Biology subjects

Surana, N. K.

Publications and source records attributed to Surana, N. K..

4 recordsLinked to original sources

bioRxiv2024

A commensal-derived sugar protects against metabolic disease

Obesity is a worsening global epidemic that is regulated by the microbiota through unknown bacterial factors. We discovered a human commensal bacterium, Clostridium immunis, that treats obesity by secreting a phosphocholine-modified exopolysaccharide. Loss- and gain-of-function bacterial mutants involving the phosphocholine biosynthesis locus (licABC) revealed the phosphocholine moiety is critically required to protect against metabolic disease. This C. immunis exopolysaccharide decreases small-intestinal and visceral fat levels of IL-22, which increases metabolic activity specifically in visceral adipose tissue. Importantly, phosphocholine biosynthesis genes are less abundant in humans with obesity or hypertriglyceridemia, findings that suggest the role of bacterial phosphocholine is conserved across mice and humans. These results define a bacterial molecule--and its key structural motif--that provides immunometabolic control of obesity. More broadly, they highlight a clinically translatable strategy to reduce visceral fat.

microbiology↗

bioRxiv2024

Interplay between particle size and microbial ecology in the gut microbiome

Physical particles can serve as critical abiotic factors that structure the ecology of microbial communities. For non-human vertebrate gut microbiomes, fecal particle size (FPS) has been known to be shaped by chewing efficiency and diet. However, little is known about what drives FPS in the human gut. Here, we analyzed FPS by laser diffraction across a total of 76 individuals and found FPS to be strongly individualized. Surprisingly, a behavioral intervention with 41 volunteers designed to increase chewing efficiency did not impact FPS. Dietary patterns could also not be associated with FPS. Instead, we found evidence that mammalian and human gut microbiomes shaped FPS. Fecal samples from germ-free and antibiotic-treated mice exhibited increased FPS relative to colonized mice. In humans, markers of longer transit time were correlated with smaller FPS. Gut microbiota diversity and composition were also associated with FPS. Finally, ex vivo culture experiments using human fecal microbiota from distinct donors showed that differences in microbiota community composition can drive variation in particle size. Together, our results support an ecological model in which the human gut microbiome plays a key role in reducing the size of food particles during digestion, and that the microbiomes of individuals vary in this capacity. These new insights also suggest FPS in humans to be governed by processes beyond those found in other mammals and emphasize the importance of gut microbiota in shaping their own abiotic environment.

microbiology↗

bioRxiv2024

Commensal bacteria inhibit viral infections via a tryptophan metabolite

Clinical outcomes following viral exposures exhibit substantial interindividual variability. Although developing evidence suggests commensal bacteria modulate viral infections, the specific bacteria and mechanisms remain underexplored. Here we define a pathway by which viral infections are inhibited by specific tryptophan-catabolizing bacteria. Using HIV as a model, we bioinformatically associated and experimentally validated several bacterial species that inhibited viral replication. This activity required the aromatic amino acid aminotransferase (ArAT) to metabolize tryptophan into 3-indolelactic acid, which agonizes the aryl hydrocarbon receptor (AhR). Given that AhR regulates multiple viral infections, we found that commensal bacteria also inhibit cytomegalovirus (CMV) in an ArAT-dependent manner. Finally, we confirmed that ArAT is associated with protection against disease outcomes in three distinct human cohorts at-risk for HIV, CMV, or symptomatic COVID-19. Taken together, our results provide mechanistic insight into how commensal bacteria impact viral infections, thereby adding to an emerging field focused on host-commensal-virus interactions.

microbiology↗

bioRxiv2019

Gut-innervating nociceptor neurons protect against enteric infection by modulating the microbiota and Peyer’s patch microfold cells

Gut-innervating nociceptor sensory neurons respond to noxious/tissue-damaging stimuli by initiating protective responses and releasing mediators that regulate tissue inflammation, gastrointestinal secretion, and motility. The role of nociceptors in host defense against enteric pathogens is unclear. Here, we found that gut-extrinsic nociceptor neurons are critical in protecting the host against Salmonella typhimurium (STm) infection. Nociceptors responded to STm by releasing the neuropeptide calcitonin gene-related peptide (CGRP). Targeted depletion of Nav1.8 and TRPV1 neurons from gut-extrinsic dorsal root ganglia and vagal ganglia increased STm colonization, invasion, and dissemination. Nociceptors regulated the gut microbiota at homeostasis, specifically segmented filamentous bacteria (SFB) levels in the ileum, which protected against STm by colonization resistance. Nociceptors also regulated the density of microfold epithelial cells in the Peyers patch via CGRP to limit points of entry for STm invasion into host tissues. Understanding how host sensory neurons crosstalk with pathogenic bacteria may impact treatments for enteric infections.\n\nHIGHLIGHTSO_LINav1.8 and TRPV1 nociceptors defend against Salmonella typhimurium (STm) infection\nC_LIO_LINociceptors shape the gut microbiota and SFB levels which resist pathogen colonization\nC_LIO_LINociceptors suppress Peyers patch microfold cell density to limit pathogen invasion\nC_LIO_LINeurons sense STm and release CGRP to modulate microfold cells and host defense\nC_LI

immunology↗