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Despite numerous studies on the health benefits of the rare sugar allulose, its effects on intestinal mucosal morphology and function are unclear. We therefore first determined its acute effects on the small intestinal transcriptome using DNA microarray analysis following intestinal allulose, fructose and glucose perfusion in rats. Expression levels of about 8-fold more genes were altered by allulose compared to fructose and glucose perfusion, suggesting a much greater impact on the intestinal transcriptome. Subsequent pathway analysis indicated that nutrient transport, metabolism, and digestive system development were markedly upregulated, suggesting allulose may acutely stimulate these functions. We then evaluated whether allulose can restore rat small intestinal structure and function when ingested orally following total parenteral nutrition (TPN). We also monitored allulose effects on blood levels of glucagon-like peptides (GLP) 1 and 2 in TPN rats and normal mice. Expression levels of fatty acid binding and gut barrier proteins were reduced by TPN but rescued by allulose ingestion, and paralleled GLP-2 secretion potentially acting as the mechanism mediating the rescue effect. Thus, allulose can potentially enhance disrupted gut mucosal barriers as it can more extensively modulate the intestinal transcriptome relative to glucose and fructose considered risk factors of metabolic disease. 

Abstract Background Lactobacillus rhamnosus GG (LGG) is the most widely used probiotic, but the mechanisms underlying its beneficial effects remain unresolved. Previous studies typically inoculated LGG in hosts with established gut microbiota, limiting the understanding of specific impacts of LGG on host due to numerous interactions among LGG, commensal microbes, and the host. There has been a scarcity of studies that used gnotobiotic animals to elucidate LGG-host interaction, in particular for gaining specific insights about how it modifies the metabolome. To evaluate whether LGG affects the metabolite output of pathobionts, we inoculated with LGG gnotobiotic mice containing Propionibacterium acnes, Turicibacter sanguinis, and Staphylococcus aureus (PTS). Results 16S rRNA sequencing of fecal samples by Ion Torrent and MinION platforms showed colonization of germ-free mice by PTS or by PTS plus LGG (LTS). Although the body weights and feeding rates of mice remained similar between PTS and LTS groups, co-associating LGG with PTS led to a pronounced reduction in abundance of P. acnes in the gut. Addition of LGG or its secretome inhibited P. acnes growth in culture. After optimizing procedures for fecal metabolite extraction and metabolomic liquid chromatography-mass spectrometry analysis, unsupervised and supervised multivariate analyses revealed a distinct separation among fecal metabolites of PTS, LTS, and germ-free groups. Variables-important-in-projection scores showed that LGG colonization robustly diminished guanine, ornitihine, and sorbitol while significantly elevating acetylated amino acids, ribitol, indolelactic acid, and histamine. In addition, carnitine, betaine, and glutamate increased while thymidine, quinic acid and biotin were reduced in both PTS and LTS groups. Furthermore, LGG association reduced intestinal mucosal expression levels of inflammatory cytokines, such as IL-1α, IL-1β and TNF-α. Conclusions LGG co-association had a negative impact on colonization of P. acnes , and markedly altered the metabolic output and inflammatory response elicited by pathobionts. 

Synopsis We argue that the current environmental changes stressing the Earth’s biological systems urgently require study from an integrated perspective to reveal unexpected, cross-scale interactions, particularly between microbes and macroscale phenomena. Such interactions are the basis of a mechanistic understanding of the important connections between deforestation and emerging infectious disease, feedback between ecosystem disturbance and the gut microbiome, and the cross-scale effects of environmental pollutants. These kinds of questions can be answered with existing techniques and data, but a concerted effort is necessary to better coordinate studies and data sets from different disciplines to fully leverage their potential. 

ABSTRACT Background High intakes of fructose are associated with metabolic diseases, including hypertriglyceridemia and intestinal tumor growth. Although small intestinal epithelia consist of many different cell types, express lipogenic genes, and convert dietary fructose to fatty acids, there is no information on the identity of the cell type(s) mediating this conversion and on the effects of fructose on lipogenic gene expression. Objectives We hypothesized that fructose regulates the intestinal expression of genes involved in lipid and apolipoprotein synthesis, that regulation depends on the fructose transporter solute carrier family 2 member a5 [Slc2a5 (glucose transporter 5)] and on ketohexokinase (Khk), and that regulation occurs only in enterocytes. Methods We compared lipogenic gene expression among different organs from wild-type adult male C57BL mice consuming a standard vivarium nonpurified diet. We then gavaged twice daily for 2.5 d fructose or glucose solutions (15%, 0.3 mL per mouse) into wild-type, Slc2a5-knockout (KO), and Khk-KO mice with free access to the nonpurified diet and determined expression of representative lipogenic genes. Finally, from mice fed the nonpurified diet, we made organoids highly enriched in enterocyte, goblet, Paneth, or stem cells and then incubated them overnight in 10 mM fructose or glucose. Results Most lipogenic genes were significantly expressed in the intestine relative to the kidney, liver, lung, and skeletal muscle. In vivo expression of Srebf1, Acaca, Fasn, Scd1, Dgat1, Gk, Apoa4, and Apob mRNA and of Scd1 protein increased (P < 0.05) by 3- to 20-fold in wild-type, but not in Slc2a5-KO and Khk-KO, mice gavaged with fructose. In vitro, Slc2a5- and Khk-dependent, fructose-induced increases, which ranged from 1.5- to 4-fold (P < 0.05), in mRNA concentrations of all these genes were observed only in organoids enriched in enterocytes. Conclusions Fructose specifically stimulates expression of mouse small intestinal genes for lipid and apolipoprotein synthesis. Secretory and stem cells seem incapable of transport- and metabolism-dependent lipogenesis, occurring only in absorptive enterocytes.