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							| Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007



	

				
						
 
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																Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007
										

				


				
				
					
					
						
																					
				
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					Vol. 15 No. 12 (2025): December 2025
				
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									Research Articles
							
		



	
		  	 

		
	
		Ultra-low-dose lactulose modulates the gut microbiota in healthy adults: A double-blind, randomized, placebo-controlled crossover trial
	


	
	
		

							
					Authors

						
							
								Ryo Sakiyama
							
																																		
	
							
								Seiya Miyashita
							
																																		
	
							
								Manabu Nakano
							
																																		
	
							
								Miyuki Tanaka
							
																																		


				
			
																	
					
												DOI:
					

					
						
							https://doi.org/10.31989/ffhd.v15i12.1838
						
					
				
			

						
										
					Abstract

					Background: Gut health, particularly the composition and function of the gut microbiota, is increasingly recognized as essential for overall well-being. Non-digestible oligosaccharides are established prebiotics that stimulate beneficial gut bacteria; however, excessive intake may cause gastrointestinal discomfort. This study aimed to determine the minimum effective dose of lactulose using 16S rRNA gene sequencing to support safe and sustainable dietary applications.

Methods: In a double-blind, randomized, placebo-controlled crossover trial, 100 healthy Japanese adults received lactulose (500 mg/day) or placebo for 28 days, separated by a 14-day washout period. The relative abundance of Bifidobacterium was analyzed using a linear mixed model with centered log-ratio transformation.

Results: As a result of the analyses conducted on the PPS (Per Protocol Set, n = 78) and FAS (Full Analysis Set, n = 99), lactulose intake significantly increased the relative abundance of Bifidobacterium. Overall alpha diversity remained unchanged, although participants with low baseline alpha diversity enterotypes showed a trend toward restoration of alpha diversity. No adverse events or gastrointestinal symptoms, such as bloating or diarrhea, were observed, confirming the safety of lactulose.

Conclusions: These findings provide novel evidence that even minimal doses of lactulose can beneficially modulate the gut microbiota, notably by increasing the relative abundance of Bifidobacterium without inducing laxative effects. Ultra-low-dose lactulose may serve as a practical and safe functional food ingredient to support long-term gut health, and continued research on its incorporation into functional food matrices will be important.

Trial registration: The study protocol was registered with UMIN-CTR (ID: UMIN000055862).

Keywords: Lactulose; Prebiotics; Bifidobacterium; Improving gut microbiota, Gastrointestinal health

				
			
			

						
																																								
						
		


		

						
										
					
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																			2025-12-09
																	

				
							

			
						
										

											
							
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									Vol. 15 No. 12 (2025): December 2025
								
							

						
					
											
							
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								Research Articles
							

						
					
									

			
						
										
					
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																										Copyright (c) 2025 Ryo Sakiyama, Seiya Miyashita, Manabu Nakano, Miyuki Tanaka

														This work is licensed under a Creative Commons Attribution 4.0 International License.

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This license permits unrestricted use, distribution, and reproduction in any medium, including commercial use, provided the original author(s) and source are properly credited. Authors may post and share their published work freely, provided that the original publication in this journal is acknowledged.

By submitting to this journal, authors confirm that their manuscripts are original, not under consideration elsewhere, and that they hold the necessary rights to grant this license. The Functional Food Center encourages open scientific exchange and allows derivative and extended works, provided attribution to the original publication is maintained.

				

			
			

		

	




	




	


							



	

	

					
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