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      Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases

      , , , , , ,
      Clinical Nutrition
      Elsevier BV

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          Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

          Immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizeable minority of cancer patients. Here, we show that primary resistance to ICI can be due to abnormal gut microbiome composition. Antibiotics (ATB) inhibited the clinical benefit of ICI in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICI (but not from non-responding patients) into germ-free or ATB-treated mice ameliorated the antitumor effects of PD-1 blockade. Metagenomics of patient stools at diagnosis revealed correlations between clinical responses to ICI and the relative abundance of Akkermansia muciniphila. Oral supplementation with A. muciniphila post-FMT with non-responder feces restored the efficacy of PD-1 blockade in an IL-12-dependent manner, by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into tumor beds.
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            A metagenome-wide association study of gut microbiota in type 2 diabetes.

            Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
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              Enterotypes of the human gut microbiome.

              Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
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                Author and article information

                Contributors
                Journal
                Clinical Nutrition
                Clinical Nutrition
                Elsevier BV
                02615614
                October 2022
                October 2022
                : 41
                : 10
                : 2333-2344
                Article
                10.1016/j.clnu.2022.08.029
                36113229
                e6e760a1-93cc-4561-8fff-10612833c000
                © 2022

                https://www.elsevier.com/tdm/userlicense/1.0/

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