Dietary protein source strongly alters gut microbiota composition and function

Blakeley-Ruiz, J. Alfredo; Bartlett, Alexandria; McMillan, Arthur S; Awan, Ayesha; Vanhoy Walsh, Molly; Meyerhoffer, Alissa K; Vintila, Simina; Maier, Jessie L; Richie, Tanner; Theriot, Casey M; Kleiner, Manuel

doi:10.1101/2024.04.04.588169

Cited by 3 publications

(2 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These included mucin 5B and alpha-1-acid glycoprotein in egg white and cell wall proteins in yeast. We previously showed that egg white and yeast protein diets impact the glycan metabolism of the gut microbiota 11,46 and now our results suggest that these specific glycoproteins may be involved in affecting microbiota glycan metabolism. In summary, our results show that dietary proteins from various sources with specific functional and structural features relevant to host physiology and microbial metabolism were differentially processed in the gut.…”

Section: Discussionsupporting

confidence: 63%

“…While the exact mechanisms by which dietary protein from various sources impacts the host are not well understood, interactions between undigested dietary protein and the intestinal microbiota are thought to play a key role 7,8 . Specific dietary components, including dietary protein and fiber, have been shown to impact the composition and function of the gut microbiota [9][10][11] . Dietary proteins that escape host digestion can be converted by the gut microbiota to produce metabolites that impact host health, such as beneficial short-chain fatty acids or proinflammatory ammonia, amines, and hydrogen sulfide 7,12 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dietary protein from different sources escapes host digestion and is differentially modified by the microbiota

Awan,

Bartlett,

Blakeley-Ruiz

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Protein is an essential macronutrient and variations in its source and quantity have been shown to impact long-term health outcomes. Differential health impacts of dietary proteins from various sources are likely driven by differences in their digestibility by the host and subsequent availability to the intestinal microbiota. However, our current understanding regarding the fate of dietary proteins from different sources in the gut, specifically how component proteins within these sources interact with the host and the gut microbiota, is limited. To determine which dietary proteins are efficiently digested by the host and which proteins escape host digestion and are used by the gut microbiota, we used high-resolution mass spectrometry to quantify the proteins that make up different dietary protein sources before and after digestion in germ-free and conventionally raised mice. Contrary to expectation, we detected proteins from all sources in fecal samples of both germ-free and conventional mice suggesting that even protein sources with a high digestive efficiency make it in part to the colon where they can serve as a substrate for the microbiota. Additionally, we found clear patterns where specific component proteins of the dietary protein sources were used as a preferred substrate by the microbiota or were not as accessible to the microbiota. We found that specific proteins with functions that could impact host health and physiology were differentially enriched in germ-free or conventionally raised mice. These findings reveal large differences in the fate of dietary protein from various sources in the gut that could explain some of their differential health impacts.

show abstract

Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Dietary protein from different sources escapes host digestion and is differentially modified by the microbiota

Awan,

Bartlett,

Blakeley-Ruiz

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages

Cortés-Martín,

Buttimer,

Maier

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Bacteriophages (phages) and bacteria within the gut microbiome persist in long-term stable coexistence. These interactions are driven by eco-evolutionary dynamics, where bacteria employ a variety of mechanisms to evade phage infection, while phages rely on counterstrategies to overcome these defences. Among the most abundant phages in the gut are the crAss-like phages that infect members of the Bacteroidales, in particular Bacteroides. In this study, we explored some of the mechanisms enabling the co-existence of four phage-Bacteroidales host pairs in vitro using a multi-omics approach (transcriptomics, proteomics and metabolomics). These included three Bacteroides species paired with three crAss-like phages (Bacteroides intestinalis and фcrAss001, Bacteroides xylanisolvens and фcrAss002, and an acapsular mutant of Bacteroides thetaiotaomicron with DAC15), and Parabacteroides distasonis paired with the siphovirus фPDS1. Results: We show that phase variation of individual capsular polysaccharides (CPSs) is the primary mechanism promoting phage co-existence in Bacteroidales, but this is not the only strategy. Alternative resistance mechanisms, while potentially less efficient than CPS phase variation, can be activated to support bacterial survival by regulating gene expression and resulting in metabolic adaptations, particularly in amino acid degradation pathways. These mechanisms, also likely regulated by phase variation, enable bacterial populations to persist in the presence of phages, and vice versa. An acapsular variant of B. thetaiotaomicron demonstrated broader transcriptomic, proteomic, and metabolomic changes, supporting the involvement of additional resistance mechanisms beyond CPS variation. Conclusions: This study advances our understanding of long-term phage-host interaction, offering insights into the long-term persistence of crAss-like phages and extending these observations to other phages, such as фPDS1. Knowledge of the complexities of phage-bacteria interactions is essential for designing effective phage therapies and improving human health through targeted microbiome interventions.

show abstract

Stable isotope fingerprinting can directly link intestinal microorganisms with their carbon source and captures diet-induced substrate switchingin vivo

Mordant,

Blakeley-Ruiz,

Kleiner

2024

Preprint

View full text Add to dashboard Cite

Diet has strong impacts on the composition and function of the gut microbiota with implications for host health. Therefore, it is critical to identify the dietary components that support growth of specific microorganismsin vivo. We used protein-based stable isotope fingerprinting (Protein-SIF) to link microbial species in gut microbiota to their carbon sources by measuring each microbe’s natural13C content (δ13C) and matching it to the13C content of available substrates. We fed gnotobiotic mice, inoculated with a 13 member microbiota, diets in which the13C content of all components was known. We varied the source of protein, fiber or fat to observe13C signature changes in microbial consumers of these substrates. We observed significant changes in the δ13C values and abundances of specific microbiota species, as well as host proteins, in response to changes in13C signature or type of protein, fiber, and fat sources.Using this approach we were able to show that upon switching dietary source of protein, fiber, or fat (1) some microbial species continued to obtain their carbon from the same dietary component (e.g., protein); (2) some species switched their main substrate type (e.g., from protein to carbohydrates); and (3) some species might derive their carbon through foraging on host compounds. Our results demonstrate that Protein-SIF can be used to identify the dietary-derived substrates assimilated into proteins by microbes in the intestinal tract; this approach holds promise for the analysis of microbiome substrate usage in humans without the need of substrate labeling.SignificanceThe gut microbiota plays a critical role in the health of animals including humans, influencing metabolism, the immune system, and even behavior. Diet is one of the most significant factors in determining the function and composition of the gut microbiota, but our understanding of how specific dietary components directly impact individual microbes remains limited. We present the application of an approach that measures the carbon isotope “fingerprint” of proteins in biological samples. This fingerprint is similar to the fingerprint of the substrate used to make the proteins. We describe how we used this approach in mice to determine which dietary components specific intestinal microbes use as carbon sources to make their proteins. This approach can directly identify components of an animal’s diet that are consumed by gut microbes.

show abstract

Dietary protein source strongly alters gut microbiota composition and function

Cited by 3 publications

References 89 publications

Dietary protein from different sources escapes host digestion and is differentially modified by the microbiota

Dietary protein from different sources escapes host digestion and is differentially modified by the microbiota

Adaptations in gut Bacteroidales facilitate stable co-existence with their lytic bacteriophages

Stable isotope fingerprinting can directly link intestinal microorganisms with their carbon source and captures diet-induced substrate switchingin vivo

Contact Info

Product

Resources

About