Characterizations of multi-kingdom gut microbiota in immune checkpoint inhibitor-treated hepatocellular carcinoma.

BACKGROUND: The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood. METHODS: From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC. RESULTS: Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6-8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria (Actinomyces_sp_ICM47, and Senegalimassilia_anaerobia) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI. CONCLUSIONS: In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers.

Rhizosphere Microbial Response to Multiple Metal(loid)s in Different Contaminated Arable Soils Indicates Crop-Specific Metal-Microbe Interactions.

In this study, we sampled rhizosphere soils from seven different agricultural fields adjacent to mining areas and cultivated with different crops (corn, rice, or soybean), to study the interactions among the innate microbiota, soil chemical properties, plants, and metal contamination. The rhizosphere bacterial communities were characterized by Illumina sequencing of the 16S rRNA genes, and their interactions with the local environments, including biotic and abiotic factors, were analyzed. Overall, these soils were heavily contaminated with multiple metal(loid)s, including V, Cr, Cu, Sb, Pb, Cd, and As. The interactions between environmental parameters and microbial communities were identified using multivariate regression tree analysis, canonical correspondence analysis, and network analysis. Notably, metal-microbe interactions were observed to be crop specific. The rhizosphere communities were strongly correlated with V and Cr levels, although these sites were contaminated from Sb and Zn/Pb mining, suggesting that these two less-addressed metals may play important roles in shaping the rhizosphere microbiota. Members of Gaiellaceae cooccurred with other bacterial taxa (biotic interactions) and several metal(loid)s, suggesting potential metal(loid) resistance or cycling involving this less-well-known taxon.IMPORTANCE The rhizosphere is the "hub" for plant-microbe interactions and an active region for exchange of nutrients and energy between soil and plants. In arable soils contaminated by mining activities, the rhizosphere may be an important barrier resisting metal uptake. Therefore, the responses of the rhizosphere microbiota to metal contamination involve important biogeochemical processes, which can affect metal bioavailability and thus impact food safety. However, understanding these processes remains a challenge. The current study illustrates that metal-microbe interactions may be crop specific and some less-addressed metals, such as V and Cr, may play important roles in shaping bacterial communities. The current study provides new insights into metal-microbe interactions and contributes to future implementation and monitoring efforts in contaminated arable soils.

Paddy soil microbial communities driven by environment- and microbe-microbe interactions: A case study of elevation-resolved microbial communities in a rice terrace.

Rice paddies are a significant source of the greenhouse gas methane, which mainly originates from microbial activity. Methane generation in anaerobic systems involves complex interactions of multiple functional microbial groups. Rice paddies installed in hilly terrain are often terraced, providing multiple quasi-independent plots differing primarily in their elevation up a hillside. This represents an excellent study site to explore the influence of environmental factors on microbial communities and interactions among microbial populations. In this study, we used a combination of geochemical analyses, high-throughput amplicon sequencing, and statistical methods to elucidate these interactions. Sulfate, total nitrogen, total iron, and total organic carbon were determined to be critical factors in steering the ecosystem composition and function. Sulfate-reducing bacteria predominated in the rice terrace microbial communities, and Fe(III)-reducing and methane-oxidizing bacteria were abundant as well. Biotic interactions indicated by co-occurrence network analysis suggest mutualistic interactions among these three functional groups. Paddy-scale methane production may be affected by competition among methanogens and sulfate- and Fe(III)-reducing bacteria, or by direct methane oxidation by methane-oxidizing bacteria. CAPSULE: Microbial communities were characterized in rice terrace. The environment- and microbe-microbe interactions indicated the mitigation of sulfate and Fe on methane production.