Potential novel biomarkers in small intestine for obesity/obesity resistance revealed by multi-omics analysis

Abstract

Background Although obesity is caused by different factors, individual susceptibility to obesity differs among people under the same circumstances. The microbiota in the caecum or fresh faeces and metabolites in blood or urine contribute to obesity resistance; however, the microbiota or metabolites in the small intestine have not been extensively studied. Methods To investigate the relationship between the microbiota or metabolites in the small intestine and susceptibility to obesity, eighty-eight male C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks to establish two models of obesity and obesity resistance. For further study, six mice were chosen from among the obesity models, and twelve mice were randomly chosen from among the obesity resistance models. After fasting plasma glucose and behavioural testing, the mice were fed in single cages for another 4 weeks to observe their weight and food intake. All mice were sacrificed at 20 weeks of age. Serum ALT, AST, HDL, LDL, TG and TC levels were measured using an automatic biochemical analyser. The microbiota and metabolites in the small intestine contents were analysed using 16 S sequencing and an ultrahigh-performance liquid chromatographic system, respectively. Transcripts in the jejunum were evaluated using full-length transcriptome sequencing and verified by qPCR. Results The results showed that HFD induced depression and anxiety behaviours and higher fasting plasma glucose, ALT, AST, HDL, LDL, TG and TC levels in the obese mice; however, these levels were improved in obese resistance mice. The correlation analysis showed that the phosphatidylcholine, TG, and phosphatidylethanolamine levels were higher in obese mice and correlated positively with intestinal microflora (Desulfovibrio and Gemella) and the Cxcl10 gene. A higher abundance of Clostridium_sensu_stricto_1 in obesity-resistant mice correlated negatively with the metabolite contents (neuromedin N and enkephalin L) and Pck1 gene expression and correlated positively with certain metabolites (5-hydroxy-L-tryptophan, cinnamyl alcohol and 1 H-indole-3-acetamide) and genes expression (Gdf15, Igfbp6 and Spp1). Conclusion Clostridium_sensu_stricto_1, neuromedin N, enkephalin L, Pck1, 5-hydroxy-L-tryptophan, Cxcl10 and cinnamyl alcohol may be novel biomarkers in the small intestine for obesity/obesity resistance. These might be helpful for obesity prevention or for treating obese patients.

Medium-chain inulin alleviates the obesity and improves systemic health in diet-induced obese mice via mediating the gut microbiome and metabolome

“…Thus, they form a core functional subset that is associated with BW change and might be a potential regulatory target for the treatment of obesity. In a similar study, Pang et al ( 2022) also reported that Clostridium_sensu_stricto_1 is a biomarker in the gut microbiota for obesity resistance [54]. A high-ber diet selectively promotes the growth of SCFA-producing microbes [2,58], which was consistent with the current ndings.…”

“…In this experiment, inulin mainly enhanced the generation of 5-hydroxy-ltryptophan (5-HTP), which is a precursor substance of serotonin that regulates a series of metabolic and psychological functions, in the metabolism of tryptophan [53]. In a previous study, 5-HTP was linked to weight loss by suppressing appetite [54], but this result is controversial. The bene ts of 5-HTP have mainly been shown to be anti-depressive by many studies [55].…”

Role of microbiota-gut-brain axis in natural aging-related alterations in behavior

“…In addition, aging induced the upregulation of LPS-producing bacterial such as Bacteroidaceae and Bacteroides , which are at lower abundance in young mice. It has been demonstrated that a high abundance of Alistipes , Bacteroides , Clostridium_sensu_stricto _1, Colidextribacter and Lachnoclostridium was associated with dysbiosis, oxidative stress, obesity, chronic inflammation and neurodegenerative diseases, indicating that these microbes may increase the risk of the onset of chronic diseases and inflammation ( Zafar and Saier, 2021 ; Cai et al, 2022 ; Pang et al, 2022 ; Liu et al, 2023 ; Yang et al, 2023 ).…”

Effect of vitamin D3 on lipid droplet growth in adipocytes of mice with HFD‐induced obesity

“…Nantong, Jiangsu, China). After 10 weeks, normal diet mice were continued to be fed after excluding the weight extremes (n = 14), and high-fat diet mice with a body weight (single mouse) of 20% (Buettner et al, 2007;Guo et al, 2020;Pang et al, 2022) or more of the mean body weight of CON group were selected for further studies. Compositions of the normal diet and high-fat diet are listed in Table 1.…”