Gut microbiota contains highly diverse microorganisms, which have metabolic, immune, and protective functions and play a vital role in gut homeostasis, and host health (Goldsmith and Sartor, 2014). Fecal microbiota transplantation (FMT) is used to restore the healthy status of the dysbiosis microbiome via introducing the healthy microbiota to the gut. Functioning similarly to probiotics, FMT helps to maintain the microbiotal balance and function. From a microbiological perspective, FMT success can also be defined by a shift in the gut microbiome profile of an individual toward that of the donor (Wilson et al., 2019). Given the implementation of FMT programs, donor selection is a fundamental challenge (Bibbò et al., 2020) and is a crucial component in FMT success (Moayyedi et al., 2015; Vermeire et al., 2016).

Numerous studies have revealed that diet plays an important role in mediating the composition and metabolic function of gut microbiota (Sonnenburg and Bäckhed, 2016). Consumption of dietary fiber interacts directly with gut microbes and leads to the production of key metabolites such as short-chain fatty acids (SCFAs), thus impacting gut microbial ecology, host physiology, and health (Makki et al., 2018; Chang et al., 2021). An industrialized diet consisting of highly refined foods and low in dietary fiber usually induces the dysfunctional intestinal barrier and chronic diseases (Martínez et al., 2015; Yeagle, 2015; García-Montero et al., 2021). When industrialized and non-industrialized populations were compared, the significant differences within the gut microbiota composition was observed, suggesting that bacterial can be driven by differences in diet, including dietary fiber (De Filippo et al., 2010). Mechanistic studies and clinical trials on isolated and extracted fibers have demonstrated promising regulatory effects on the gut microbiota (Gill et al., 2021).

Pig is one of the earliest domesticated livestock species and received an “industrialized” diet in modern feedlots. Thus, supplementation of dietary fiber can be a beneficial modulation of the gut microbiome and has high impactions on humans and livestock that sustain societal needs (Slavin, 2013; Michalak et al., 2020). Previous studies have implicated the supplementation of dietary as a potential feeding strategy to control gut dysfunction by decreasing the retention time of digesta and reducing the proliferation of pathogens in the gut of domestic pigs (Kim et al., 2012; Heo et al., 2013). Unlike other domesticated animals, wild ancestors of domesticated pigs still exist in large numbers in the wild environment (Vigne, 2011). Wild pig mainly feeds on acorns, wild fruits, grassroots, and stems, so the diet of wild boar may have higher cellulose content and lower carbohydrate or fat content (Rivero et al., 2019). When the gut microbiota of specific-pathogen-free pigs, domestic pigs, and wild pigs was compared, specific operational taxonomic units (OTUs) enriched in the gut of wild pigs might contribute to higher resistance to African swine fever than those susceptible animals (Correa-Fiz et al., 2019).

The study of pigs has excellent potential to inform humans due to the many similarities identified in the physiological attributes of these two species. It has been shown that humans share more similarities with pigs in anatomy, genetics, physiology, pharmaceutical bioavailability, and nutrient digestibility than with rodents (Wang et al., 2016). Hence, the pig is a superior model to rodents for studying human physiology and pathology on enteric health. In this study, FMT was used to establish mouse models of gut microbiota in wild and domestic pigs after indigenous microbiota was depleted by antibiotics. The mice were provided with a high-fiber diet and a low-fiber diet to evaluate the effect of FMT and dietary fiber intervention on the gut microbiota, which will help better understand the utilization of both FMT and diet intervention on gut microbiota.

Mice were transplanted with domestic or wild pig fecal microbiota and supplied the diet with differential dietary fiber. After that, gut contents were sampled and sequenced for the detection of bacterial composition in mice. The rarefaction curve of alpha diversity revealed enough observations, and sampling depth has been made in all samples.

There was no significant difference in alpha diversity index in the gut microbiota between the DF and the D group, whereas the Chao 1 index and observed species of gut microbiota in WF mice were significantly lower than that of the W mice. Differential alpha diversity index of gut microbiota in mice transported from the same donor was observed, suggesting that the gut microbiota composition can be shaped by differential dietary fiber (Makki et al., 2018). However, although the diet could shape the gut microbiota patterns, the gut microbiota composition of mice transported from differential donors also showed differential responses to the same diet. For instance, no significant differences in alpha diversity were observed between D and W mice, whereas significant differences in alpha diversity of DF and WF mice were observed. Although FMT has been applied as an effective therapy for the improvement of host health (Kelly et al., 2014; Chinna Meyyappan et al., 2020), contrasting experimental results on FMT were usually observed and challenging to interpret (Vendrik et al., 2020). Our results showed that the diet could be one of the reasons influencing the effectiveness of FMT. Thus, implementing of microbiome-targeted diet might be an essential strategy for the subsequent FMT to sustain the bacterial patterns in the gut (Zhang et al., 2019). The results suggested that both the FMT and diet intervention could influence the gut microbiota composition in mice.

Although mice received treatments and showed differential patterns of gut microbiota, nine specific bacteria OTUs were still observed existing in all samples, including unclassified_f_Porhyromonadaceae, unclassified_f_Lachnospiraceae, Barnesiella, Parabacteroides, Lactobacillus, Bacteroides, and Alistipes. As Bacteroidetes and Firmicutes were the dominant phyla in the gut, seven of nine OTUs were from the Bacteroidetes, and the rest of the OTUs were from Firmicutes. These core gut microbiota OTUs were reported to be pivotal to the host homeostasis in healthy mice of other studies (Xiao et al., 2015), suggesting that the mice with different treatments in our study might still keep the homeostasis of gut microbiota (Wang et al., 2019).

On the other hand, random forest models were constructed to reveal the effect of donor or diet fiber on the bacteria genera. When a random forest model was constructed to classify the donor effect of FMT, Anaeroplasma showed the highest MDA value in the random forest model, suggesting that FMT of the different donors had a more significant effect on the Anaeroplasma than other genera in the gut. A higher abundance of Anaeroplasma in mice FMT from domestic pigs was observed than that in mice FMT from the wild pig. The higher relative abundance of Anaeroplasma has been reported to be positively corrected with the digestibility in pigs (Niu et al., 2015). Studies suggested that mammalian gut bacterial genomes adapted to environmental changes imposed by their mammalian host (Koskella and Brockhurst, 2014; Zhao et al., 2019). Although the wild pig belongs to the same species as domestic pigs, the wild pig is suited to the wild habitat, and natural genetic selection has been driven by selection pressures of challenging environments, whereas phenotypes in commercial systems such as growth/production orientated are not necessary (Rivero et al., 2019). Higher relative abundance of Anaeroplasma in mice FMT from domestic pig might be results of the domestic pig that adapted for the growth/production.

The bacteria unclassified_o_Bacteroidales and Odoribacter were found to exist in the mice FMT from the domestic pig, whereas not detected in mice FMT from wild pig. Odoribacter, belonging to the order Bacteroidales, is a common member both in the human and pig gut microbiota and is capable of butyrate production via lysine fermentation and succinate reduction (Lim et al., 2017; Rychlik, 2020). Lack of Odoribacter suggesting differential ways in supplementary of SCFAs might exist in the wild pig and the mice FMT from the wild pig. Moreover, Akkermansia with the highest linear discriminant analysis score was observed to be enriched in WF mice, which has been reported to convert dietary fiber into acetate, propionate, and butyrate in the gut (Chambers et al., 2018; Xu et al., 2020). Although the relative abundance of SCFA-producing genera Odoribacter was depleted in mice FMT from the wild pig, a higher relative abundance of Akkermansia coupled with high dietary fiber in WF mice might be an alternative way to supply the SCFAs. The FMT from different donors contributed to the differential of specific genera in the gut of mice, although the mice received dietary fiber at different content. In return, specific genera have been altered by the differential dietary fiber contents rather than FMT, including unclassified_o_Desulfovibrionales, Butyricimonas, Clostridium IV, and Eubacterium. Higher relative abundance of unclassified_o_Desulfovibrionales and Butyricimonas were observed in the gut of mice received with lower dietary fiber. Bacteria from the order Desulfovibrionales were usually pro-inflammatory (Rajilić-Stojanović and de Vos, 2014) through colonization, utilization, and degradation of the colonic mucin layer (Earley et al., 2015; Bishehsari et al., 2018). Consistent with previous studies, Butyricimonas, Clostridium XI, and Eubacterium were more abundant in the gut with a low-fiber diet in mice or adults (Hamilton et al., 2015; Lin et al., 2018; Tran et al., 2019). A lower OOB rate in the model constructed in fiber than that in the model donor was observed, suggesting that the intervention of dietary fiber might play a more critical role in shaping the gut microbiota of mice.

Besides the bacteria independent from FMT or dietary fiber, LEfSe analysis revealed the bacteria genera influenced by FMT together with dietary fiber in mice. Enrichment of Akkermansia was observed in the gut of mice FMT from wild pig and received with higher dietary fiber. Akkermansia is a mucin degrader that converts mucin to SCFAs that may mediate the immunoregulatory effects (Derrien et al., 2004) and has been reported to be an emerging probiotic that can be enhanced through dietary interventions (Zhou, 2017). Parabacteroides was also observed to be enriched in WF mice and prominently found in healthy individuals’ gut (Xu et al., 2007). A previous study showed that oral administration of the strains from Parabacteroides could utilize polysaccharides, induce expression of interleukin-10, and helps maintain intestinal integrity, thus improve gut barrier function in mice (Wu et al., 2019). Enrichment of potential probiotics such as Akkermansia and Parabacteroides in WF mice suggests that the FMT from different donors could shape the bacteria composition, and intervention of dietary fiber could amplify this effect, thus contributed to the improvement of gut health. Nevertheless, we acknowledge that the antibiotic treatment could influence the effects of both FMT and dietary intervention in some of the results observed, especially the lower alpha diversity in FMT mice, although minor effects of antibiotic pretreatment in FMT were reported (Freitag et al., 2019). Although highly efficacious for the FMT in the treatment of dysfunction in several diseases were observed (Nowak et al., 2019; Chinna Meyyappan et al., 2020), 10–20% of recipients fail to achieve cure after a single FMT (Fischer et al., 2016; Lynch et al., 2019), our study demonstrated the diet intervention might contribute to the efficiency of FMT.

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 in the article/Supplementary Material.

The animal study was reviewed and approved by the Animal Protection and Use Committee of Zhejiang University.

HW designed the experiments. JC, YZ, YM, and ZD performed the experiments. HW, YZ, JC, and JL analyzed the data. HW and YZ wrote and revised the main manuscript. All authors read and approved the final manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.