Accumulating studies have demonstrated that there were intimate correlations between type 2 diabetes mellitus (T2DM) and gut microbiota. By modulating the structure of gut microbiota, a specially designed high-fiber diet was proved to be able to provide obvious beneficial effects for patients with T2DM (Zhao et al., 2018). In fact, the modulation of gut microbiota could not only increase the relative abundances of Lactobacillus, Bifidobacterium and other beneficial microbes, and could also improve the plasma and the fecal bile acid metabolism of patients with T2DM (Gu et al., 2017). Metagenome-wide association study in a cohort of young Chinese individuals identified an obesity-associated gut microbial species (Bacteroides thetaiotaomicron), which could alleviate diet-induced body-weight gain and adiposity by reducing plasma glutamate concentrations (Liu et al., 2017). These findings indicated that the intestinal microbiota might play a critical role in treating obesity and T2DM. Several genera of beneficial bacteria (such as Allobaculum, Bacteroides, Blautia, Butyricoccus, and Phascolarctobacterium) with short-chain fatty acid (SCFA)-producing properties were proved to be associated with the prevention of obesity and insulin resistance in high-fat diet (HFD) fed rats (Zhang et al., 2012; Zhang et al., 2015). A large structural survey of fecal microbiota in 314 healthy Chinese young adults revealed that nine genera of bacteria (including Phascolarctobacterium, Roseburia, Blautia, Faecalibacterium, Clostridium, Subdoligranulum, Ruminococcus, Coprococcus and Bacteroides) with SCFA-producing properties were certified to be necessary for maintaining the host’s health (Zhang et al., 2015). Therefore, many novel strategies (such as prebiotic, probiotic and fecal microbiota transplantation) targeting the gut microbiota could be developed for type 2 diabetes interventions.

The clinical symptoms of anxiety and depression were often observed in patients with T2DM, and the reason might lie in that the diabetic nutrient restrictions and the imbalanced gut microbiota influence the patient’s emotional state (Collins et al., 2009; Semenkovich et al., 2015). The gut microbiota could influence the host’s central neurochemistry and change their stress responses and cognitive behaviors, and the communications between the gut and brain might be related to the various kinds of microbial metabolites, including catecholamines, serotonin, gamma-aminobutyric acid, and SCFAs (Ho & Ross, 2017). In particular, administration of SCFAs were proved to be able to alleviate the stress-induced responsiveness as well as the intestinal permeability, and could also influence the brain immune homeostasis, energy metabolism, and physiological states (Wouw et al., 2018; Valles-Colomer et al., 2019). Moreover, functional food consumption could obviously decrease the autoreactive T cell numbers in lymphoid tissues and decrease the serum concentrations of inflammatory cytokines (Marino et al., 2017). Therefore, the bidirectional communications between the gut and brain could be influenced by nutritional interventions.

Nowadays, personalized nutritional interventions based on transcriptomics, proteomics, and metabolomics techniques could provide additional benefits for patients with T2DM. Consumptions of functional foods and bioactive ingredients could enhance the anti-oxidant properties, the anti-inflammatory activities, the anti-cholesterol activities, and the insulin sensitivity of patients with T2DM (Alkhatib et al., 2017; Zhang and Gregg, 2017; Laksir et al., 2018). The gut microbiota could transduce the nutrients signals and retard the development of chronic inflammation and metabolic disorders, and the administration of functional foods could also increase the abundances of Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella (Shanahan et al., 2017). When the food components of dietary fiber, polyphenols, flavonoids, sterols, and unsaturated fatty acids were digested by the gut microbes, various kinds of microbial metabolites were produced to treat the obesity, non-alcoholic fatty liver disease (NAFLD), and T2DM (Lyu et al., 2017). By regulating the homeostasis of innate and adaptive immune system, the diverse microbiota-derived bioactive molecules could regulate the health and disease of the host (Blander et al., 2017). Recent studies had also proved that the symbiotic bacteria could influence the development and function of the nervous system, which were related to anxiety, depression, and other mental diseases (Sharon et al., 2016). In fact, most of the neurotransmitters in the brain (such as 5-hydroxytryptamine and γ-aminobutyric acid) were produced by the gut microbes, therefore the microbiome-gut-grain axis had a critical impact on stress responses, depression and anxiety (Dinan and Cryan, 2017). Thus, manipulation of functional foods towards the gut microbiota could be applied to fight against the metabolic syndromes and the central nervous system diseases (Barratt et al., 2017; Maier and al'Absi, 2017).

In this study, the profiles of fecal microbiota samples from patients with T2DM altered by a high-fiber diet were studied, and the relations between the microbial communities and the host’s clinical features were also determined and analyzed.

Previous studies had already proved that the gut microbiota was a critical environmental factor for treating T2DM and other metabolic disorders (Liu et al., 2017; C. Zhang et al., 2010). A nutritional diet composed of a high amount of dietary fibers could provide enough carbohydrates for the gut microbiota to ferment, and the microbial metabolites could provide energy supply and regulate the immune function of the host (Justin et al., 2017; Gowd et al., 2019). For example, the SCFAs produced by gut microbiota demonstrated obvious T2DM-alleviating effects (Dalile et al., 2019). In this study, a specially designed high-fiber diet was applied to regulate the composition of intestinal flora in patients with T2DM.

Zhao et al. had revealed that the gut microbiota could bring additional health benefits for patients with T2DM through carbohydrate fermentation and SCFA production (Zhao et al., 2018). Consistent with the previous study, our experiment results also proved that the high-fiber diet could improve the glucose homeostasis of participants with T2DM. When compared with the control group, the serum levels of HbA1c levels and FBG decreased significantly in the treatment group, while the serum levels of insulin and C-peptides increased significantly in the treatment group ( Figure 1 ). Simultaneously, the serum lipid profiles were also improved by the high-fiber diet. The decreased the serum levels of the TC, TG and LDL-C and the increased serum levels of HDL-C in the treatment group indicated the lipid metabolism of participants with T2DM was improved after consumption of a high-fiber diet ( Table 2 ). Therefore, the dietary source of fibers demonstrated obvious protective impacts on glucose homeostasis and lipid metabolism of the patients with T2DM.

Manipulation of the gut microbiota by prebiotic administration could improve the glucose and lipid metabolism in obese and diabetic mice, and the low-grade inflammation were also decreased (Everard et al., 2011). Cani et al. demonstrated that prebiotic-treated ob/ob mice exhibited a lower level of plasma lipopolysaccharide (LPS) and inflammatory cytokines, and the decreased inflammatory tone was proved to be associated with a lower intestinal permeability and an improved tight-junction integrity when compared to controls (Cani et al., 2009). Further analysis indicated that the inulin-supplemented diet could restore the leptin related pathways (especially AMPK signaling pathway) of ob/ob mice, which was mediated by gut microbiota changes (Song et al., 2019). In the current study, the serum levels of inflammatory chemokines (IL-1β, IL-6, MCP-1 and TNF-α) in the treatment group were significantly decreased when compared with the control group ( Figure 2 ). The changes in systematic inflammation might be related to the immune regulatory functions of fermented products of carbohydrates.

The hippocampal neuronal apoptosis and synaptic structural damage were proved to be associated with the overexpression of proinflammatory cytokines and overactivation of microglia and astrocytes, therefore alterations of intestinal flora could inhibit the immune-inflammatory response and signaling by producing SCFAs (Shao et al., 2023). In this research, evaluations of the depression and anxiety symptoms by HAMA and HAMD questionnaires indicated that the depression and anxiety symptoms were improved in the treatment group ( Figure 3 ). Therefore, the improvements in emotional moods were observed when more diverse carbohydrates were consumed and the gut microbiota was altered.

The microbial communities of patients with T2DM were obviously changed after the high-fiber diet administration. The richness and diversity of the bacterial community in the treatment group were both enhanced ( Figure 4 ). The phylum of Firmicutes and Bacteroidota contributed 79.96% proportion of the gut microbes ( Figure 5A ). Compared with the control group, the composition of Firmicutes increased and the composition of Bacteroidota decreased in the treatment group. Therefore, the decreased ratio of F/B value revealed that the gut microbiota in the treatment group changed obviously at the phylum level. The dysbiotic expansion of anaerobic proteobacteria was considered to have an intimate relation with colonic epithelial oxygenation and intestinal inflammation. When compared with the control group, the composition of proteobacteria decreased obviously in the treatment group. As shown in Figures 5B , 6 , several genra of beneficial microbes with lactic acid and SCFAs producing activity were increased after the high-fiber diet intervention, including Lactobacillus(0.08% vs. 4.84%), Akkermansia (0.07% vs. 2.74%), Bifidobacterium (3.70% vs. 5.43%), Bacteroides (12.52% vs. 16.67%), Ruminococcus (1.25% vs. 2.88%), and Blautia(1.56% vs. 1.87%). At the same time, the proportions of Erysipelatoclostridium (1.02% vs. 0.09%), Megamonas (3.96% vs. 2.43%), Prevotella (4.04% vs. 2.40%), Klebsiella (0.65% vs. 0.25%), Desulfovibrio (0.17% vs. 0.07%), and other opportunistic pathogens were decreased in the treatment group. Therefore, the optimized gut microbiota composition could help the host to modulate immune homeostasis and protect gut barrier function. Moreover, the predicted PICRUSt functions demonstrated that pathways related to the carbohydrate and energy metabolism were influenced by the high-fiber diet ( Figure 7 ).

In the present study, clinical data indicated that the increased availability of fermentable carbohydrates was sufficient to induce metabolic improvements in patients with T2DM. The dietary source of fibers demonstrated protective impacts on the gut ecosystem, and the alteration of the gut microbiota composition improved the glucose homeostasis in patients with T2DM.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, PRJNA630022.

The studies involving human participants were reviewed and approved by Ethics Committee of Shanghai Jiao Tong University School of Medicine. The patients/participants provided their written informed consent to participate in this study.

Investigation, LC and LR; software, BoL; methodology, HD, CF, CQ, BiL, and RZ; writing—original draft preparation, ZL; review and editing, HL; supervision, ZM. All authors contributed to the article and approved the submitted version.