporters and lipocalins. Simultaneously, the expression of ferrous iron (Fe2+) transporters, zinc uptake, and iron storage proteins was upregulated. Administering iron-laden PACs in an iron-depleted medium restored the A. muciniphila growth to levels comparable to those in iron-amended conditions. This was associated with an increased expression of the A. muciniphila siderophore operon and lipocalin genes, indicating that iron-laden PACs are recognized as xenosiderophores to cope with iron depletion. Hence, we identified novel signaling mechanisms for iron acquisition and siderophore uptake regulation in A. muciniphila MucT upon exposure to PACs, enhancing our understanding of the role of dietary PACs in selectively promoting this gut symbiont and potentially outcompeting pathogenic bacteria.

BACKGROUND:Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear. METHODS:We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from Akkermansia muciniphila, and their impact on vasculitis development was assessed. RESULTS:We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100 also reduced the severity of vascular inflammation. CONCLUSIONS:This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.

This study investigated the safety and feasibility of daily ingestion of autologous lyophilized fecal microbiota capsules (a-LFMCs) for preserving beta-cell function in individuals with type 1 diabetes (T1D). We evaluated a-LFMC in an open-label, single-arm pilot study (NCT05323162) with 10 individuals with T1D. The study included a 3-month run-in period, 3 months of daily a-LFMC treatment, and a 3-month follow-up. Beta-cell function was assessed using mixed-meal stimulated C-peptide area under the curve (AUC). During the run-in period, beta-cell function significantly declined (mean ΔAUC -12.02 ± 5.09 nmol/L*min, p = 0.025). There was no decrease in beta-cell function during the a-LFMC treatment period (mean ΔAUC 0.76 ± 5.09 nmol/L*min, p = 0.88) and the follow-up period (mean ΔAUC 0.96 ± 5.09 nmol/L*min, p = 0.85). No serious adverse events occurred, though constipation increased during the treatment period (0% vs. 30%, p = 0.021). a-LFMC treatment was found to be safe and potentially contributes to preserving beta-cell function in T1D patients. A larger randomized placebo-controlled trial is needed to confirm these promising findings.

The effect of fermented foods on healthy human gut microbiota structure and function, particularly its seasonal preference and frequent long-term consumption, has been largely uncharacterised. Here, we assess the gut microbiota and metabolite composition of 78 healthy Indian agrarian individuals who differ in the intake of fermented milk and soybean products by seasonal sampling during hot-humid summer, autumn and dry winter. Here we show that, seasonal shifts between the Prevotella- and Bifidobacterium/Ruminococcus-driven community types, or ecological states, and associated fatty acid derivatives, with a bimodal change in Bacteroidota community structure during summer, particularly in fermented milk consumers. Our results associate long-term fermented food consumption with reduced gut microbiota diversity and bacterial load. We identify taxonomic groups that drive the seasonal fluctuation and associated shifts between the two ecological states in gut microbiota. This understanding may pave the way towards developing strategies to sustain a healthy and resilient gut microbiota through dietary interventions.

Aim: This study aims to explore the interplay between host immune factors and gut microbiota in human infants in vivo using time-series daily stool samples and identify biomarkers of host-microbe interactions. Methods: 216 faecal samples collected from infants aged 5-6 or 11-12 months were analysed for gut microbiota composition, total bacterial load, and biomarkers of immune function. Results: We identified indications of microbial stimulation of eosinophil cationic protein (ECP), IgA, calprotectin (Cal), intestinal alkaline phosphatase (IAP), and Bactericidal/permeability-increasing protein (BPI) at 6 and 12 months, as well as stimulation of lipocalin 2 (LCN2), lactoferrin (LTF), and alpha-defensin-5 only at 6 months. The associations between biomarker concentrations and bacterial population growth were primarily positive at 6 months and mostly negative at 12 months, suggesting increasing host regulation of the microbiota with age. The exceptions were IAP, which was predictive of declining bacterial populations at both time points, and Cal, whose associations changed from negative at 6 months to positive at 12 months. Conclusion: There is an age-associated development in the correlation pattern between bacterial population growth and the biomarker concentrations, suggesting that host-microbe interactions change during early development. Albumin appeared as a potential marker of gut permeability, while LCN2 seemed to correlate with gut transit time. Mucin degradation appeared to decrease with age. Mucin2 and IAP emerged as potentially important regulators of the bacterial populations in the infant gut. The study demonstrates the utility of biomarker and bacteria profiling from daily stool samples for analysing in vivo associations between the immune system and the gut microbiota and provides evidence of host regulation of the microbiota in infants.