Central American seminars for young psychiatrists of the region and training of leaders in community mental health. Sweden/PAHO-WHO collaboration program

Human gut Bacteroides and Parabacteroides species play crucial roles in human health and are known for their capacity to utilize diverse polysaccharides. Understanding how these bacteria utilize medicinal polysaccharides is foundational for developing polysaccharides-based prebiotics and drugs. Here, we systematically mapped the utilization profiles of 20 different medicinal polysaccharides by 28 human gut Bacteroides and Parabacteroides species. The growth profiles exhibited substantial variation across different bacterial species and medicinal polysaccharides. Ginseng polysaccharides promoted the growth of multiple Bacteroides and Parabacteroides species; in contrast, Dendrobium polysaccharides selectively promoted the growth of Bacteroides uniformis. This distinct utilization profile was associated with genomic variation in carbohydrate-active enzymes, rather than monosaccharides composition variation among medicinal polysaccharides. Through comparative transcriptomics and genetical manipulation, we validated that the polysaccharide utilization locus PUL34_Bu enabled Bacteroides uniformis to utilize Dendrobium polysaccharides (i.e. glucomannan). In addition, we found that the GH26 enzyme in PUL34_Bu allowed Bacteroides uniformis to utilize multiple plant-derived mannan. Overall, our results revealed the selective utilization of medicinal polysaccharide by Bacteroides and Parabacteroides species and provided insights into the use of polysaccharides in engineering the human gut microbiome.

Cranberry is associated with multiple health benefits, which are mostly attributed to its high content of (poly)phenols, particularly flavan-3-ols. However, clinical trials attempting to demonstrate these positive effects have yielded heterogeneous results, partly due to the high inter-individual variability associated with gut microbiota interaction with these molecules. In fact, several studies have demonstrated the ability of these molecules to modulate the gut microbiota in animal and in vitro models, but there is a scarcity of information in human subjects. In addition, it has been recently reported that cranberry also contains high concentrations of oligosaccharides, which could contribute to its bioactivity. Hence, the aim of this study was to fully characterize the (poly)phenolic and oligosaccharidic contents of a commercially available cranberry extract and evaluate its capacity to positively modulate the gut microbiota of 28 human subjects. After only four days, the (poly)phenols and oligosaccharides-rich cranberry extract, induced a strong bifidogenic effect, along with an increase in the abundance of several butyrate-producing bacteria, such as Clostridium and Anaerobutyricum. Plasmatic and fecal short-chain fatty acids profiles were also altered by the cranberry extract with a decrease in acetate ratio and an increase in butyrate ratio. Finally, to characterize the inter-individual variability, we stratified the participants according to the alterations observed in the fecal microbiota following supplementation. Interestingly, individuals having a microbiota characterized by the presence of Prevotella benefited from an increase in Faecalibacterium with the cranberry extract supplementation.

The gut microbiota (GM) and its potential functions play a crucial role in maintaining host health and longevity. The aim of this study was to investigate the potential relationship between GM and longevity. We collected fecal samples from 92 healthy volunteers (middle-aged and elderly: 43–79 years old; longevity: ≥ 90 years old) from Changshou Town, Zhongxiang City, Hubei, China. In addition, we collected samples from 30 healthy middle-aged and elderly controls (aged 51–70 years) from Wuhan, Hubei. The 16S rDNA V3 + V4 region of the fecal samples was sequenced using high-throughput sequencing technology. Diversity analysis results showed that the elderly group with longevity and the elderly group with low body mass index (BMI) exhibited higher α diversity. However, no significant difference was observed in β diversity. The results of the microbiome composition indicate that Firmicutes, Proteobacteria, and Bacteroidota are the core phyla in all groups. Compared to younger elderly individuals, Akkermansia and Lactobacillus are significantly enriched in the long-lived elderly group, while Megamonas is significantly reduced. In addition, a high abundance of Akkermansia is a significant characteristic of elderly populations with low BMI values. Furthermore, the functional prediction results showed that the elderly longevity group had higher abilities in short-chain fatty acid metabolism, amino acid metabolism, and xenobiotic biodegradation. Taken together, our study provides characteristic information on GM in the long-lived elderly population in Changshou Town. This study can serve as a valuable addition to the current research on age-related GM.Key points• The gut microbiota of elderly individuals with longevity and low BMI exhibit higher alpha diversity• Gut microbiota diversity did not differ significantly between genders in the elderly population• Several potentially beneficial bacteria (e.g., Akkermansia and Lactobacillus) are enriched in long-lived individuals

PurposeTo investigate the causal relationships between gut microbiota and novel adult-onset type 2 diabetes mellitus(T2DM) subtypes.MethodsWe conducted Mendelian randomization (MR) analyses using genome-wide association data from European populations. Initial MR analyses examined associations between gut microbiota and four T2DM subtypes, followed by validation analyses using type 1 diabetes mellitus(T1DM) and T2DM GWAS data. We also performed bidirectional MR analyses and tested for heterogeneity and pleiotropy across all analyses.ResultsOur MR analyses revealed distinctive associations between gut microbiota and T2DM subtypes: six bacterial taxa with severe insulin-deficient diabetes (SIDD), four with severe insulin-resistant diabetes (SIRD), eight with mild obesity-related diabetes (MOD), and eight with mild age-related diabetes (MARD). These associations were distinct from T1DM findings. Six bacterial taxa were validated in T2DM analyses, with four showing directionally consistent effects: Class Clostridia (OR = 0.57, P = 0.045) and Order Clostridiales (OR = 0.57, P = 0.045) were associated with reduced MOD risk, while species Catus (OR = 1.80, P = 0.007) was associated with increased MOD risk, and genus Holdemania (OR = 2.51, P = 0.004) was associated with increased SIRD risk. No significant heterogeneity or pleiotropy was observed across analyses.ConclusionsOur MR analyses reveal novel causal relationships between gut microbiota and adult-onset T2DM subtypes, though further validation studies are warranted.

BackgroundUndernutrition (UN) is a critical public health issue that threatens the lives of children under five in developing countries. While evidence indicates the crucial role of the gut microbiome (GM) in UN pathogenesis, the strain-level inspection and bacterial co-occurrence network investigation in the GM of UN children are lacking.ResultsThis study examines the strain compositions of the GM in 61 undernutrition patients (UN group) and 36 healthy children (HC group) and explores the topological features of GM co-occurrence networks using a complex network strategy. The strain-level annotation reveals that the differentially enriched species between the UN and HC groups are due to discriminated strain compositions. For example, Prevotella copri is mainly composed of P. copri ASM1680343v1 and P. copri ASM345920v1 in the HC group, but it is composed of P. copri ASM346549v1 and P. copri ASM347465v1 in the UN group. In addition, the UN-risk model constructed at the strain level demonstrates higher accuracy (AUC = 0.810) than that at the species level (AUC = 0.743). With complex network analysis, we further discovered that the UN group had a more complex GM co-occurrence network, with more hub bacteria and a higher clustering coefficient but lower information transfer efficiencies. Moreover, the results at the strain level suggested the inaccurate and even false conclusions obtained from species level analysis.ConclusionsOverall, this study highlights the importance of examining the GM at the strain level and investigating bacterial co-occurrence networks to advance our knowledge of UN pathogenesis.

Malaria is caused by Plasmodium species and remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the contribution of specific bacteria to the risk of severe malaria is unknown. Here, multiomics approaches demonstrate that specific species of Bacteroides are causally linked to the risk of severe malaria. Plasmodium yoelii hyperparasitemia-resistant mice gavaged with murine-isolated Bacteroides fragilis develop P. yoelii hyperparasitemia. Moreover, Bacteroides are significantly more abundant in Ugandan children with severe malarial anemia than with asymptomatic P. falciparum infection. Human isolates of Bacteroides caccae, Bacteroides uniformis, and Bacteroides ovatus were able to cause susceptibility to severe malaria in mice. While monocolonization of germ-free mice with Bacteroides alone is insufficient to cause susceptibility to hyperparasitemia, meta-analysis across multiple studies support a main role for Bacteroides in susceptibility to severe malaria. Approaches that target gut Bacteroides present an opportunity to prevent severe malaria and associated deaths.

Abstract The gut microbiome plays a crucial role in human health, but the molecular mechanisms underlying microbial interactions remain poorly understood. Activity-based protein profiling (ABPP) enables functional annotation of uncharacterized enzymes, particularly proteases, using chemical tools. Applying ABPP, Bacteroides fragilis Protease 1 (Bfp1) was identified as an activator of the human protease-activated receptor 2 (PAR2), modulating intestinal inflammation and barrier integrity.

The microbial ecology of Mycobacterium avium subspecies paratuberculosis infections (MAP) within the context of Multiple Sclerosis (MS) is largely an unexplored topic in the literature. Thus, we have characterized the compositional and predicted functional differences of the gut microbiome between MS patients with MAP (MAP+) and without (MAP−) infection. This was done in the context of exposome differences (through self-reported filled questionnaires), principally in anthropometric and sociodemographic patterns to gain an understanding of the gut microbiome dynamics. 16S rRNA microbiome profiling of faecal samples (n = 69) was performed for four groups, which differed by disease and MAP infection: healthy cohort (HC) MAP−; HC MAP+ ; MS MAP−; and MS MAP+ . Using a dynamic strategy, with MAP infection and time of sampling as occupancy models, we have recovered the core microbiome for both HC and MS individuals. Additional application of neutral modeling suggests key genera that are under selection pressure by the hosts. These include members of the phyla Actinobacteriota, Bacteroidota, and Firmicutes. As several subjects provided multiple samples, a Quasi Conditional Association Test that incorporates paired-nature of samples found major differences in Archaea. To consolidate treatment groups, confounders, microbiome, and the disease outcome parameters, a mediation analysis is performed for MS cohort. This highlighted certain genera i.e., Sutterella, Akkermansia, Bacteriodes, Gastranaerophilales, Alistipes, Balutia, Faecalibacterium, Lachnospiraceae, Anaerostipes, Ruminococcaceae, Eggerthellaceae and Clostridia-UCG-014 having mediatory effect using disease duration as an outcome and MAP infection as a treatment group. Our analyses indicate that the gut microbiome may be an important target for dietary and lifestyle intervention in MS patients with and without MAP infection.

The liquid diet composition can affect dairy calves' performance and diarrhea incidence. The effect of three liquid diets on performance, incidence of diarrhea, and microbial community during diarrhea occurrence in dairy calves were evaluated. At birth, 35 dairy calves (20 male and 15 female) were randomly assigned to one of three treatments—refrigerated whole milk (WM), acidified whole milk (AWM), and milk replacer (MR). Intake, fecal score, and rectal temperature were evaluated daily, and performance and blood parameters were evaluated weekly during the preweaning period. Fecal samples from diarrheic calves were collected, and one initial and one final sample for each episode were selected. The bacterial community was assessed by sequencing the V3-V4 region of the 16S rRNA gene on the Illumina MiSeq platform and analyzed using the DADA2 pipeline. Calves fed WM had higher body weight at weaning, average daily gain, body measurements, and concentration of blood metabolites. The AWM-fed calves had a lower rectal temperature and fever days. Moreover, the MR-fed calves had lower beta-hydroxybutyrate concentration and a higher incidence of diarrhea. The fecal bacterial community of diarrheic calves showed dissimilarity among the AWM and the other treatments. At the compositional level, we observed a higher abundance of Fusobacterium and Ruminococcus genera (AWM), Prevotella (WM), and Lactobacillus (MR). In the AWM and MR diarrheic calves' feces, we also observed some beneficial bacterial genera. The performance and incidence of diarrhea of dairy calves were influenced by the liquid diet consumed and the bacterial composition of diarrhea.

The gut microbiome is our lifetime companion, regulating our health from birth throughout the lifespan. The gut microbiome composition changes continually with age, influencing both physiological and immunological development. Emerging evidence highlights the close association, and thus implication, of the microbiome with healthy disease-free aging and longevity. Accordingly, targeting the gut microbiome is emerging as a promising avenue to prevent, alleviate, and ameliorate aging-related disorders. Herein, we provide a prospective and inclusive framework of the close connection of the gut microbiome with human aging, while contemplating how this association is intertwined with age-related diseases. We delve into recently emerging and potential microbiome-based therapeutics that are projected to aid in alleviating myriad aging-related diseases, thereby enhancing the health and well-being of the aging population. Finally, we present a foundation and perspective underlining the prospects of microbiome-based therapeutics developed and tailored precisely for the elderly, with the overarching goal of promoting health and longevity.