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Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32 Gut bacteria influence patient response to cancer therapy. Anti–PD-1–based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients’ microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16 S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum , Collinsella aerofaciens , and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti–PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.

Background Human milk oligosaccharides (HMOs) are one of the major glycan source of the infant gut microbiota. The two species that predominate the infant bifidobacteria community, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, possess an arsenal of enzymes including α-fucosidases, sialidases, and β-galactosidases to metabolise HMOs. Recently bifidobacteria were obtained from the stool of six month old Kenyan infants including species such as Bifidobacterium kashiwanohense, and Bifidobacterium pseudolongum that are not frequently isolated from infant stool. The aim of this study was to characterize HMOs utilization by these isolates. Strains were grown in presence of 2′-fucosyllactose (2′-FL), 3′-fucosyllactose (3′-FL), 3′-sialyl-lactose (3′-SL), 6′-sialyl-lactose (6′-SL), and Lacto-N-neotetraose (LNnT). We further investigated metabolites formed during L-fucose and fucosyllactose utilization, and aimed to identify genes and pathways involved through genome comparison. Results Bifidobacterium longum subsp. infantis isolates , Bifidobacterium longum subsp. suis BSM11-5 and B. kashiwanohense strains grew in the presence of 2′-FL and 3′- FL. All B. longum isolates utilized the L-fucose moiety, while B. kashiwanohense accumulated L-fucose in the supernatant. 1,2-propanediol (1,2-PD) was the major metabolite from L-fucose fermentation, and was formed in equimolar amounts by B. longum isolates. Alpha-fucosidases were detected in all strains that degraded fucosyllactose. B. longum subsp. infantis TPY11-2 harboured four α-fucosidases with 95–99 % similarity to the type strain. B. kashiwanohense DSM 21854 and PV20-2 possessed three and one α-fucosidase, respectively. The two α-fucosidases of B. longum subsp. suis were 78–80 % similar to B. longum subsp. infantis and were highly similar to B. kashiwanohense α-fucosidases (95–99 %). The genomes of B. longum strains that were capable of utilizing L-fucose harboured two gene regions that encoded enzymes predicted to metabolize L-fucose to L-lactaldehyde, the precursor of 1,2-PD, via non-phosphorylated intermediates. Conclusion Here we observed that the ability to utilize fucosyllactose is a trait of various bifidobacteria species. For the first time, strains of B. longum subsp. infantis and an isolate of B. longum subsp. suis were shown to use L-fucose to form 1,2-PD. As 1,2-PD is a precursor for intestinal propionate formation, bifidobacterial L-fucose utilization may impact intestinal short chain fatty acid balance. A L-fucose utilization pathway for bifidobacteria is suggested.

The infant intestinal microbiota is often colonized by two subspecies of Bifidobacterium longum: subsp. infantis (B. infantis) and subsp. longum (B. longum). Competitive growth of B. infantis in the neonate intestine has been linked to the utilization of human milk oligosaccharides (HMO). However, little is known how B. longum consumes HMO. In this study, infant-borne B. longum strains exhibited varying HMO growth phenotypes. While all strains efficiently utilized lacto-N-tetraose, certain strains additionally metabolized fucosylated HMO. B. longum SC596 grew vigorously on HMO, and glycoprofiling revealed a preference for consumption of fucosylated HMO. Transcriptomes of SC596 during early-stage growth on HMO were more similar to growth on fucosyllactose, transiting later to a pattern similar to growth on neutral HMO. B. longum SC596 contains a novel gene cluster devoted to the utilization of fucosylated HMO, including genes for import of fucosylated molecules, fucose metabolism and two α-fucosidases. This cluster showed a modular induction during early growth on HMO and fucosyllactose. This work clarifies the genomic and physiological variation of infant-borne B. longum to HMO consumption, which resembles B. infantis. The capability to preferentially consume fucosylated HMO suggests a competitive advantage for these unique B. longum strains in the breast-fed infant gut.

Microbial communities are often composed by complex mixtures of multiple strains of the same species, characterized by a wide genomic and phenotypic variability. Computational methods able to identify, quantify and classify the different strains present in a sample are essential to fully exploit the potential of metagenomic sequencing in microbial ecology, with applications that range from the epidemiology of infectious diseases to the characterization of the dynamics of microbial colonization. Here we present a computational approach that uses the available genomic data to reconstruct complex strain profiles from metagenomic sequencing, quantifying the abundances of the different strains and cataloging them according to the population structure of the species. We validate the method on synthetic data sets and apply it to the characterization of the strain distribution of several important bacterial species in real samples, showing how its application provides novel insights on the structure and complexity of the microbiota. Microbiota is often a complex mixture of multiple coexisting species and strains with high level of phenotypic and genomic variability. Here, Albanese and Donati develop StrainEst for estimating the number and identity of coexisting strains and their relative abundances in mixed metagenomic samples.

Background The importance of the gut microbiota at the early stage of life and their longitudinal effect on host health have recently been well investigated. In particular, Bifidobacterium longum subsp. longum , a common component of infant gut microbiota, appears in the gut shortly after birth and can be detected there throughout an individual’s lifespan. However, it remains unclear whether this species colonizes in the gut over the long term from early infancy. Here, we investigated the long-term colonization of B . longum subsp. longum by comparing the genotypes of isolates obtained at different time points from individual subjects. Strains were isolated over time from the feces of 12 subjects followed from early infancy (the first six months of life) up to childhood (approximately six years of age). We also considered whether the strains were transmitted from their mothers’ perinatal samples (prenatal feces and postnatal breast milk). Results Intra-species diversity of B. longum subsp. longum was observed in some subjects’ fecal samples collected in early infancy and childhood, as well as in the prenatal fecal samples of their mothers. Among the highlighted strains, several were confirmed to colonize and persist in single individuals from as early as 90 days of age for more than six years; these were classified as long-term colonizers. One of the long-term colonizers was also detected from the corresponding mother’s postnatal breast milk. Quantitative polymerase chain reaction data suggested that these long-term colonizers persisted in the subjects’ gut despite the existence of the other predominant species of Bifidobacterium . Conclusions Our results showed that several strains belonging to B. longum subsp. longum colonized in the human gut from early infancy through more than six years, confirming the existence of long-term colonizers from this period. Moreover, the results suggested that these strains persisted in the subjects’ gut while co-existing with the other predominant bifidobacterial species. Our findings also suggested the importance of microbial-strain colonization in early infancy relative to their succession and showed the possibility that probiotics targeting infants might have longitudinal effects. Trial Registration TRN: ISRCTN25216339 . Date of registration: 11/03/2016. Prospectively registered.

Background Blastocystis is a common gut eukaryote detected in humans and animals. It has been associated with gastrointestinal disease in the past although recent metagenomic studies also suggest that it is a member of normal microbiota. This study investigates interactions between pathogenic human isolates belonging to Blastocystis subtype 7 (ST7) and bacterial representatives of the gut microbiota. Results Generally, Blastocystis ST7 exerts a positive effect on the viability of representative gut bacteria except on Bifidobacterium longum . Gene expression analysis and flow cytometry indicate that the bacterium may be undergoing oxidative stress in the presence of Blastocystis . In vitro assays demonstrate that Blastocystis -induced host responses are able to decrease Bifidobacterium counts. Mice infected with Blastocystis also reveal a decrease in beneficial bacteria Bifidobacterium and Lactobacillus . Conclusions This study shows that particular isolates of Blastocystis ST7 cause changes in microbiota populations and potentially lead to an imbalance of the gut microbiota. This study suggests that certain isolates of Blastocystis exert their pathogenic effects through disruption of the gut microbiota and provides a counterpoint to the increasing reports indicating the commensal nature of this ubiquitous parasite.

The gut microbiota plays a crucial role in gastrointestinal health, immune function, and overall well-being. Dysbiosis has been linked to various conditions such as colon cancer, atopic diseases, mental disorders, autoimmune disorders, obesity, and diabetes. This in vitro study aims to assess the safety and functional potential of two probiotic strains, Lactiplantibacillus (L) plantarum and Bifidobacterium (B) longum , focusing on their anti-lipidemic, anti-diabetic, antioxidant, and probiotic properties. The strains were tested for stress tolerance, including acidic, alkaline, osmotic, oxidative, thermal, detergent, bile salt, and pancreatic enzyme conditions. Both strains exhibited strong resilience, often surpassing the control strain. Their antioxidant activity, measured by radical scavenging ability, was comparable to ascorbic acid, with values of 77% for L. plantarum and 92% for B. longum . Cholesterol-lowering capacity reached 50% and 49% after 3 days, increasing to 59% and 78% after 7 days, respectively. Hydrophobicity, an indicator of adhesion potential, was approximately 78% for L. plantarum and 80% for B. longum . Additionally, both strains showed low α-amylase activity (91.65 and 92.33 U/ml), suggesting a potential role in slowing carbohydrate digestion and managing blood glucose levels. Overall, the strains demonstrated favorable safety profiles and promising functional attributes for alleviating hyperlipidemia and diabetes. PCA and heatmap analyses further highlighted L. plantarum as the most promising candidate. Clinical trial Not applicable.

Bifidobacteria, a genus of obligate anaerobes, comprise a major component of the intestinal microbiota. Importantly, bifidobacteria participate in immune reactions. These bacteria carry a species-specific operon in which the gene encodes a multifunctional protein FN3 that mediates bacterial adhesion to the intestinal epithelium and is capable of binding individual cytokines. Bioinformatics and biochemical approaches were used to study the possible interaction of recombinant ∆FN3 fragments of and strains with cytokines TNF-α, IL-6, IL-8, and IL-10. De novo molecular modeling generated, for the first time, the structural models of species-derived ∆FN3 proteins and revealed new tentative regions for differential cytokine binding. Combined treatment with ∆FN3 and TNF-α induced TNF-α mRNA abundance in the human monocytic cell line. Altogether, these findings provide structural evidence for the regulation of immune reactions by microbiota-derived proteins.

Autism spectrum disorders (ASD) consist of a range of neurodevelopmental conditions accompanied by dysbiosis of gut microbiota. Therefore, a number of microbiota manipulation strategies were developed to restore their balance. However, a comprehensive comparison of the various methods on gut microbiota is still lacking. Here, we evaluated the effect of (BF) treatment and fecal microbiota transplantation (FT) on gut microbiota in a propionic acid (PPA) rat model of autism using 16S rRNA sequencing. Following PPA treatment, gut microbiota showed depletion of Bacteroidia and accompanied by a concomitant increase of , , and . The dysbiosis was predicted to cause increased levels of porphyrin metabolism and impairments of acyl-CoA thioesterase and ubiquinone biosynthesis. On the contrary, BF and FT treatments resulted in a distinct increase of , , , , and . The taxa in BF group positively correlated with vitamin B12 and flagella biosynthesis, while FT mainly enriched flagella biosynthesis. In contrast, BF and FT treatments negatively correlated with succinate biosynthesis, pyruvate metabolism, nitrogen metabolism, beta-Lactam resistance, and peptidoglycan biosynthesis. Therefore, the present study demonstrated that BF and FT treatments restored the PPA-induced dysbiosis in a treatment-specific manner.

The metabolic processes of Bifidobacterium longum subsp. infantis, an early coloniser of the human gut, are essential for gut health, mainly due to the production of indole derivatives from tryptophan. This study investigates the capacity of B. infantis ATCC 15697 to biosynthesise indole‐3‐lactate (ILA), indole‐3‐acetate (IAA), and indole‐3‐carboxaldehyde (I3CA) and the regulatory effects of substrate availability on these pathways. The tryptophan catabolic profile of B. infantis ATCC 15697 under a non‐growing but metabolically active state was investigated. Through HPLC‐PDA and LC–MS analyses, we confirmed for the first time the production of IAA and I3CA by B. infantis ATCC 15697. The results revealed a dose‐dependent relationship between tryptophan availability and the production of indole derivatives, highlighting the nutrient‐driven effect of these metabolic pathways. By integrating genomic analysis with metabolic profiles, we proposed potential pathways underlying the biosynthesis of IAA and I3CA from tryptophan. These findings enhance our understanding of the role of B. infantis ATCC 15697 in human health, with ILA, IAA, and I3CA contributing to immune modulation and gut health. We also provide a platform for using B. infantis ATCC 15697 as a biocatalyst for the biosynthesis of beneficial indole derivatives through whole‐cell bioconversion, which was further demonstrated in B. infantis ATCC 25962 and ATCC 15702. Future in vivo studies will help clarify the impact of these metabolites on the gut environment and inform dietary and probiotic strategies for enhancing indole derivatives production. Bifidobacterium longum subsp. infantis converts tryptophan into indole‐3‐lactate, indole‐3‐acetate and indole‐3‐carboxaldehyde. Production is substrate‐dependent, with higher tryptophan levels enhancing yields. This study reveals metabolic modulation in nutrient‐rich and resting states, emphasising B. infantis' role in producing beneficial indole derivatives for gut health.