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Tibetan kefir grains (TKGs) are a complex protein-lipid-polysaccharide matrix composed of various microorganisms. Microorganisms have the benefit of being effective, secure, and controllable when used for selenium enrichment. In this study, selenium-enriched Tibetan kefir grains (Se-TKGs) were made, and the microbiology composition was analyzed through a metagenomic analysis, to explore the influence of selenium enrichment. The microbial composition of TKGs and Se-TKGs, as well as the probiotic species, quorum sensing system (QS) and functional genes were compared and evaluated. Lactobacillus kefiranofaciens was the most abundant microbial species in both communities. Compared with TKGs, Se-TKGs had a much higher relative abundance of acetic acid bacteria. Lactobacillus helveticus was the most common probiotic species both in TKGs and Se-TKGs. Probiotics with antibacterial and anti-inflammatory properties were more abundant in Se-TKGs. QS analysis revealed that Se-TKGs contained more QS system-associated genes than TKGs. Moreover, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the pathway for human disease ko01501 had the greatest relative abundance in both TKGs and Se-TKGs. Compared with TKGs, Se-TKGs demonstrated a greater relative abundance of different drug resistance-related metabolic pathways. Additionally, linear discriminant analysis effect size was used to examine the biomarkers responsible for the difference between the two groups. In this study, we focused on the microbiological structure of TKGs and Se-TKGs, with the aim of establishing a foundation for a more thorough investigation of Se-TKGs and providing a basis for exploring potential future use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors report no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tibetan kefir (TK) is a good source of probiotics and has antioxidative, anti-inflammatory, and gut microbiota-regulating properties. Ochratoxin A (OTA) causes liver injury through the gut microbiota. It is unclear whether TK has differential effects on the gut-liver axis and whether these effects can alleviate liver injury induced by OTA. Herein, we investigated the hepatoprotective effect of TK in OTA-fed mice and its underlying mechanisms in the context of the gut. The results indicate that microorganisms in TK bound to OTA and decreased its gastrointestinal absorption. TK improved the intestinal barriers, and suppressed oxidative stress and inflammatory responses. Moreover, TK supplementation alleviated the gut microbiota dysbiosis by enriching beneficial microbiota such as Akkermansia and Lachnospiraceae UCG-006 , and reducing harmful bacteria. Importantly, TK supplementation reversed the liver injury by reducing gut leakage of Bacteroides and lipopolysaccharides. Furthermore, untargeted metabolomics revealed that TK reversed the perturbation of metabolites involved in glycerophospholipid and bile acid metabolism, and regulated metabolites that are pertinent to the citrate cycle and tryptophan metabolism. TK also increased the production of short-chain fatty acids and anti-inflammatory metabolites. These data are consistent with the protective effects of TK against OTA-induced liver injury by maintaining the intestinal barrier and modulating the gut microbiota and metabolites. These findings will facilitate therapeutic interventions for mycotoxicosis.

Ochratoxin A (OTA) is reported to cause intestinal damage following ingestion of contaminated foods. Tibetan kefir (TK) is a fermented dairy product that possesses antioxidant, anti-inflammatory, and gut microbiota-regulating properties. However, it is not clear if TK can alleviate OTA-associated intestinal toxicity. Here, we investigated whether TK can prevent OTA-induced intestinal barrier disruption in mice. To this end, OTA-fed mice were treated with sterile water (control) or TK by oral gavage once daily, for 3 weeks. The histological changes of ceca, the expression of tight junction proteins and mucins, and the levels of oxidative stress, inflammatory response, and gut microbiota were then assessed. Results revealed that treatment with TK reversed OTA-driven histopathological changes in the ceca, and was associated with increased cecal mucin levels. TK administration to OTA-treated mice significantly elevated the expression levels of tight junction proteins (claudin-1, zonula occludens-1, and occludin). Additionally, TK supplementation suppressed OTA-induced oxidative stress and reduced inflammation via the NF-κB signaling pathway in the ceca. Moreover, TK supplementation depleted harmful bacteria (e.g., Turicibacter and Desulfovibrio), while supporting short-chain fatty acids (SCFAs)-producing bacteria (e.g., Lachnospiraceae, Blautia, and Ruminococcus), which maintained the SCFAs levels. Taken together, our findings indicate that TK may emerge as a viable dietary strategy to prevent intestinal toxicity-based injuries., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the alleviative effects of Lactobacillus kefiranofaciens JKSP109 (LK) and Saccharomyces cerevisiae JKSP39 (SC) isolated from Tibetan kefir grain on colon inflammation and colorectal carcinogenesis. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to establish a mouse model of colorectal cancer (CRC). The treatment group mice were administered with LK, SC, or the combination of LK and SC for five days per week from the day of receiving AOM. The composition of the gut microbiota was assessed using internal transcribed spacer 2 and 16S rRNA gene high-throughput sequencing. Furthermore, the biomarkers associated with gut barrier integrity, inflammation, regulators of cell proliferation, and apoptosis were evaluated. The results showed that the administration of LK, SC, and their combination increased the body weights and decreased the disease activity index (DAI) score and tumor multiplicity. As compared to the CRC model group, the three treatment groups positively regulated the gut microbiota. Meanwhile, the three treatments also enhanced the gut barrier, decreased the expression of proinflammatory cytokines and oncocyte proliferation indicators, and increased the expression of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive tumor epithelial cells and content of short chain fatty acids in fecal samples. All these results indicated that the LK and SC alleviated the inflammation and colorectal carcinogenesis in AOM/DSS-induced CRC mouse models, and the majority of tested indexes in the combination group were superior to single strain groups.

Tibetan kefir grains (TKGs) are distinctive and complex mixtures with protein-lipid-polysaccharide matrices and multiple microorganism species. The objective of this study was to evaluate the microflora composition, probiotic species and functional genes within TKGs. Metagenomic analysis was used to evaluate communities of three TKGs, revealing the presence of 715 species, with Lactobacillus kefiranofaciens as the most dominant species. The relative abundances of acetic acid bacteria and yeast significantly differed among the three TKGs (acetic acid bacteria: p < 0.01; yeast: p < 0.05), and the dominant yeast species also varied across three TKGs. Lactobacillus helveticus was the most abundant listed probiotic species, and its abundance did not significantly differ across three TKGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that ko01501 was the most abundant pathway that related to human disease. There are 16 different KOs (KEGG Orthology) in the ko01501 pathway were annotated in TKGs, which helps to resist β-lactam. This study provided a new insight into the microbial community structures and the presence of probiotic species within TKGs and provides a foundation for further targeted studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study aimed to confirm the effects of Tibet kefir milk (TKM) on gut microbiota and metabolism. An obesity model was established by feeding a high-fat diet (HFD) to human-microbiota-associated rats. Next-generation sequencing and ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry were applied for gut microbiota and untargeted metabolomics, respectively. After 8 weeks of feeding, the enterotype in the HFD group was switched from ET1 ( Prevotella / Akkermansia -dominant) to ET2 ( Bacteroides / Akkermansia -dominant). Branched-chain amino-acids- and aromatic amino-acids-metabolism increased, and taurine-conjugated bile acids decreased in the HFD group. Compared with the HFD group, taurocholic acid increased in the TKM1 group, while l-threonine decreased, and equol, taurochenodeoxycholate, and taurodeoxycholic acid increased in the TKM2 group. The metabolite alteration suggested restorative bile acid metabolism, modified metabolic pattern of amino acids, and elevation of anti-obesity factors in the TKM-intervened animals. It can be deduced that changes by TKM intervention in the host gut metabolites are the major contributors to reducing fat deposition.

The role of Tibet kefir milk (TKM) feeding on fat deposition was investigated in high-fat diet (HFD)-fed human flora-associated (HFA) rats. TKM feeding reduced abdominal fat mass from 33.9 g to 24.0 g and serum triglyceride (TG) from 0.75 mmol/L to 0.47 mmol/L, and caused lipoprotein lipase (LPL) to decrease from 395.8 ± 36.0 ng/L to 362.3 ± 64.4 ng/L in fat and increase from 287.3 ± 40.8 ng/L to 329.8 ± 48.5 ng/L and 312.5 ± 22.0 to 375.1 ± 30.8 ng/L in liver and serum, respectively. Likewise, TMK feeding down-regulated Lpl gene expression in fat and Angptl4 (angiopoietin-like protein-4, also known as fasting-induced adipose factor) gene expression in liver, and up-regulated Angptl4 gene expression in fat. Sequence analysis showed that the Firmicutes/Bacteroidetes proportion and Verrucomicrobia at the phylum level, Akkermansia, Escherichia and Oscillospira at the genus level, as well as Escherichia coli at the species level were positively regulated by TKM. The results indicated that TKM decreased abdominal fat deposition and serum TG by regulating Lpl and Angptl4 at the transcriptional level. The microbiota groups mentioned above were regulated by TKM at the same time and may be the potential intervention targets to reduce fat deposition., (Copyright © 2019 Elsevier Ltd. All rights reserved.)